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        "titulo" => "Prognostic impact of metformin in patients with type 2 diabetes mellitus and acute heart failure&#58; Combined analysis of the EAHFE and RICA registries"
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Diagrama de flujo de los pacientes&#46; DM&#58; diabetes mellitus&#59; EAHFE&#58; <span class="elsevierStyleItalic">Epidemiology of Acute Heart Failure in Emergency Departments</span>&#59; RICA&#58; Registro Nacional de Pacientes con Insuficiencia Cardiaca&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La prevalencia e incidencia de la insuficiencia cardiaca &#40;IC&#41; y la diabetes mellitus &#40;DM&#41; han aumentado de forma progresiva en la &#250;ltima d&#233;cada<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; La DM tipo 2 se considera un factor independiente para el desarrollo de IC<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">3</span></a> y&#44; a su vez&#44; se asocia a un peor pron&#243;stico en IC<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">4&#44;5</span></a>&#46; En los pacientes hospitalizados por IC&#44; la DM se asocia con mayor estancia hospitalaria y tasa de reingreso<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">6&#44;7</span></a>&#44; as&#237; como con mayor comorbilidad asociada<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">7&#44;8</span></a>&#46; Sin embargo&#44; el papel de la DM en la mortalidad hospitalaria y a largo plazo en pacientes con IC contin&#250;a siendo controvertido<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">9&#44;10</span></a>&#46; Los datos del Registro Nacional de Pacientes con Insuficiencia Cardiaca &#40;RICA&#41; revelan que los pacientes con DM tipo 2 presentan mayor tasa de reingresos por IC y mortalidad a largo plazo frente a los que no padecen esta enfermedad&#44; si bien la mortalidad intrahospitalaria parece igualarse en ambos grupos<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">El tratamiento neurohormonal disponible en los &#250;ltimos a&#241;os ha mejorado el pron&#243;stico de los pacientes con IC<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">11</span></a>&#44; y 2 grupos de f&#225;rmacos hipoglucemiantes&#44; los inhibidores del cotransportador sodio-glucosa tipo 2 &#40;iSGLT2&#41; y los agonistas del receptor de GLP-1 &#40;arGLP-1&#41; han demostrado beneficios a nivel cardiovascular tanto en pacientes con DM tipo 2 como en los que no la presentan<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">12&#8211;27</span></a>&#46; La &#250;ltima gu&#237;a europea de DM<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">28</span></a> recomienda estos f&#225;rmacos como tratamiento de inicio en los pacientes de riesgo cardiovascular alto o muy alto y que no est&#233;n recibiendo todav&#237;a metformina&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">La metformina es un f&#225;rmaco cl&#225;sico dentro del tratamiento de la DM tipo 2<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">29&#44;30</span></a>&#46; Por su evidencia en el descenso en las complicaciones macrovasculares<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">31</span></a>&#44; las gu&#237;as lo recomiendan como primera opci&#243;n de tratamiento en la mayor&#237;a de los pacientes&#46; Sin embargo&#44; su efecto en el pron&#243;stico de los pacientes con IC todav&#237;a no ha sido investigado&#46; El objetivo principal de este estudio fue analizar si los pacientes con DM e IC aguda que reciben tratamiento con metformina en el momento del alta presentan mejor pron&#243;stico al a&#241;o de seguimiento&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Dise&#241;o y fuente de los datos</span><p id="par0020" class="elsevierStylePara elsevierViewall">Planteamos un estudio observacional de cohortes prospectivo en el que combinamos datos de pacientes incluidos en los 2 principales registros espa&#241;oles de IC&#58; el registro <span class="elsevierStyleItalic">Epidemiology of Acute Heart Failure in Emergency Departments</span> &#40;EAHFE&#41; y el RICA&#46; Se trata de un estudio de efectividad que pretende valorar en una poblaci&#243;n real el uso de la metformina y su impacto pron&#243;stico al a&#241;o de seguimiento&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">El registro EAHFE es un estudio de cohorte multic&#233;ntrico&#44; de car&#225;cter anal&#237;tico no intervencionista con seguimiento prospectivo<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">32&#8211;34</span></a>&#44; promovido por el Grupo de Trabajo de Insuficiencia Cardiaca de la Sociedad Espa&#241;ola de Medicina de Urgencias y Emergencias&#46; Participan un total de 45 servicios de urgencias hospitalarios &#40;SUH&#41; espa&#241;oles&#44; que han incorporado 18&#46;370 pacientes diagnosticados de IC aguda entre 2007 y 2018&#44; en 6 periodos de selecci&#243;n de 1-2 meses cada 2 o 3 a&#241;os&#46; Este registro no incluye ninguna intervenci&#243;n planificada ni modifica la atenci&#243;n recibida por el m&#233;dico asistencial&#44; la cual est&#225; basada en las gu&#237;as de pr&#225;ctica cl&#237;nica &#40;GPC&#41; y los protocolos de cada centro hospitalario&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">El RICA es un estudio de cohorte prospectivo multic&#233;ntrico<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">35&#44;36</span></a> del Grupo de Trabajo Insuficiencia Cardiaca y Fibrilaci&#243;n Auricular de la Sociedad Espa&#241;ola de Medicina Interna&#46; Participan 52 centros p&#250;blicos y privados de Espa&#241;a y est&#225; activo desde 2008&#46; En &#233;l se incluyen pacientes &#250;nicos consecutivos&#44; mayores de 50 a&#241;os&#44; con diagn&#243;stico de IC al alta hospitalaria tras un episodio de descompensaci&#243;n de IC de nueva aparici&#243;n&#44; de acuerdo con la definici&#243;n de las gu&#237;as de la Sociedad Europea de Cardiolog&#237;a vigentes<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">37</span></a>&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Poblaci&#243;n de estudio</span><p id="par0035" class="elsevierStylePara elsevierViewall">Se incluyeron todos los pacientes del RICA hasta el a&#241;o 2018 y las poblaciones de EAHFE-5 &#40;periodo de inclusi&#243;n del 1 de enero al 29 de febrero de 2016&#44; con participaci&#243;n de 30 SUH&#41; y EAHFE-6 &#40;periodo de inclusi&#243;n del 1 de febrero al 31 de marzo de 2018&#44; con participaci&#243;n de 34 SUH&#41;&#44; en las cuales se recogieron datos relacionados con el tratamiento de la DM&#46; Tras realizar los tr&#225;mites pertinentes en cuanto a permisos de manejo de datos para ambos registros&#44; se realiz&#243; una base de datos conjunta manteniendo todas las variables comunes y eliminando las no coincidentes&#44; para favorecer el an&#225;lisis unificado de ambas poblaciones de estudio&#46; Dentro de este grupo poblacional seleccionamos como poblaci&#243;n a estudio los pacientes con DM tipo 2 &#40;si constaba como diagn&#243;stico previo&#44; tomaban f&#225;rmacos hipoglucemiantes o si su concentraci&#243;n de hemoglobina glucosilada al ingreso era<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>6&#44;5&#37;&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Variables</span><p id="par0040" class="elsevierStylePara elsevierViewall">Se recogieron variables cl&#237;nicas y de tratamiento que han sido definidas en otros art&#237;culos previos del RICA<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">4</span></a> y el EAHFE<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">38</span></a>&#46; Se realiz&#243; un seguimiento a 12 meses desde el alta hospitalaria del episodio &#237;ndice de IC aguda&#44; y se registr&#243; la mortalidad al a&#241;o por cualquier causa mediante consulta de la historia cl&#237;nica o contacto directo&#44; y en caso necesario se verific&#243; en el registro de la Seguridad Social&#44; donde los pacientes fallecidos constan baja al d&#237;a siguiente del deceso&#46; Se excluyeron del estudio los pacientes que fallecieron en el hospital durante el episodio &#237;ndice&#46; Para calcular la variable de tiempo de seguimiento&#44; se dispone de la fecha de finalizaci&#243;n del estudio &#40;correspondiente al a&#241;o de seguimiento desde el episodio &#237;ndice&#41;&#44; la fecha de exitus o la fecha de p&#233;rdida de seguimiento en aquellos casos en que ocurri&#243; la p&#233;rdida de seguimiento antes del a&#241;o &#40;fecha de censura para el estudio de supervivencia&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Consideraciones &#233;ticas</span><p id="par0045" class="elsevierStylePara elsevierViewall">El protocolo del RICA fue aprobado por el Comit&#233; de &#201;tica del Hospital Universitario Reina Sof&#237;a de C&#243;rdoba &#40;Espa&#241;a&#41; y el del registro EAHFE por el del Hospital Universitario Central de Asturias &#40;Oviedo&#44; Espa&#241;a&#41;&#46; Los n&#250;meros de referencia para las fases 5 y 6 son 160&#47;15 y 205&#47;17&#44; respectivamente&#46; Los datos fueron introducidos en bases de datos anonimizadas y han sido manejados de acuerdo con el RD 1720&#47;2007 que desarrolla la Ley Org&#225;nica 15&#47;1999&#44; de 13 de diciembre&#44; de Protecci&#243;n de Datos de Car&#225;cter Personal<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">4&#44;35&#44;36</span></a>&#46; El estudio se llev&#243; a cabo en estricto cumplimiento de los principios &#233;ticos de la Declaraci&#243;n de Helsinki&#46; Al tratarse de estudios observacionales de cohortes&#44; ambos registros siguieron las pautas STROBE para este m&#233;todo&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">An&#225;lisis estad&#237;stico</span><p id="par0050" class="elsevierStylePara elsevierViewall">Las variables cualitativas han sido expresadas como frecuencia y porcentaje&#46; Las variables cuantitativas continuas se muestran como media y desviaci&#243;n est&#225;ndar tras realizar la prueba de an&#225;lisis de normalidad de Kolmogorov-Smirnov&#46; El an&#225;lisis comparativo bivariante se realiz&#243; mediante la prueba de ji cuadrado cuando eran 2 pruebas cat&#233;goricas&#44; y mediante ANOVA para la comparaci&#243;n de variables cuantitativas de m&#225;s de 2 grupos&#46; Para el an&#225;lisis de mortalidad se realizaron las curvas de supervivencia de Kaplan-Meier y el test de Log Rank&#46; Se ha llevado a cabo un an&#225;lisis multivariante de riesgos proporcionales de regresi&#243;n de Cox por el m&#233;todo hacia atr&#225;s condicional para las variables que en el an&#225;lisis univariante mostraban una relaci&#243;n significativamente estad&#237;stica con la probabilidad de muerte&#46; El riesgo asociado a fallecer por cualquier causa en los pacientes en tratamiento se expres&#243; como riesgo relativo &#40;RR&#41; con su intervalo de confianza del 95&#37; &#40;IC 95&#37;&#41; respecto a los pacientes que no recib&#237;an metformina&#46; Se ha realizado un <span class="elsevierStyleItalic">forest plot</span> para valorar c&#243;mo se comporta la metformina en diferentes subpoblaciones de pacientes&#46; Todos los an&#225;lisis estad&#237;sticos se realizaron con SPSS&#174; 26&#46;0 &#40;IBM&#44; Chicago&#44; IL&#44; EE&#46; UU&#46;&#41;&#46; La significaci&#243;n estad&#237;stica se estableci&#243; como p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 o si el IC 95&#37; de la <span class="elsevierStyleItalic">hazard ratio</span> no inclu&#237;a el valor 1&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Resultados</span><p id="par0055" class="elsevierStylePara elsevierViewall">Del total de 10&#46;122 pacientes incluidos al aunar las bases de datos EAHFE y RICA&#44; se incluyeron 4&#46;403 pacientes con DM tipo 2&#44; lo que supone el 43&#44;5&#37; del total&#46; El an&#225;lisis de subgrupos se realiz&#243; en funci&#243;n de si recib&#237;an o no tratamiento con metformina al alta del episodio &#237;ndice de descompensaci&#243;n &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se describen las caracter&#237;sticas del grupo de pacientes con DM tipo 2 y de ambos subgrupos&#46; Los 1&#46;453 pacientes que reciben tratamiento con metformina tras el alta hospitalaria representan un 33&#37; del total de los pacientes con DM tipo 2&#46; Estos pacientes son m&#225;s j&#243;venes &#40;77 versus 79 a&#241;os&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y presentan menor comorbilidad&#44; siendo significativamente inferior la prevalencia de cardiopat&#237;a isqu&#233;mica &#40;29 versus 34&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;011&#41; y enfermedad renal cr&#243;nica &#40;24 versus 50&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; Adem&#225;s&#44; presentan mejor situaci&#243;n funcional&#44; con menor porcentaje de clase funcional NYHA III-IV &#40;35 versus 29&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y mayor puntuaci&#243;n en el &#237;ndice de Barthel &#40;84 versus 79&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; Los f&#225;rmacos que reciben ambos grupos respecto al tratamiento de IC est&#225;n expuestos en la tabla y respecto al tratamiento de DM&#44; el grupo de metformina presenta con mayor frecuencia otros antidiab&#233;ticos orales asociados y menor porcentaje de insulinizaci&#243;n &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">En el seguimiento a 12 meses &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#44; se observa que el grupo de pacientes con metformina al alta presenta una mortalidad significativamente inferior &#40;22 versus 32&#37;&#59; test de Log Rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Se realiza an&#225;lisis univariante y multivariante respecto a la mortalidad al a&#241;o de seguimiento &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; En el an&#225;lisis ajustado&#44; los pacientes que presentan mayor mortalidad al a&#241;o de seguimiento tienen mayor edad &#40;RR 1&#44;025&#59; IC 95&#37; 1&#44;018-1&#44;033&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y presentan con mayor frecuencia comorbilidad asociada&#44; como cardiopat&#237;a isqu&#233;mica &#40;RR 1&#44;155&#59; IC 95&#37; 1&#44;020-1&#44;307&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;023&#41; o enfermedad renal cr&#243;nica &#40;RR 1&#44;360&#59; IC 95&#37; 1&#44;210-1&#44;529&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; as&#237; como peor clase funcional &#40;clase funcional NYHA III-IV&#41; &#40;RR 1&#44;280&#59; IC 95&#37; 1&#44;139-1&#44;438&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En este an&#225;lisis el tratamiento con IECA &#40;RR 0&#44;839&#59; IC 95&#37; 0&#44;736-0&#44;956&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#44; ARA-II &#40;RR 0&#44;766&#59; IC 95&#37; 0&#44;668-0&#44;878&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; betabloqueantes &#40;RR 0&#44;822&#59; IC 95&#37; 0&#44;731-0&#44;925&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41; y metformina son factores protectores&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Los resultados del forest plot se presentan en la <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>&#46; Como puede observarse&#44; la metformina mantiene su efecto protector para la mortalidad en la mayor&#237;a de los subgrupos&#44; excepto para los grupos de iSGLT2&#44; sulfonilureas y antecedentes de hipertensi&#243;n arterial&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Los pacientes que reciben tratamiento con metformina presentan menor mortalidad al a&#241;o de seguimiento &#40;RR 0&#44;814&#59; IC 95&#37; 0&#44;712-0&#44;930&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41; de forma significativa&#44; independientemente del resto de las variables &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discusi&#243;n</span><p id="par0090" class="elsevierStylePara elsevierViewall">En primer lugar&#44; llama la atenci&#243;n que se prescribi&#243; metformina al alta s&#243;lo en un tercio de los pacientes con DM&#44; por debajo de lo esperable seg&#250;n las recomendaciones de las GPC&#46; Los pacientes de los registros EAHFE y RICA son atendidos en SUH o en planta de hospitalizaci&#243;n de medicina interna y tienen un perfil m&#225;s geri&#225;trico que la poblaci&#243;n incluida en los ensayos cl&#237;nicos aleatorizados &#40;ECA&#41;&#44; con mayor edad&#44; fragilidad y comorbilidades&#46; Esta diferencia de poblaci&#243;n es una posible explicaci&#243;n para la infraprescripci&#243;n en nuestro estudio&#46; Otros estudios poblacionales que tambi&#233;n han reportado un porcentaje importante de infrautilizaci&#243;n de f&#225;rmacos como la metformina&#44; los arGLP-1 y los iSGLT2<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">39</span></a> la atribuyen al importante porcentaje de pacientes con edad avanzada de la poblaci&#243;n espa&#241;ola&#44; cuyas particularidades pueden limitar el uso de algunos f&#225;rmacos&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Sin embargo&#44; la infrautilizaci&#243;n de metformina tambi&#233;n se podr&#237;a explicar por adherencia a las GPC o por miedo a los efectos adversos &#40;EA&#41;&#46; Este f&#225;rmaco est&#225; contraindicado cuando el filtrado glomerular es<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> y se recomienda suspenderlo en pacientes graves con riesgo de insuficiencia renal aguda o acidosis metab&#243;lica&#46; El temor al desarrollo de EA&#44; en particular de acidosis l&#225;ctica&#44; es la principal causa de la tendencia a retirar este f&#225;rmaco en los pacientes hospitalizados de forma sistem&#225;tica e independiente de la situaci&#243;n cl&#237;nica del paciente&#44; a pesar de que la evidencia cient&#237;fica a este respecto ha evolucionado en los &#250;ltimos a&#241;os&#46; En el pasado&#44; aunque algunos estudios ya evidenciaban que esta asociaci&#243;n pod&#237;a ser casual<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">40</span></a>&#44; el uso de metformina en pacientes con IC descompensada o avanzada &#40;NYHA III-IV&#41; no estaba recomendado en las GPC&#46; Posteriormente se ha demostrado en registros o estudios observacionales que el riesgo de esta complicaci&#243;n es independiente de la toma de metformina<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">41&#44;42</span></a>&#46; En la &#250;ltima GPC de DM<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">28</span></a> se establece que la metformina es segura en todas las fases de IC con funci&#243;n renal conservada o moderadamente reducida &#40;filtrado glomerular<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&#44; y tiene menor riesgo de mortalidad o ingreso por IC comparada con insulina y sulfonilureas&#46; En dicho documento tambi&#233;n se rechaza el riesgo de acidosis l&#225;ctica en relaci&#243;n con este f&#225;rmaco<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">41&#44;43&#44;44</span></a>&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Como hemos introducido previamente&#44; la metformina demostr&#243; reducir las complicaciones cardiovasculares en DM&#44; disminuyendo en un 30&#37; la mortalidad total y de causa cardiovascular&#44; en un 39&#37; el infarto agudo de miocardio y en un 41&#37; el accidente cerebrovascular en los primeros 10 a&#241;os del diagn&#243;stico<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">31</span></a>&#46; Sin embargo&#44; hasta ahora no se han desarrollado ECA para evaluar el efecto de la metformina a nivel cardiovascular&#46; Tras los estudios pivotales de los arGLP-1 y los iSGLT2&#44; estos f&#225;rmacos se sit&#250;an ya en las gu&#237;as de DM<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">28</span></a> como los f&#225;rmacos de elecci&#243;n en los pacientes con DM y muy alto riesgo cardiovascular&#44; recomend&#225;ndolos incluso de inicio en algunos casos&#46; No obstante&#44; cuando se realizaron estos ECA la mayor&#237;a recib&#237;a tratamiento concomitante con metformina y se evaluaron sus efectos sumados a los de este f&#225;rmaco&#46; El ECA DANish con el subestudio Met-HeFT est&#225; dise&#241;ado para evaluar la eficacia y seguridad de la metformina en pacientes con IC cr&#243;nica&#59; actualmente se encuentra en fase 4 y aportar&#225; por primera vez datos sobre el riesgo de acidosis l&#225;ctica en un ECA<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">45</span></a>&#46; En espera de su publicaci&#243;n&#44; la evidencia cient&#237;fica disponible en el momento actual ha permitido que tanto las GPC de IC<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">11</span></a> como de DM<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">28</span></a> recomienden el uso de la metformina en este perfil de pacientes&#46; Los resultados de nuestro estudio refuerzan esta recomendaci&#243;n&#44; ya que los pacientes con DM tipo 2 e IC en tratamiento con metformina presentaron menor mortalidad al a&#241;o de seguimiento&#44; independientemente del resto de los factores&#46; Por tanto&#44; consideramos que la prescripci&#243;n de este f&#225;rmaco en este grupo de pacientes debe continuar siendo un pilar fundamental en el tratamiento y evitar su infraprescripci&#243;n por miedo a potenciales EA&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">En segundo lugar&#44; hay que se&#241;alar que en nuestro estudio el porcentaje de pacientes en tratamiento con f&#225;rmacos del grupo arGLP-1 e iSGLT-2 es muy reducido&#44; debido a que la inclusi&#243;n de pacientes finaliz&#243; en 2018&#44; antes de la generalizaci&#243;n de su uso en este perfil de pacientes&#46; Aunque el grupo de pacientes con DM tipo 2 en tratamiento con metformina de nuestro estudio ten&#237;a un mayor porcentaje de asociaci&#243;n con iSGLT-2 que el grupo sin metformina&#44; estos suponen 40 del total de 1&#46;453 pacientes con DM en tratamiento con metformina&#44; por lo que no consideramos que nuestros resultados se hayan visto sesgados por la influencia de este grupo farmacol&#243;gico&#46; Consideramos que ser&#225; interesante realizar este an&#225;lisis de nuevo con las cohortes EAHFE y RICA posteriores a 2018&#44; en las que presumiblemente el porcentaje de pacientes tratados con estos grupos terap&#233;uticos ser&#225; mayor&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Este estudio tiene varias limitaciones&#46; En primer lugar&#44; al tratarse de un an&#225;lisis retrospectivo&#44; los resultados son correlaciones y no implican causalidad&#44; lo que nos permite &#250;nicamente formular hip&#243;tesis&#46; En segundo lugar&#44; puede existir un sesgo de selecci&#243;n al proceder los pacientes de centros adheridos voluntariamente y por ser el periodo de estudio muy amplio&#46; La tercera limitaci&#243;n est&#225; relacionada con la gran variabilidad&#44; tanto estructural como de gesti&#243;n&#44; de los centros participantes&#59; en este sentido&#44; es conocida la considerable heterogeneidad de las estrategias de control y seguimiento de la IC en Espa&#241;a<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">46&#44;47</span></a>&#46; En cuarto lugar&#44; el diagn&#243;stico de los pacientes se estableci&#243; por criterio cl&#237;nico&#44; y aunque en la mayor&#237;a de los casos se confirm&#243; con p&#233;ptidos natriur&#233;ticos o ecocardiograf&#237;a&#44; todav&#237;a existe la posibilidad de un error diagn&#243;stico&#46; En quinto lugar&#44; la asignaci&#243;n de los pacientes a los grupos con y sin tratamiento con metformina se hizo con base en la prescripci&#243;n en el momento del alta&#44; pero este aspecto no se monitoriz&#243; durante el seguimiento&#44; por lo que puede haber pacientes que hubiesen cambiado de grupo&#46; No obstante&#44; dada la experiencia que se tiene con este f&#225;rmaco&#44; creemos que el porcentaje de pacientes que pudieran haber cambiado de grupo ha sido bajo&#46; Sexta&#44; aunque en los modelos ajustados se tuvo en cuenta el grado de dependencia del paciente &#40;medido a trav&#233;s del &#237;ndice de Barthel&#41;&#44; no se ha tenido en cuenta la fragilidad&#44; y este es un aspecto con un importante impacto en los pacientes mayores y espec&#237;ficamente en los afectados de IC<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">48&#44;49</span></a>&#46; Por &#250;ltimo&#44; se trata de un an&#225;lisis en el cual no se ha realizado estimaci&#243;n del tama&#241;o muestral&#44; por lo que es posible que se haya incurrido en error estad&#237;stico de tipo beta en algunas de las estimaciones&#46; Sin embargo&#44; dado que nuestros resultados se basan en la informaci&#243;n obtenida de los 2 principales registros multic&#233;ntricos de pacientes con IC de Espa&#241;a&#44; consideramos que son representativos y potencialmente extrapolables al conjunto de la poblaci&#243;n espa&#241;ola&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Como conclusi&#243;n&#44; en nuestro estudio&#44; los pacientes con DM e IC que reciben tratamiento con metformina presentan menor mortalidad al a&#241;o de seguimiento&#46; Por tanto&#44; consideramos que la prescripci&#243;n de este f&#225;rmaco en este perfil de pacientes debe continuar siendo un pilar fundamental en el tratamiento y evitar su infraprescripci&#243;n por miedo a potenciales EA&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Financiaci&#243;n</span><p id="par0120" class="elsevierStylePara elsevierViewall">La presente investigaci&#243;n no ha recibido ayudas espec&#237;ficas provenientes de agencias del sector p&#250;blico&#44; sector comercial o entidades sin &#225;nimo de lucro&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicto de intereses</span><p id="par0125" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con diabetes mellitus &#40;DM&#41; e insuficiencia cardiaca &#40;IC&#41; presentan peor pron&#243;stico a pesar de los avances terap&#233;uticos en ambas enfermedades&#46; Los inhibidores del cotransportador sodio-glucosa tipo 2 y agonistas del receptor de GLP-1 han demostrado beneficios cardiovasculares y se han posicionado como primer escal&#243;n en el tratamiento de DM en pacientes con IC o elevado riesgo cardiovascular&#46; Sin embargo&#44; en los ensayos pivotales la mayor&#237;a de los pacientes recibe tratamiento concomitante con metformina&#46; Todav&#237;a no se han desarrollado ensayos cl&#237;nicos aleatorizados para evaluar el impacto pron&#243;stico de la metformina a nivel cardiovascular&#46; Nuestro objetivo fue analizar si los pacientes con DM e IC aguda que recib&#237;an tratamiento con metformina en el momento del alta podr&#237;an presentar mejor pron&#243;stico al a&#241;o de seguimiento&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ensayo de cohortes prospectivo mediante el an&#225;lisis combinado de los 2 principales registros espa&#241;oles de IC&#58; el Registro <span class="elsevierStyleItalic">Epidemiology of Acute Heart Failure in Emergency Departments</span> &#8211;EAHFE&#8211; y el Registro Nacional de Pacientes con Insuficiencia Cardiaca &#8211;RICA&#8211;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">De un total de 4&#46;403 pacientes con DM tipo 2&#44; recibi&#243; tratamiento con metformina el 33&#37; &#40;1&#46;453&#41;&#46; Este grupo present&#243; una mortalidad significativamente inferior al a&#241;o de tratamiento &#40;22 versus 32&#37;&#59; test de Log Rank p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En el an&#225;lisis ajustado de mortalidad&#44; los pacientes que recibieron tratamiento con metformina presentaron menor mortalidad al a&#241;o de seguimiento independientemente del resto de las variables &#40;RR 0&#44;814&#59; IC 95&#37; 0&#44;712-0&#44;930&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con DM tipo 2 e IC aguda que recibieron metformina presentaron mejor pron&#243;stico al a&#241;o de seguimiento&#44; por lo que consideramos que este f&#225;rmaco debe continuar siendo un pilar fundamental en el tratamiento de estos pacientes&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Patients with diabetes mellitus &#40;DM&#41; and heart failure &#40;HF&#41; have a worse prognosis despite therapeutic advances in both diseases&#46; Sodium-glucose co-transporter type 2 and GLP-1 receptor agonists have shown cardiovascular benefits and have been positioned as the first step in the treatment of DM in patients with HF or high cardiovascular risk&#46; However&#44; in the pivotal trials the majority of patients receives concomitant treatment with metformin&#46; Randomized clinical trials have not yet been developed to assess the prognostic impact of metformin at the cardiovascular level&#46; Our objective was to analyze whether patients with DM and acute HF who receive treatment with metformin at the time of discharge may have had a better prognosis at one year of follow-up&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Prospective cohort trial using the combined analysis of the 2 main Spanish HF registries&#58; the Epidemiology of Acute Heart Failure in Emergency Departments registry &#8211;EAHFE&#8211; and the National Registry of Patients with Heart Failure &#8211;RICA&#8211;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">33&#37; &#40;1453&#41; of a total of 4403 patients with DM type 2 received treatment with metformin&#46; This group presented significantly lower mortality after one year of treatment &#40;22 vs&#46; 32&#37;&#59; Log Rank test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In the adjusted analysis of mortality&#44; patients receiving treatment with metformin had lower mortality at one year of follow-up regardless of the rest of the variables &#40;RR 0&#46;814&#59; 95&#37; CI&#58; 0&#46;712&#8211;0&#46;930&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Patients with DM type 2 and acute HF who received metformin had a better prognosis after one year of follow-up&#44; so we believe that this drug should continue to be a fundamental pillar in the treatment of these patients&#46;</p></span>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">ACOD&#58; anticoagulante de acci&#243;n directa&#59; ADO&#58; antidiab&#233;ticos orales&#59; ARA-II&#58; antagonistas de los receptores de la angiotensina ii&#59; arGLP-1&#58; agonistas del receptor de GLP-1&#59; ARNI&#58; inhibidor de la neprilisina y del receptor de angiotensina&#59; DAI&#58; desfibrilador autom&#225;tico implantable&#59; DM&#58; diabetes mellitus&#59; EAHFE&#58; <span class="elsevierStyleItalic">Epidemiology of Acute Heart Failure in Emergency Departments&#59;</span> EPOC&#58; enfermedad pulmonar obstructiva cr&#243;nica&#59; FEVI&#58; fracci&#243;n de eyecci&#243;n de ventr&#237;culo izquierdo&#59; HTA&#58; hipertensi&#243;n arterial&#59; IDPP-4&#58; inhibidores de la dipeptidil peptidasa-4&#59; IECA&#58; inhibidores de la enzima convertidora de angiotensina&#59; iSGLT2&#58; inhibidores del cotransportador sodio-glucosa tipo 2&#59; NYHA&#58; <span class="elsevierStyleItalic">New York Heart Association&#59;</span> RICA&#58; Registro Nacional de Pacientes con Insuficiencia Cardiaca&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pacientes con DM tipo 2 en tratamiento con metformina</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col">Total de pacientes con DM tipo 2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">2&#46;710 &#40;91&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Dislipidemia</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;776 &#40;63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;825 &#40;61&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">951 &#40;65&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cardiopat&#237;a isqu&#233;mica</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;425 &#40;32&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;003 &#40;34&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">422 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Enfermedad renal cr&#243;nica</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;834 &#40;41&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;479 &#40;50&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">355 &#40;24&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Enfermedad cerebrovascular</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">614 &#40;13&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">408 &#40;13&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">206 &#40;14&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;755&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Fibrilaci&#243;n auricular</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;164 &#40;49&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;467 &#40;49&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">697 &#40;48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;272&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Arteriopat&#237;a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">594 &#40;13&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">417 &#40;14&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">177 &#40;12&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;076&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Valvulopat&#237;a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">350 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">221 &#40;14&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">129 &#40;15&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;514&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">EPOC</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;015 &#40;23&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">691 &#40;23&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">324 &#40;22&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;411&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Demenci</span>a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">288 &#40;6&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">205 &#40;6&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">83 &#40;5&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Neoplasia activa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">548 &#40;12&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">378 &#40;12&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">170 &#40;11&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;294&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cirrosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 &#40;1&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;1&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;055&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Estado basal</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Clase funcional medida con la escala NYHA</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Clase funcional NYHA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NYHA I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">579 &#40;13&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">346 &#40;11&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">233 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NYHA II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;355 &#40;53&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;557 &#40;52&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">798 &#40;54&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NYHA III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;382 &#40;31&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">991 &#40;33&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">391 &#40;26&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NYHA IV&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">87 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">56 &#40;1&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">31 &#40;2&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NYHA III-IV&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;469 &#40;33&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;047 &#40;35&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">422 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">FEVI</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>FEVI<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">51&#44;9 &#40;14&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#205;ndice de Barthel</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#205;ndice de Barthel<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&#44;29 &#40;22&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&#44;61 &#40;23&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&#44;84 &#40;0&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Tratamiento diur&#233;tico</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Diur&#233;ticos de asa</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#46;209 &#40;72&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;118 &#40;71&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;091 &#40;75&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;019</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">F&#225;rmacos modificadores de la enfermedad</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">IECA</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;447 &#40;32&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">871 &#40;29&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">576 &#40;39&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ARA-II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;175 &#40;26&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">721 &#40;24&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">454 &#40;31&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ARNI &#40;sacubitrilo-valsart&#225;n&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 &#40;1&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">42 &#40;1&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">26 &#40;1&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;353&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Betabloqueantes</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;666 &#40;60&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;674 &#40;56&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">992 &#40;68&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonistas del receptor de aldosterona</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">855 &#40;19&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">566 &#40;19&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">289 &#40;19&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;572&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Ivabradina</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72 &#40;1&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">49 &#40;1&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 &#40;1&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Otros f&#225;rmacos</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonistas del calcio</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;205 &#40;27&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">798 &#40;27&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">407 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#44;025 &#40;1&#44;018-1&#44;033&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;026 &#40;1&#44;018-1&#44;033&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dislipidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;949 &#40;0&#44;840-1&#44;073&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;404&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cardiopat&#237;a isqu&#233;mica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;172 &#40;1&#44;029-1&#44;334&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;017</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;155 &#40;1&#44;020-1&#44;307&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;023</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Enfermedad renal cr&#243;nica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;372 &#40;1&#44;219-1&#44;545&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;360 &#40;1&#44;210-1&#44;529&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Clase funcional NYHA III-IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;267 &#40;1&#44;127-1&#44;424&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;280 &#40;1&#44;139-1&#44;438&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#205;ndice de Barthel&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;988 &#40;0&#44;986-0&#44;990&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;988 &#40;0&#44;986-0&#44;990&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diur&#233;ticos de asa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;218 &#40;1&#44;066-1&#44;391&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;005</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;231 &#40;1&#44;081-1&#44;403&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;01</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IECA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;832 &#40;0&#44;729-0&#44;950&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;007</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;839 &#40;0&#44;736-0&#44;956&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;01</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ARA-II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;761 &#40;0&#44;662-0&#44;875&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;766 &#40;0&#44;668-0&#44;878&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Betabloqueantes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;824 &#40;0&#44;731-0&#44;929&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;002</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;822 &#40;0&#44;731-0&#44;925&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;01</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Digoxina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;146 &#40;0&#44;962-1&#44;365&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nitratos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;172 &#40;1&#44;017-1&#44;350&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;028</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;183 &#40;1&#44;030-1&#44;358&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;05</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hidralazina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;943 &#40;0&#44;633-1&#44;406&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;774&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Antiagregantes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;039 &#40;0&#44;913-1&#44;183&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;558&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anticoagulantes directos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;909 &#40;0&#44;753-1&#44;097&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;321&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Estatinas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;917 &#40;0&#44;807-1&#44;043&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;186&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ADO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;048 &#40;0&#44;918-1&#44;196&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;487&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Insulina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;066 &#40;0&#44;908-1&#44;251&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;443&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Sulfonilureas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;802 &#40;0&#44;634-1&#44;016&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">DPP4-i&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;036 &#40;0&#44;852-1&#44;260&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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          "es" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">An&#225;lisis univariante y multivariante an&#225;lisis de regresi&#243;n de Cox para mortalidad al a&#241;o</p>"
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                      "titulo" => "Global healthcare expenditure on diabetes for 2010 and 2030"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Zhang"
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                            2 => "J&#46; Brown"
                            3 => "D&#46; Vistisen"
                            4 => "R&#46; Sicree"
                            5 => "J&#46; Shaw"
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                    0 => array:2 [
                      "doi" => "10.1016/j.diabres.2010.01.026"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Insuficiencia cardiaca y diabetes&#58; la confrontaci&#243;n de dos grandes epidemias del siglo <span class="elsevierStyleSmallCaps">xxi</span>"
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                        0 => array:2 [
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                    0 => array:2 [
                      "doi" => "10.1016/j.rce.2019.01.009"
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                        "tituloSerie" => "Rev Clin Esp&#46;"
                        "fecha" => "2020"
                        "volumen" => "220"
                        "paginaInicial" => "135"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "National trends in heart failure hospitalization rates in patients with diabetes mellitus&#58; 1997-2010"
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                        0 => array:2 [
                          "etal" => false
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                    0 => array:2 [
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                        "tituloSerie" => "Rev Esp Cardiol&#46;"
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                      "titulo" => "Changes over time in the association between type 2 diabetes and post-discharge outcomes in decompensated chronic heart failure patients&#58; Findings from the RICA Registry"
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                      "Revista" => array:5 [
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                      "titulo" => "Mortality among patients hospitalized with heart failure and diabetes mellitus&#58; Results from the National Inpatient Sample 2000-2010"
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                      "titulo" => "Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure&#58; Findings from the EVEREST trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Sarma"
                            1 => "R&#46;J&#46; Mentz"
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                            3 => "A&#46;J&#46; Fought"
                            4 => "M&#46; Huffman"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Heart Fail&#46;"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Influence of diabetes on characteristics and outcomes in patients hospitalized with heart failure&#58; A report from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure &#40;OPTIMIZE-HF&#41;"
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                            5 => "R&#46; Clare"
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am Heart J&#46;"
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                        "paginaFinal" => "654"
                      ]
                    ]
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                      "titulo" => "Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure - An analysis of the Candesartan in Heart failure&#58; Assessment of Reduction in Mortality and morbidity &#40;CHARM&#41; programme"
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                        0 => array:2 [
                          "etal" => true
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ORIGINAL
Impacto pronóstico de metformina en pacientes con diabetes mellitus tipo 2 e insuficiencia cardiaca aguda. Análisis combinado de los registros EAHFE y RICA
Prognostic impact of metformin in patients with type 2 diabetes mellitus and acute heart failure: Combined analysis of the EAHFE and RICA registries
M. Povar-Echeverríaa,
Autor para correspondencia
mpovar@salud.aragon.es

Autor para correspondencia.
, M. Méndez-Bailónb,c,d, F.J. Martín-Sánchezc,d,e, M. Montero-Pérez-Barquerof,g, J.C. Trullàsh,i, Ò. Mirój,k
a Servicio de Medicina Interna, Hospital Comarcal de Barbastro, Barbastro, Huesca, España
b Servicio de Medicina Interna, Hospital Universitario Clínico San Carlos, Madrid, España
c Facultad de Medicina, Universidad Complutense, Madrid, España
d Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IDISS), Madrid, España
e Servicio de Urgencias, Hospital Universitario Clínico San Carlos, Madrid, España
f Servicio de Medicina Interna, Hospital Universitario Reina Sofía, Córdoba, España
g Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, España
h Servicio de Medicina Interna, Hospital d’Olot i Comarcal de la Garrotxa, Olot, Girona, España
i Grupo de Investigación en Reparación y Regeneración Tisular (TR2Lab), Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central, Barcelona, España
j Servicio de Urgencias, Hospital Clínic de Barcelona, Barcelona, España
k Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, España
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y 2 grupos de f&#225;rmacos hipoglucemiantes&#44; los inhibidores del cotransportador sodio-glucosa tipo 2 &#40;iSGLT2&#41; y los agonistas del receptor de GLP-1 &#40;arGLP-1&#41; han demostrado beneficios a nivel cardiovascular tanto en pacientes con DM tipo 2 como en los que no la presentan<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">12&#8211;27</span></a>&#46; La &#250;ltima gu&#237;a europea de DM<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">28</span></a> recomienda estos f&#225;rmacos como tratamiento de inicio en los pacientes de riesgo cardiovascular alto o muy alto y que no est&#233;n recibiendo todav&#237;a metformina&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">La metformina es un f&#225;rmaco cl&#225;sico dentro del tratamiento de la DM tipo 2<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">29&#44;30</span></a>&#46; Por su evidencia en el descenso en las complicaciones macrovasculares<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">31</span></a>&#44; las gu&#237;as lo recomiendan como primera opci&#243;n de tratamiento en la mayor&#237;a de los pacientes&#46; Sin embargo&#44; su efecto en el pron&#243;stico de los pacientes con IC todav&#237;a no ha sido investigado&#46; El objetivo principal de este estudio fue analizar si los pacientes con DM e IC aguda que reciben tratamiento con metformina en el momento del alta presentan mejor pron&#243;stico al a&#241;o de seguimiento&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Dise&#241;o y fuente de los datos</span><p id="par0020" class="elsevierStylePara elsevierViewall">Planteamos un estudio observacional de cohortes prospectivo en el que combinamos datos de pacientes incluidos en los 2 principales registros espa&#241;oles de IC&#58; el registro <span class="elsevierStyleItalic">Epidemiology of Acute Heart Failure in Emergency Departments</span> &#40;EAHFE&#41; y el RICA&#46; Se trata de un estudio de efectividad que pretende valorar en una poblaci&#243;n real el uso de la metformina y su impacto pron&#243;stico al a&#241;o de seguimiento&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">El registro EAHFE es un estudio de cohorte multic&#233;ntrico&#44; de car&#225;cter anal&#237;tico no intervencionista con seguimiento prospectivo<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">32&#8211;34</span></a>&#44; promovido por el Grupo de Trabajo de Insuficiencia Cardiaca de la Sociedad Espa&#241;ola de Medicina de Urgencias y Emergencias&#46; Participan un total de 45 servicios de urgencias hospitalarios &#40;SUH&#41; espa&#241;oles&#44; que han incorporado 18&#46;370 pacientes diagnosticados de IC aguda entre 2007 y 2018&#44; en 6 periodos de selecci&#243;n de 1-2 meses cada 2 o 3 a&#241;os&#46; Este registro no incluye ninguna intervenci&#243;n planificada ni modifica la atenci&#243;n recibida por el m&#233;dico asistencial&#44; la cual est&#225; basada en las gu&#237;as de pr&#225;ctica cl&#237;nica &#40;GPC&#41; y los protocolos de cada centro hospitalario&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">El RICA es un estudio de cohorte prospectivo multic&#233;ntrico<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">35&#44;36</span></a> del Grupo de Trabajo Insuficiencia Cardiaca y Fibrilaci&#243;n Auricular de la Sociedad Espa&#241;ola de Medicina Interna&#46; Participan 52 centros p&#250;blicos y privados de Espa&#241;a y est&#225; activo desde 2008&#46; En &#233;l se incluyen pacientes &#250;nicos consecutivos&#44; mayores de 50 a&#241;os&#44; con diagn&#243;stico de IC al alta hospitalaria tras un episodio de descompensaci&#243;n de IC de nueva aparici&#243;n&#44; de acuerdo con la definici&#243;n de las gu&#237;as de la Sociedad Europea de Cardiolog&#237;a vigentes<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">37</span></a>&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Poblaci&#243;n de estudio</span><p id="par0035" class="elsevierStylePara elsevierViewall">Se incluyeron todos los pacientes del RICA hasta el a&#241;o 2018 y las poblaciones de EAHFE-5 &#40;periodo de inclusi&#243;n del 1 de enero al 29 de febrero de 2016&#44; con participaci&#243;n de 30 SUH&#41; y EAHFE-6 &#40;periodo de inclusi&#243;n del 1 de febrero al 31 de marzo de 2018&#44; con participaci&#243;n de 34 SUH&#41;&#44; en las cuales se recogieron datos relacionados con el tratamiento de la DM&#46; Tras realizar los tr&#225;mites pertinentes en cuanto a permisos de manejo de datos para ambos registros&#44; se realiz&#243; una base de datos conjunta manteniendo todas las variables comunes y eliminando las no coincidentes&#44; para favorecer el an&#225;lisis unificado de ambas poblaciones de estudio&#46; Dentro de este grupo poblacional seleccionamos como poblaci&#243;n a estudio los pacientes con DM tipo 2 &#40;si constaba como diagn&#243;stico previo&#44; tomaban f&#225;rmacos hipoglucemiantes o si su concentraci&#243;n de hemoglobina glucosilada al ingreso era<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>6&#44;5&#37;&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Variables</span><p id="par0040" class="elsevierStylePara elsevierViewall">Se recogieron variables cl&#237;nicas y de tratamiento que han sido definidas en otros art&#237;culos previos del RICA<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">4</span></a> y el EAHFE<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">38</span></a>&#46; Se realiz&#243; un seguimiento a 12 meses desde el alta hospitalaria del episodio &#237;ndice de IC aguda&#44; y se registr&#243; la mortalidad al a&#241;o por cualquier causa mediante consulta de la historia cl&#237;nica o contacto directo&#44; y en caso necesario se verific&#243; en el registro de la Seguridad Social&#44; donde los pacientes fallecidos constan baja al d&#237;a siguiente del deceso&#46; Se excluyeron del estudio los pacientes que fallecieron en el hospital durante el episodio &#237;ndice&#46; Para calcular la variable de tiempo de seguimiento&#44; se dispone de la fecha de finalizaci&#243;n del estudio &#40;correspondiente al a&#241;o de seguimiento desde el episodio &#237;ndice&#41;&#44; la fecha de exitus o la fecha de p&#233;rdida de seguimiento en aquellos casos en que ocurri&#243; la p&#233;rdida de seguimiento antes del a&#241;o &#40;fecha de censura para el estudio de supervivencia&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Consideraciones &#233;ticas</span><p id="par0045" class="elsevierStylePara elsevierViewall">El protocolo del RICA fue aprobado por el Comit&#233; de &#201;tica del Hospital Universitario Reina Sof&#237;a de C&#243;rdoba &#40;Espa&#241;a&#41; y el del registro EAHFE por el del Hospital Universitario Central de Asturias &#40;Oviedo&#44; Espa&#241;a&#41;&#46; Los n&#250;meros de referencia para las fases 5 y 6 son 160&#47;15 y 205&#47;17&#44; respectivamente&#46; Los datos fueron introducidos en bases de datos anonimizadas y han sido manejados de acuerdo con el RD 1720&#47;2007 que desarrolla la Ley Org&#225;nica 15&#47;1999&#44; de 13 de diciembre&#44; de Protecci&#243;n de Datos de Car&#225;cter Personal<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">4&#44;35&#44;36</span></a>&#46; El estudio se llev&#243; a cabo en estricto cumplimiento de los principios &#233;ticos de la Declaraci&#243;n de Helsinki&#46; Al tratarse de estudios observacionales de cohortes&#44; ambos registros siguieron las pautas STROBE para este m&#233;todo&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">An&#225;lisis estad&#237;stico</span><p id="par0050" class="elsevierStylePara elsevierViewall">Las variables cualitativas han sido expresadas como frecuencia y porcentaje&#46; Las variables cuantitativas continuas se muestran como media y desviaci&#243;n est&#225;ndar tras realizar la prueba de an&#225;lisis de normalidad de Kolmogorov-Smirnov&#46; El an&#225;lisis comparativo bivariante se realiz&#243; mediante la prueba de ji cuadrado cuando eran 2 pruebas cat&#233;goricas&#44; y mediante ANOVA para la comparaci&#243;n de variables cuantitativas de m&#225;s de 2 grupos&#46; Para el an&#225;lisis de mortalidad se realizaron las curvas de supervivencia de Kaplan-Meier y el test de Log Rank&#46; Se ha llevado a cabo un an&#225;lisis multivariante de riesgos proporcionales de regresi&#243;n de Cox por el m&#233;todo hacia atr&#225;s condicional para las variables que en el an&#225;lisis univariante mostraban una relaci&#243;n significativamente estad&#237;stica con la probabilidad de muerte&#46; El riesgo asociado a fallecer por cualquier causa en los pacientes en tratamiento se expres&#243; como riesgo relativo &#40;RR&#41; con su intervalo de confianza del 95&#37; &#40;IC 95&#37;&#41; respecto a los pacientes que no recib&#237;an metformina&#46; Se ha realizado un <span class="elsevierStyleItalic">forest plot</span> para valorar c&#243;mo se comporta la metformina en diferentes subpoblaciones de pacientes&#46; Todos los an&#225;lisis estad&#237;sticos se realizaron con SPSS&#174; 26&#46;0 &#40;IBM&#44; Chicago&#44; IL&#44; EE&#46; UU&#46;&#41;&#46; La significaci&#243;n estad&#237;stica se estableci&#243; como p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 o si el IC 95&#37; de la <span class="elsevierStyleItalic">hazard ratio</span> no inclu&#237;a el valor 1&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Resultados</span><p id="par0055" class="elsevierStylePara elsevierViewall">Del total de 10&#46;122 pacientes incluidos al aunar las bases de datos EAHFE y RICA&#44; se incluyeron 4&#46;403 pacientes con DM tipo 2&#44; lo que supone el 43&#44;5&#37; del total&#46; El an&#225;lisis de subgrupos se realiz&#243; en funci&#243;n de si recib&#237;an o no tratamiento con metformina al alta del episodio &#237;ndice de descompensaci&#243;n &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se describen las caracter&#237;sticas del grupo de pacientes con DM tipo 2 y de ambos subgrupos&#46; Los 1&#46;453 pacientes que reciben tratamiento con metformina tras el alta hospitalaria representan un 33&#37; del total de los pacientes con DM tipo 2&#46; Estos pacientes son m&#225;s j&#243;venes &#40;77 versus 79 a&#241;os&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y presentan menor comorbilidad&#44; siendo significativamente inferior la prevalencia de cardiopat&#237;a isqu&#233;mica &#40;29 versus 34&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;011&#41; y enfermedad renal cr&#243;nica &#40;24 versus 50&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; Adem&#225;s&#44; presentan mejor situaci&#243;n funcional&#44; con menor porcentaje de clase funcional NYHA III-IV &#40;35 versus 29&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y mayor puntuaci&#243;n en el &#237;ndice de Barthel &#40;84 versus 79&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; Los f&#225;rmacos que reciben ambos grupos respecto al tratamiento de IC est&#225;n expuestos en la tabla y respecto al tratamiento de DM&#44; el grupo de metformina presenta con mayor frecuencia otros antidiab&#233;ticos orales asociados y menor porcentaje de insulinizaci&#243;n &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">En el seguimiento a 12 meses &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#44; se observa que el grupo de pacientes con metformina al alta presenta una mortalidad significativamente inferior &#40;22 versus 32&#37;&#59; test de Log Rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Se realiza an&#225;lisis univariante y multivariante respecto a la mortalidad al a&#241;o de seguimiento &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; En el an&#225;lisis ajustado&#44; los pacientes que presentan mayor mortalidad al a&#241;o de seguimiento tienen mayor edad &#40;RR 1&#44;025&#59; IC 95&#37; 1&#44;018-1&#44;033&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y presentan con mayor frecuencia comorbilidad asociada&#44; como cardiopat&#237;a isqu&#233;mica &#40;RR 1&#44;155&#59; IC 95&#37; 1&#44;020-1&#44;307&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;023&#41; o enfermedad renal cr&#243;nica &#40;RR 1&#44;360&#59; IC 95&#37; 1&#44;210-1&#44;529&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; as&#237; como peor clase funcional &#40;clase funcional NYHA III-IV&#41; &#40;RR 1&#44;280&#59; IC 95&#37; 1&#44;139-1&#44;438&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En este an&#225;lisis el tratamiento con IECA &#40;RR 0&#44;839&#59; IC 95&#37; 0&#44;736-0&#44;956&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#44; ARA-II &#40;RR 0&#44;766&#59; IC 95&#37; 0&#44;668-0&#44;878&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; betabloqueantes &#40;RR 0&#44;822&#59; IC 95&#37; 0&#44;731-0&#44;925&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41; y metformina son factores protectores&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Los resultados del forest plot se presentan en la <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>&#46; Como puede observarse&#44; la metformina mantiene su efecto protector para la mortalidad en la mayor&#237;a de los subgrupos&#44; excepto para los grupos de iSGLT2&#44; sulfonilureas y antecedentes de hipertensi&#243;n arterial&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Los pacientes que reciben tratamiento con metformina presentan menor mortalidad al a&#241;o de seguimiento &#40;RR 0&#44;814&#59; IC 95&#37; 0&#44;712-0&#44;930&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41; de forma significativa&#44; independientemente del resto de las variables &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discusi&#243;n</span><p id="par0090" class="elsevierStylePara elsevierViewall">En primer lugar&#44; llama la atenci&#243;n que se prescribi&#243; metformina al alta s&#243;lo en un tercio de los pacientes con DM&#44; por debajo de lo esperable seg&#250;n las recomendaciones de las GPC&#46; Los pacientes de los registros EAHFE y RICA son atendidos en SUH o en planta de hospitalizaci&#243;n de medicina interna y tienen un perfil m&#225;s geri&#225;trico que la poblaci&#243;n incluida en los ensayos cl&#237;nicos aleatorizados &#40;ECA&#41;&#44; con mayor edad&#44; fragilidad y comorbilidades&#46; Esta diferencia de poblaci&#243;n es una posible explicaci&#243;n para la infraprescripci&#243;n en nuestro estudio&#46; Otros estudios poblacionales que tambi&#233;n han reportado un porcentaje importante de infrautilizaci&#243;n de f&#225;rmacos como la metformina&#44; los arGLP-1 y los iSGLT2<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">39</span></a> la atribuyen al importante porcentaje de pacientes con edad avanzada de la poblaci&#243;n espa&#241;ola&#44; cuyas particularidades pueden limitar el uso de algunos f&#225;rmacos&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Sin embargo&#44; la infrautilizaci&#243;n de metformina tambi&#233;n se podr&#237;a explicar por adherencia a las GPC o por miedo a los efectos adversos &#40;EA&#41;&#46; Este f&#225;rmaco est&#225; contraindicado cuando el filtrado glomerular es<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> y se recomienda suspenderlo en pacientes graves con riesgo de insuficiencia renal aguda o acidosis metab&#243;lica&#46; El temor al desarrollo de EA&#44; en particular de acidosis l&#225;ctica&#44; es la principal causa de la tendencia a retirar este f&#225;rmaco en los pacientes hospitalizados de forma sistem&#225;tica e independiente de la situaci&#243;n cl&#237;nica del paciente&#44; a pesar de que la evidencia cient&#237;fica a este respecto ha evolucionado en los &#250;ltimos a&#241;os&#46; En el pasado&#44; aunque algunos estudios ya evidenciaban que esta asociaci&#243;n pod&#237;a ser casual<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">40</span></a>&#44; el uso de metformina en pacientes con IC descompensada o avanzada &#40;NYHA III-IV&#41; no estaba recomendado en las GPC&#46; Posteriormente se ha demostrado en registros o estudios observacionales que el riesgo de esta complicaci&#243;n es independiente de la toma de metformina<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">41&#44;42</span></a>&#46; En la &#250;ltima GPC de DM<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">28</span></a> se establece que la metformina es segura en todas las fases de IC con funci&#243;n renal conservada o moderadamente reducida &#40;filtrado glomerular<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&#44; y tiene menor riesgo de mortalidad o ingreso por IC comparada con insulina y sulfonilureas&#46; En dicho documento tambi&#233;n se rechaza el riesgo de acidosis l&#225;ctica en relaci&#243;n con este f&#225;rmaco<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">41&#44;43&#44;44</span></a>&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Como hemos introducido previamente&#44; la metformina demostr&#243; reducir las complicaciones cardiovasculares en DM&#44; disminuyendo en un 30&#37; la mortalidad total y de causa cardiovascular&#44; en un 39&#37; el infarto agudo de miocardio y en un 41&#37; el accidente cerebrovascular en los primeros 10 a&#241;os del diagn&#243;stico<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">31</span></a>&#46; Sin embargo&#44; hasta ahora no se han desarrollado ECA para evaluar el efecto de la metformina a nivel cardiovascular&#46; Tras los estudios pivotales de los arGLP-1 y los iSGLT2&#44; estos f&#225;rmacos se sit&#250;an ya en las gu&#237;as de DM<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">28</span></a> como los f&#225;rmacos de elecci&#243;n en los pacientes con DM y muy alto riesgo cardiovascular&#44; recomend&#225;ndolos incluso de inicio en algunos casos&#46; No obstante&#44; cuando se realizaron estos ECA la mayor&#237;a recib&#237;a tratamiento concomitante con metformina y se evaluaron sus efectos sumados a los de este f&#225;rmaco&#46; El ECA DANish con el subestudio Met-HeFT est&#225; dise&#241;ado para evaluar la eficacia y seguridad de la metformina en pacientes con IC cr&#243;nica&#59; actualmente se encuentra en fase 4 y aportar&#225; por primera vez datos sobre el riesgo de acidosis l&#225;ctica en un ECA<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">45</span></a>&#46; En espera de su publicaci&#243;n&#44; la evidencia cient&#237;fica disponible en el momento actual ha permitido que tanto las GPC de IC<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">11</span></a> como de DM<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">28</span></a> recomienden el uso de la metformina en este perfil de pacientes&#46; Los resultados de nuestro estudio refuerzan esta recomendaci&#243;n&#44; ya que los pacientes con DM tipo 2 e IC en tratamiento con metformina presentaron menor mortalidad al a&#241;o de seguimiento&#44; independientemente del resto de los factores&#46; Por tanto&#44; consideramos que la prescripci&#243;n de este f&#225;rmaco en este grupo de pacientes debe continuar siendo un pilar fundamental en el tratamiento y evitar su infraprescripci&#243;n por miedo a potenciales EA&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">En segundo lugar&#44; hay que se&#241;alar que en nuestro estudio el porcentaje de pacientes en tratamiento con f&#225;rmacos del grupo arGLP-1 e iSGLT-2 es muy reducido&#44; debido a que la inclusi&#243;n de pacientes finaliz&#243; en 2018&#44; antes de la generalizaci&#243;n de su uso en este perfil de pacientes&#46; Aunque el grupo de pacientes con DM tipo 2 en tratamiento con metformina de nuestro estudio ten&#237;a un mayor porcentaje de asociaci&#243;n con iSGLT-2 que el grupo sin metformina&#44; estos suponen 40 del total de 1&#46;453 pacientes con DM en tratamiento con metformina&#44; por lo que no consideramos que nuestros resultados se hayan visto sesgados por la influencia de este grupo farmacol&#243;gico&#46; Consideramos que ser&#225; interesante realizar este an&#225;lisis de nuevo con las cohortes EAHFE y RICA posteriores a 2018&#44; en las que presumiblemente el porcentaje de pacientes tratados con estos grupos terap&#233;uticos ser&#225; mayor&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Este estudio tiene varias limitaciones&#46; En primer lugar&#44; al tratarse de un an&#225;lisis retrospectivo&#44; los resultados son correlaciones y no implican causalidad&#44; lo que nos permite &#250;nicamente formular hip&#243;tesis&#46; En segundo lugar&#44; puede existir un sesgo de selecci&#243;n al proceder los pacientes de centros adheridos voluntariamente y por ser el periodo de estudio muy amplio&#46; La tercera limitaci&#243;n est&#225; relacionada con la gran variabilidad&#44; tanto estructural como de gesti&#243;n&#44; de los centros participantes&#59; en este sentido&#44; es conocida la considerable heterogeneidad de las estrategias de control y seguimiento de la IC en Espa&#241;a<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">46&#44;47</span></a>&#46; En cuarto lugar&#44; el diagn&#243;stico de los pacientes se estableci&#243; por criterio cl&#237;nico&#44; y aunque en la mayor&#237;a de los casos se confirm&#243; con p&#233;ptidos natriur&#233;ticos o ecocardiograf&#237;a&#44; todav&#237;a existe la posibilidad de un error diagn&#243;stico&#46; En quinto lugar&#44; la asignaci&#243;n de los pacientes a los grupos con y sin tratamiento con metformina se hizo con base en la prescripci&#243;n en el momento del alta&#44; pero este aspecto no se monitoriz&#243; durante el seguimiento&#44; por lo que puede haber pacientes que hubiesen cambiado de grupo&#46; No obstante&#44; dada la experiencia que se tiene con este f&#225;rmaco&#44; creemos que el porcentaje de pacientes que pudieran haber cambiado de grupo ha sido bajo&#46; Sexta&#44; aunque en los modelos ajustados se tuvo en cuenta el grado de dependencia del paciente &#40;medido a trav&#233;s del &#237;ndice de Barthel&#41;&#44; no se ha tenido en cuenta la fragilidad&#44; y este es un aspecto con un importante impacto en los pacientes mayores y espec&#237;ficamente en los afectados de IC<a class="elsevierStyleCrossRefs" href="#bib0485"><span class="elsevierStyleSup">48&#44;49</span></a>&#46; Por &#250;ltimo&#44; se trata de un an&#225;lisis en el cual no se ha realizado estimaci&#243;n del tama&#241;o muestral&#44; por lo que es posible que se haya incurrido en error estad&#237;stico de tipo beta en algunas de las estimaciones&#46; Sin embargo&#44; dado que nuestros resultados se basan en la informaci&#243;n obtenida de los 2 principales registros multic&#233;ntricos de pacientes con IC de Espa&#241;a&#44; consideramos que son representativos y potencialmente extrapolables al conjunto de la poblaci&#243;n espa&#241;ola&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Como conclusi&#243;n&#44; en nuestro estudio&#44; los pacientes con DM e IC que reciben tratamiento con metformina presentan menor mortalidad al a&#241;o de seguimiento&#46; Por tanto&#44; consideramos que la prescripci&#243;n de este f&#225;rmaco en este perfil de pacientes debe continuar siendo un pilar fundamental en el tratamiento y evitar su infraprescripci&#243;n por miedo a potenciales EA&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Financiaci&#243;n</span><p id="par0120" class="elsevierStylePara elsevierViewall">La presente investigaci&#243;n no ha recibido ayudas espec&#237;ficas provenientes de agencias del sector p&#250;blico&#44; sector comercial o entidades sin &#225;nimo de lucro&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicto de intereses</span><p id="par0125" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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    "fechaAceptado" => "2023-07-29"
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          "clase" => "keyword"
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          "identificador" => "xpalclavsec1737864"
          "palabras" => array:5 [
            0 => "Insuficiencia cardiaca"
            1 => "Diabetes mellitus"
            2 => "Metformina"
            3 => "Pron&#243;stico"
            4 => "Registro"
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        0 => array:4 [
          "clase" => "keyword"
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          "identificador" => "xpalclavsec1737863"
          "palabras" => array:5 [
            0 => "Heart failure"
            1 => "Diabetes mellitus"
            2 => "Metformin"
            3 => "Prognostic"
            4 => "Registry"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con diabetes mellitus &#40;DM&#41; e insuficiencia cardiaca &#40;IC&#41; presentan peor pron&#243;stico a pesar de los avances terap&#233;uticos en ambas enfermedades&#46; Los inhibidores del cotransportador sodio-glucosa tipo 2 y agonistas del receptor de GLP-1 han demostrado beneficios cardiovasculares y se han posicionado como primer escal&#243;n en el tratamiento de DM en pacientes con IC o elevado riesgo cardiovascular&#46; Sin embargo&#44; en los ensayos pivotales la mayor&#237;a de los pacientes recibe tratamiento concomitante con metformina&#46; Todav&#237;a no se han desarrollado ensayos cl&#237;nicos aleatorizados para evaluar el impacto pron&#243;stico de la metformina a nivel cardiovascular&#46; Nuestro objetivo fue analizar si los pacientes con DM e IC aguda que recib&#237;an tratamiento con metformina en el momento del alta podr&#237;an presentar mejor pron&#243;stico al a&#241;o de seguimiento&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ensayo de cohortes prospectivo mediante el an&#225;lisis combinado de los 2 principales registros espa&#241;oles de IC&#58; el Registro <span class="elsevierStyleItalic">Epidemiology of Acute Heart Failure in Emergency Departments</span> &#8211;EAHFE&#8211; y el Registro Nacional de Pacientes con Insuficiencia Cardiaca &#8211;RICA&#8211;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">De un total de 4&#46;403 pacientes con DM tipo 2&#44; recibi&#243; tratamiento con metformina el 33&#37; &#40;1&#46;453&#41;&#46; Este grupo present&#243; una mortalidad significativamente inferior al a&#241;o de tratamiento &#40;22 versus 32&#37;&#59; test de Log Rank p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En el an&#225;lisis ajustado de mortalidad&#44; los pacientes que recibieron tratamiento con metformina presentaron menor mortalidad al a&#241;o de seguimiento independientemente del resto de las variables &#40;RR 0&#44;814&#59; IC 95&#37; 0&#44;712-0&#44;930&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con DM tipo 2 e IC aguda que recibieron metformina presentaron mejor pron&#243;stico al a&#241;o de seguimiento&#44; por lo que consideramos que este f&#225;rmaco debe continuar siendo un pilar fundamental en el tratamiento de estos pacientes&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introducci&#243;n"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "M&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Resultados"
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            "identificador" => "abst0020"
            "titulo" => "Conclusiones"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Patients with diabetes mellitus &#40;DM&#41; and heart failure &#40;HF&#41; have a worse prognosis despite therapeutic advances in both diseases&#46; Sodium-glucose co-transporter type 2 and GLP-1 receptor agonists have shown cardiovascular benefits and have been positioned as the first step in the treatment of DM in patients with HF or high cardiovascular risk&#46; However&#44; in the pivotal trials the majority of patients receives concomitant treatment with metformin&#46; Randomized clinical trials have not yet been developed to assess the prognostic impact of metformin at the cardiovascular level&#46; Our objective was to analyze whether patients with DM and acute HF who receive treatment with metformin at the time of discharge may have had a better prognosis at one year of follow-up&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Prospective cohort trial using the combined analysis of the 2 main Spanish HF registries&#58; the Epidemiology of Acute Heart Failure in Emergency Departments registry &#8211;EAHFE&#8211; and the National Registry of Patients with Heart Failure &#8211;RICA&#8211;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">33&#37; &#40;1453&#41; of a total of 4403 patients with DM type 2 received treatment with metformin&#46; This group presented significantly lower mortality after one year of treatment &#40;22 vs&#46; 32&#37;&#59; Log Rank test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In the adjusted analysis of mortality&#44; patients receiving treatment with metformin had lower mortality at one year of follow-up regardless of the rest of the variables &#40;RR 0&#46;814&#59; 95&#37; CI&#58; 0&#46;712&#8211;0&#46;930&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Patients with DM type 2 and acute HF who received metformin had a better prognosis after one year of follow-up&#44; so we believe that this drug should continue to be a fundamental pillar in the treatment of these patients&#46;</p></span>"
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            "identificador" => "abst0030"
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            "identificador" => "abst0035"
            "titulo" => "Results"
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            "identificador" => "abst0040"
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Diagrama de flujo de los pacientes&#46; DM&#58; diabetes mellitus&#59; EAHFE&#58; <span class="elsevierStyleItalic">Epidemiology of Acute Heart Failure in Emergency Departments</span>&#59; RICA&#58; Registro Nacional de Pacientes con Insuficiencia Cardiaca&#46;</p>"
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          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Relaci&#243;n de metformina en diferentes subpoblaciones de pacientes&#46; IC 95&#37;&#58; intervalo de confianza del 95&#37;&#59; RR&#58; riesgo relativo&#46;</p>"
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        "identificador" => "fig0015"
        "etiqueta" => "Figura 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Diferencias en mortalidad al a&#241;o por cualquier causa en los pacientes con diabetes mellitus tipo 2 e insuficiencia cardiaca que reciben prescripci&#243;n de metformina al alta&#44; frente a los que no reciben tratamiento con este f&#225;rmaco&#46;</p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">ACOD&#58; anticoagulante de acci&#243;n directa&#59; ADO&#58; antidiab&#233;ticos orales&#59; ARA-II&#58; antagonistas de los receptores de la angiotensina ii&#59; arGLP-1&#58; agonistas del receptor de GLP-1&#59; ARNI&#58; inhibidor de la neprilisina y del receptor de angiotensina&#59; DAI&#58; desfibrilador autom&#225;tico implantable&#59; DM&#58; diabetes mellitus&#59; EAHFE&#58; <span class="elsevierStyleItalic">Epidemiology of Acute Heart Failure in Emergency Departments&#59;</span> EPOC&#58; enfermedad pulmonar obstructiva cr&#243;nica&#59; FEVI&#58; fracci&#243;n de eyecci&#243;n de ventr&#237;culo izquierdo&#59; HTA&#58; hipertensi&#243;n arterial&#59; IDPP-4&#58; inhibidores de la dipeptidil peptidasa-4&#59; IECA&#58; inhibidores de la enzima convertidora de angiotensina&#59; iSGLT2&#58; inhibidores del cotransportador sodio-glucosa tipo 2&#59; NYHA&#58; <span class="elsevierStyleItalic">New York Heart Association&#59;</span> RICA&#58; Registro Nacional de Pacientes con Insuficiencia Cardiaca&#46;</p>"
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Pacientes con DM tipo 2 en tratamiento con metformina</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Total de pacientes con DM tipo 2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">No&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col">S&#237;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;384 &#40;54&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;542 &#40;64&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">77&#44;85 &#40;9&#44;17&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sexo var&#243;n</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;087 &#40;47&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;395 &#40;47&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">692 &#40;47&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;825</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sexo femenino</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2&#46;314 &#40;52&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">760 &#40;52&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Comorbilidades</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">HTA</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#46;034 &#40;91&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#46;710 &#40;91&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;324 &#40;91&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;403&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Dislipidemia</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#46;776 &#40;63&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;825 &#40;61&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">951 &#40;65&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;02&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cardiopat&#237;a isqu&#233;mica</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#46;425 &#40;32&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;003 &#40;34&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">422 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Enfermedad renal cr&#243;nica</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#46;834 &#40;41&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;479 &#40;50&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">355 &#40;24&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Enfermedad cerebrovascular</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">614 &#40;13&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">408 &#40;13&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">206 &#40;14&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;755&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Fibrilaci&#243;n auricular</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2&#46;164 &#40;49&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;467 &#40;49&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">697 &#40;48&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;272&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Arteriopat&#237;a</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">594 &#40;13&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">417 &#40;14&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">177 &#40;12&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;076&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Valvulopat&#237;a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">350 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">221 &#40;14&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">129 &#40;15&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;514&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">EPOC</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;015 &#40;23&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">691 &#40;23&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">324 &#40;22&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">0&#44;411&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Demenci</span>a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">288 &#40;6&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">205 &#40;6&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">83 &#40;5&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">0&#44;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Neoplasia activa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">548 &#40;12&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">378 &#40;12&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">170 &#40;11&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;294&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cirrosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 &#40;1&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">17 &#40;1&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;055&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Estado basal</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Clase funcional medida con la escala NYHA</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Clase funcional NYHA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NYHA I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">579 &#40;13&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">346 &#40;11&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">233 &#40;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NYHA II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;355 &#40;53&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;557 &#40;52&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">798 &#40;54&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NYHA III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;382 &#40;31&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">991 &#40;33&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">391 &#40;26&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NYHA IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">87 &#40;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">56 &#40;1&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;2&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>NYHA III-IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;469 &#40;33&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;047 &#40;35&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">422 &#40;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">FEVI</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>FEVI<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#44;9 &#40;14&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#205;ndice de Barthel</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#205;ndice de Barthel<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&#44;29 &#40;22&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79&#44;61 &#40;23&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&#44;84 &#40;0&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Tratamiento diur&#233;tico</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Diur&#233;ticos de asa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;209 &#40;72&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;118 &#40;71&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;091 &#40;75&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;019</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">F&#225;rmacos modificadores de la enfermedad</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">IECA</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;447 &#40;32&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">871 &#40;29&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">576 &#40;39&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ARA-II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;175 &#40;26&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">721 &#40;24&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">454 &#40;31&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ARNI &#40;sacubitrilo-valsart&#225;n&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">68 &#40;1&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonistas del receptor de aldosterona</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">566 &#40;19&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">72 &#40;1&#44;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">Otros f&#225;rmacos</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonistas del calcio</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Digoxina</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Amiodarona</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Nitratos</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">833 &#40;18&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">246 &#40;16&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Hidralazina</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">79 &#40;1&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">68 &#40;2&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11 &#40;0&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antiagregantes</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;431 &#40;32&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">912 &#40;30&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">519 &#40;35&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Dicumar&#237;nicos</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;218 &#40;27&#44;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">792 &#40;26&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">425 &#40;29&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ACOD</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">506 &#40;11&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">318 &#40;10&#44;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">188 &#40;12&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Estatinas</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mortalidad</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;280 &#40;1&#44;139-1&#44;438&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;01</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">IECA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;832 &#40;0&#44;729-0&#44;950&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;007</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;839 &#40;0&#44;736-0&#44;956&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;01</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ARA-II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;761 &#40;0&#44;662-0&#44;875&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;766 &#40;0&#44;668-0&#44;878&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Betabloqueantes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;824 &#40;0&#44;731-0&#44;929&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;002</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;822 &#40;0&#44;731-0&#44;925&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;01</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Digoxina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;146 &#40;0&#44;962-1&#44;365&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nitratos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;172 &#40;1&#44;017-1&#44;350&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;183 &#40;1&#44;030-1&#44;358&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;05</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hidralazina&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;943 &#40;0&#44;633-1&#44;406&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;774&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Antiagregantes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Anticoagulantes directos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estatinas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Insulina&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;066 &#40;0&#44;908-1&#44;251&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Sulfonilureas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;802 &#40;0&#44;634-1&#44;016&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DPP4-i&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;036 &#40;0&#44;852-1&#44;260&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;724&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">iSGLT2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;718 &#40;0&#44;384-1&#44;333&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3371027.png"
              ]
            ]
          ]
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Información del artículo
ISSN: 00142565
Idioma original: Español
DOI:10.1016/j.rce.2023.07.007
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