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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Situaci&#243;n actual de la insuficiencia card&#237;aca&#46; Necesidades no cubiertas</span><p id="par0005" class="elsevierStylePara elsevierViewall">La insuficiencia card&#237;aca &#40;IC&#41; es una entidad frecuente&#44; con una prevalencia estimada en los pa&#237;ses desarrollados en torno al 2&#37; de la poblaci&#243;n adulta&#44; si bien se espera que aumente en los pr&#243;ximos a&#241;os&#44; principalmente por el envejecimiento de la poblaci&#243;n<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">1&#8211;5</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">La IC se asocia con una elevada morbimortalidad<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">6&#8211;9</span></a>&#46; Adem&#225;s&#44; la hospitalizaci&#243;n por IC es un factor predictor de mortalidad<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">1&#44;10</span></a>&#46; Igualmente&#44; la IC tiene un marcado impacto negativo sobre la calidad de vida de los pacientes<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">11</span></a>&#46; Asimismo&#44; los costes asociados a la IC son muy elevados&#44; siendo la hospitalizaci&#243;n el principal componente<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">12&#44;13</span></a>&#46; Afortunadamente&#44; la optimizaci&#243;n del tratamiento se asocia con una reducci&#243;n del coste sanitario<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">La IC con fracci&#243;n de eyecci&#243;n reducida &#40;IC-FEr&#41; es una enfermedad progresiva&#44; con un deterioro gradual de la funci&#243;n card&#237;aca a lo largo del tiempo&#44; en el que se intercalan per&#237;odos de descompensaci&#243;n aguda&#44; que empeoran a&#250;n m&#225;s el pron&#243;stico del paciente<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">15&#44;16</span></a>&#46; Aproximadamente uno de cada 6 pacientes con IC-FEr desarrollar&#225;n un empeoramiento en los siguientes 18 meses tras el diagn&#243;stico de IC<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">16</span></a>&#46; Asimismo&#44; el empeoramiento cr&#243;nico de la IC supone el 80&#37; de las hospitalizaciones por IC<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">17</span></a>&#46; Adem&#225;s de empeorar el pron&#243;stico&#44; cada vez que el paciente presenta un ingreso hospitalario&#44; estos suelen ser cada vez m&#225;s graves y prolongados&#44; y el tiempo entre las descompensaciones menor<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">18&#44;19</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">En consecuencia&#44; es necesario optimizar el tratamiento para tratar de disminuir la carga de enfermedad que supone la IC<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">16&#44;20&#8211;22</span></a>&#46; Pero&#44; para ello&#44; es imprescindible comprender que la etiopatogenia de la IC es un proceso complejo&#44; en la que intervienen numerosos sistemas neurohormonales&#46; Por lo tanto&#44; el manejo terap&#233;utico debe centrarse en el tratamiento de los diferentes sistemas neurohormonales de manera global &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">23&#8211;29</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">De hecho&#44; en un reciente estudio que analiz&#243; los resultados combinados de varios ensayos cl&#237;nicos&#44; en comparaci&#243;n con el empleo de inhibidores de la enzima convertidora de angiotensina&#47;antagonistas de los receptores de angiotensina II m&#225;s betabloqueantes&#44; el tratamiento con sacubitrilo&#47;valsart&#225;n&#44; betabloqueantes&#44; antagonistas de la aldosterona y los inhibidores del cotransportador sodio-glucosa tipo 2 &#40;SGLT-2&#41; se asoci&#243; con reducciones significativas de los eventos cardiovasculares<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">30</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">En consecuencia&#44; es necesario iniciar de manera precoz todos aquellos f&#225;rmacos que hayan demostrado que mejoran el pron&#243;stico y&#44; de esta forma&#44; disminuir los eventos cardiovasculares en los pacientes con IC<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">31</span></a>&#46; Desafortunadamente&#44; un porcentaje sustancial de pacientes con IC no est&#225; tomando la combinaci&#243;n de tratamientos recomendados&#44; lo que se asocia con un incremento en el riesgo de presentar complicaciones<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">32</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Tradicionalmente las gu&#237;as de pr&#225;ctica cl&#237;nica de IC hab&#237;an presentado un enfoque vertical del tratamiento&#44; a&#241;adiendo&#47;modificando el tratamiento si persisten los s&#237;ntomas<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">33</span></a>&#46; Sin embargo&#44; este planteamiento supone un retraso en la optimizaci&#243;n del tratamiento&#44; lo que potencialmente podr&#237;a suponer un peor pron&#243;stico a largo plazo<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">34&#44;35</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">En cambio&#44; las nuevas recomendaciones han cambiado este enfoque&#44; pasando de un planteamiento secuencial y &#171;vertical&#187; del tratamiento&#44; a uno m&#225;s &#171;transversal&#187;&#44; con el objetivo&#44; precisamente&#44; de que el paciente obtenga el m&#225;ximo beneficio desde el principio<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">24&#8211;26</span></a>&#46; As&#237;&#44; las &#250;ltimas gu&#237;as europeas de IC del a&#241;o 2021 recomiendan en pacientes sintom&#225;ticos con IC-FEr&#44; de primera l&#237;nea&#44; el empleo de sacubitrilo&#47;valsart&#225;n o inhibidores de la enzima convertidora de angiotensina&#44; betabloqueantes&#44; antagonistas de la aldosterona e inhibidores SGLT-2&#44; y&#44; de segunda l&#237;nea&#44; el uso de vericiguat&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">De hecho&#44; las gu&#237;as europeas de IC se&#241;alan que se deber&#237;a considerar el tratamiento con vericiguat en pacientes sintom&#225;ticos&#44; que presenten empeoramiento de IC a pesar de los tratamientos de primera l&#237;nea para reducir el riesgo de muerte cardiovascular u hospitalizaci&#243;n por IC &#40;recomendaci&#243;n IIb&#44; nivel de evidencia B&#41;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">24</span></a>&#46; La Agencia Europea del Medicamento ha aprobado vericiguat para el tratamiento de la IC cr&#243;nica sintom&#225;tica en pacientes adultos con IC-FEr que est&#225;n estabilizados despu&#233;s de un episodio reciente de descompensaci&#243;n que requiri&#243; tratamiento diur&#233;tico por v&#237;a intravenosa<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">36</span></a>&#46; Sin embargo&#44; es importante destacar que&#44; a pesar de los tratamientos de primera l&#237;nea&#44; el riesgo residual de eventos sigue siendo elevado<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">37</span></a>&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Por lo tanto&#44; sigue siendo necesario el empleo de nuevos tratamientos&#44; como vericiguat&#44; que act&#250;en sobre v&#237;as fisiopatol&#243;gicas complementarias&#44; que ayuden a disminuir la carga de enfermedad que supone la IC&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Vericiguat&#58; mecanismo de acci&#243;n y par&#225;metros farmacocin&#233;ticos</span><p id="par0055" class="elsevierStylePara elsevierViewall">En la IC existe una alteraci&#243;n de la s&#237;ntesis del &#243;xido n&#237;trico&#44; as&#237; como una disminuci&#243;n de la actividad de su receptor&#44; la guanilato ciclasa soluble &#40;GCs&#41;&#44; lo que a su vez provoca una deficiencia del guanos&#237;n monofosfato c&#237;clico &#40;GMPc&#41;&#46; La deficiencia de GMPc provoca un deterioro de la funci&#243;n mioc&#225;rdica&#44; vascular y renal&#46; Ninguno de los tratamientos actuales de la IC &#40;betabloqueantes&#44; inhibidores del sistema renina-angiotensina&#44; inhibidores SGLT-2&#41; act&#250;an por esta v&#237;a&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Vericiguat es un f&#225;rmaco oral que estimula de manera directa la GCs&#44; lo que aumenta la disponibilidad de GMPc intracelular&#44; y de esta forma produce efectos beneficiosos&#44; restableciendo la deficiencia relativa en la v&#237;a de se&#241;alizaci&#243;n &#243;xido n&#237;trico-GCs-GMPc mediante la estimulaci&#243;n directa de la GCs&#44; de forma independiente y sin&#233;rgica con el &#243;xido n&#237;trico&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">El aumento de GMPc se traduce en una reducci&#243;n del remodelado del ventr&#237;culo izquierdo&#44; en una mejor&#237;a de la funci&#243;n mioc&#225;rdica y vascular&#44; adem&#225;s de en un descenso de la fibrosis y la inflamaci&#243;n &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">36&#44;38&#8211;45</span></a>&#46; En consecuencia&#44; a diferencia de otros f&#225;rmacos que inhiben determinadas v&#237;as delet&#233;reas que se encuentran activadas&#44; como el sistema renina-angiotensina-aldosterona o el sistema nervioso simp&#225;tico&#44; vericiguat y sacubitrilo estimulan las v&#237;as protectoras &#40;sistema &#243;xido n&#237;trico-GCs-GMPc y p&#233;ptidos natriur&#233;ticos&#44; respectivamente&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">23&#8211;29</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">En cuanto a la farmacocin&#233;tica&#44; la biodisponibilidad absoluta de vericiguat es elevada cuando se toma con alimentos &#40;93&#37;&#41;&#44; por lo que se recomienda su toma con los mismos&#46; La uni&#243;n a prote&#237;nas plasm&#225;ticas es de aproximadamente el 98&#37;&#44; principalmente con la alb&#250;mina&#46; Con respecto al metabolismo&#44; la glucuronidaci&#243;n a trav&#233;s de UGT1A9 y UGT1A1 es la v&#237;a principal de biotransformaci&#243;n&#44; mientras que el metabolismo mediado por el citocromo P 450 es peque&#241;o &#40;&#60;<span class="elsevierStyleHsp" style=""></span>5&#37;&#41;&#44; por lo que el riesgo de interacciones farmacocin&#233;ticas con otros f&#225;rmacos es bajo&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">No obstante&#44; est&#225; contraindicado el empleo concomitante de vericiguat con otros estimuladores de la GCs&#44; como riociguat&#46; La vida media en los sujetos sanos es de unas 20<span class="elsevierStyleHsp" style=""></span>h&#44; llegando hasta 30<span class="elsevierStyleHsp" style=""></span>h en los pacientes con IC&#46; Aproximadamente el 53&#37; se excreta en la orina y el 45&#37; en las heces&#46; No es necesario ajustar la dosis en funci&#243;n de la edad&#44; el sexo&#44; la raza&#44; el peso corporal&#44; o los niveles basales de p&#233;ptidos natriur&#233;ticos&#46; Tampoco es necesario ajustar la dosis en sujetos con un filtrado glomerular<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; o con insuficiencia hep&#225;tica leve o moderada&#46; Sin embargo&#44; no se ha estudiado el uso de vericiguat en sujetos con enfermedad renal m&#225;s avanzada o insuficiencia hep&#225;tica grave<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">36&#44;46&#8211;50</span></a>&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Desarrollo cl&#237;nico de vericiguat</span><p id="par0080" class="elsevierStylePara elsevierViewall">En el desarrollo cl&#237;nico de vericiguat destacan principalmente 4 ensayos cl&#237;nicos&#44; 2 en fase II &#40;SOCRATES &#91;SOluble guanylate Cyclase stimulatoR in heArT failurE Study&#93;-REDUCED y SOCRATES-PRESERVED&#41; y 2 en fase III &#40;VICTORIA &#91;Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction&#93; y VITALITY &#91;Evaluate the Efficacy and Safety of the Oral sGC Stimulator Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients with Heart Failure and Preserved Ejection Fraction&#93;&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">El programa fase II SOCRATES est&#225; formado por 2 ensayos cl&#237;nicos&#44; multic&#233;ntricos&#44; de grupos paralelos y controlados con placebo&#58; el estudio SOCRATES-REDUCED&#44; en pacientes con FEVI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>45&#37; y el SOCRATES-PRESERVED&#44; en sujetos con FEVI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>45&#37;&#44; que analizaron los efectos farmacodin&#225;micos&#44; farmacocin&#233;ticos&#44; seguridad y tolerabilidad de 4 dosis diferentes de vericiguat durante 12 semanas&#44; al alta o tras 4 semanas de una hospitalizaci&#243;n por IC&#46; La variable primaria del estudio SOCRATES-REDUCED fue el cambio en los niveles de prop&#233;ptido natriur&#233;tico cerebral N-terminal &#40;NT-proBNP&#41;&#44; y del SOCRATES-PRESERVED&#44; el cambio en los niveles de NT-proBNP y el volumen de la aur&#237;cula izquierda&#44; tras 12 semanas de tratamiento<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">51</span></a>&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">En el estudio SOCRATES-REDUCED se incluyeron a 456 pacientes&#58; 92 en el grupo placebo y 91 en cada grupo de vericiguat &#40;1&#44;25<span class="elsevierStyleHsp" style=""></span>mg&#59; 2&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#59; 5<span class="elsevierStyleHsp" style=""></span>mg y 10<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46; Aunque globalmente no hubo diferencias significativas con respecto a los cambios en los niveles de p&#233;ptidos natriur&#233;ticos de vericiguat en comparaci&#243;n con placebo&#44; s&#237; se observ&#243; una relaci&#243;n de dosis respuesta de vericiguat &#40;a mayor dosis&#44; mayor reducci&#243;n&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41;&#46; Aunque este estudio no ten&#237;a potencia suficiente para valorar los eventos cl&#237;nicos&#44; las tasas de mortalidad y hospitalizaci&#243;n por IC fueron num&#233;ricamente m&#225;s bajas con vericiguat que con el placebo &#40;11&#37; y 12&#44;1&#37; con vericiguat 10<span class="elsevierStyleHsp" style=""></span>mg y 5<span class="elsevierStyleHsp" style=""></span>mg&#44; respectivamente&#44; frente a 19&#44;6&#37; en el grupo placebo&#41;&#46; Adem&#225;s&#44; la tolerancia de vericiguat fue buena<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">52</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">En el estudio SOCRATES-PRESERVED&#44; si bien el tratamiento con vericiguat no se asoci&#243; con cambios significativos ni en los niveles de NT-proBNP&#44; ni en el volumen de la aur&#237;cula izquierda&#44; s&#237; se observ&#243; una mejor&#237;a en la calidad de vida y en el estado de salud de los pacientes tratados con vericiguat&#44; adem&#225;s de su buena tolerancia<a class="elsevierStyleCrossRefs" href="#bib0625"><span class="elsevierStyleSup">53&#44;54</span></a>&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">El estudio VICTORIA fue un ensayo cl&#237;nico fase III&#44; aleatorizado&#44; doble ciego&#44; de grupos paralelos&#44; controlado con placebo&#44; realizado con el objetivo de evaluar los efectos de vericiguat en pacientes con IC cr&#243;nica sintom&#225;tica tras un evento de empeoramiento de IC&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Se incluyeron pacientes con IC-FEr &#40;FEVI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>45&#37;&#41;&#44; en clase funcional II-IV la <span class="elsevierStyleItalic">New York Heart Association</span>&#44; niveles de p&#233;ptidos natriur&#233;ticos elevados &#40;p&#233;ptido natriur&#233;tico cerebral &#40;BNP&#41;<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>pg&#47;mL o NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>1000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL si ritmo sinusal&#59; BNP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>pg&#47;mL o NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>1600<span class="elsevierStyleHsp" style=""></span>pg&#47;mL si fibrilaci&#243;n auricular&#41;&#44; filtrado glomerular estimado<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; y hospitalizaci&#243;n por IC en los 6 meses previos o tratamiento diur&#233;tico intravenoso &#40;iv&#41; para la IC en los 3 meses previos&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Los pacientes fueron aleatorizados para recibir vericiguat &#40;dosis inicial 2&#44;5<span class="elsevierStyleHsp" style=""></span>mg una vez al d&#237;a&#44; dosis objetivo 10<span class="elsevierStyleHsp" style=""></span>mg una vez al d&#237;a&#41; o placebo&#44; a&#241;adidos a la terapia est&#225;ndar de la IC&#46; La variable primaria del estudio fue la combinaci&#243;n de muerte cardiovascular o primera hospitalizaci&#243;n por IC<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#46; Las caracter&#237;sticas basales de los pacientes se muestran en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#46; En el 89&#44;2&#37; de los casos se consigui&#243; la dosis objetivo de vericiguat<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Tras una mediana de seguimiento de 10&#44;8 meses&#44; el tratamiento con vericiguat se asoci&#243; con una reducci&#243;n significativa de la variable primaria del 10&#37; &#40;<span class="elsevierStyleItalic">hazard ratio</span> &#91;HR&#93; 0&#44;90&#59; intervalo de confianza 95&#37; &#91;IC95&#37;&#93; 0&#44;82-0&#44;98&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41;&#46; Adem&#225;s&#44; tambi&#233;n se objetivaron con vericiguat reducciones significativas de las hospitalizaciones totales por IC y de la variable combinada hospitalizaci&#243;n por IC o muerte por cualquier causa &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46; Los resultados de la variable primaria fueron consistentes en los diferentes subgrupos de pacientes analizados &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Aunque el riesgo de la variable primaria aumentaba conforme m&#225;s pr&#243;xima hab&#237;a sido la hospitalizaci&#243;n por IC y disminu&#237;a en los pacientes m&#225;s cr&#243;nicos&#44; el beneficio de vericiguat se mantuvo en todos los pacientes&#44; si bien hubo una tendencia a que este fuera mayor cuanto m&#225;s tiempo hab&#237;a pasado desde la hospitalizaci&#243;n &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;09&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Igualmente&#44; parece que el beneficio de vericiguat en cuanto a la variable primaria y a sus dos componentes por separado fue mayor en los sujetos con NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>8000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL &#40;86&#37; de la poblaci&#243;n VICTORIA&#41;&#46; De igual forma&#44; el beneficio de vericiguat fue independiente del tratamiento para la IC que tomase el paciente&#44; analizados de manera aislada o en combinaci&#243;n&#46; Adem&#225;s&#44; el tratamiento con vericiguat no se asoci&#243; con un deterioro de la funci&#243;n renal&#44; y la eficacia y seguridad fueron independientes del filtrado glomerular<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">28&#44;38&#44;55&#8211;58</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">En cuanto al riesgo de efectos secundarios&#44; los eventos adversos graves fueron similares en ambos grupos&#46; La hipotensi&#243;n sintom&#225;tica ocurri&#243; en el 9&#44;1&#37; de los pacientes tratados con vericiguat y en el 7&#44;9&#37; de los pacientes del grupo placebo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;12&#41;&#44; y el s&#237;ncope ocurri&#243; en el 4&#37; y 3&#44;5&#37; de los pacientes&#44; respectivamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;30&#41;&#46; La presi&#243;n arterial sist&#243;lica descendi&#243; ligeramente en ambos brazos de tratamiento durante las primeras 16 semanas del estudio y luego volvi&#243; a los niveles basales&#46; Se describieron m&#225;s casos de anemia con vericiguat &#40;7&#44;6&#37; y 5&#44;7&#37;&#44; respectivamente&#41;&#44; de los que 1&#44;6&#37; y 0&#44;9&#37; fueron considerados como efectos adversos graves<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">El estudio VITALITY se dise&#241;&#243; para conocer la eficacia y seguridad de vericiguat sobre la calidad de vida y la tolerancia al ejercicio en pacientes con IC y FEVI preservada&#46; Se incluyeron a 789 pacientes con IC cr&#243;nica y FE<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>45&#37;&#44; clase funcional de la <span class="elsevierStyleItalic">New York Heart Association</span> II o III&#44; con descompensaci&#243;n reciente en los 6 meses previos &#40;hospitalizaci&#243;n por IC o necesidad de diur&#233;ticos iv para IC sin hospitalizaci&#243;n&#41; y p&#233;ptidos natriur&#233;ticos elevados&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Los pacientes fueron aleatorizados para recibir vericiguat titulado hasta 15<span class="elsevierStyleHsp" style=""></span>mg &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>264&#41; o 10<span class="elsevierStyleHsp" style=""></span>mg &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>263&#41;&#44; o a placebo &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>262&#41;&#46; No se encontraron diferencias significativas ni en las puntuaciones de limitaci&#243;n f&#237;sica del cuestionario Kansas City&#44; ni en la prueba de los 6 minutos entre los grupos&#44; tras 24 semanas de tratamiento<a class="elsevierStyleCrossRefs" href="#bib0655"><span class="elsevierStyleSup">59&#44;60</span></a>&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Papel de vericiguat en el tratamiento de los pacientes con insuficiencia card&#237;aca</span><p id="par0145" class="elsevierStylePara elsevierViewall">Las gu&#237;as europeas de IC de 2021 establecen como tratamientos de primera l&#237;nea en los pacientes con IC-FEr el uso de sacubitrilo-valsart&#225;n o inhibidores de la enzima convertidora de angiotensina&#44; betabloqueantes&#44; antagonistas de la aldosterona e inhibidores SGLT-2&#46; Vericiguat se encontrar&#237;a en un segundo escal&#243;n en los pacientes que continuasen sintom&#225;ticos&#44; principalmente tras una descompensaci&#243;n reciente<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">24</span></a>&#46; Estas recomendaciones se basan fundamentalmente en los ensayos cl&#237;nicos pivotales de estos f&#225;rmacos&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Sin embargo&#44; dado que en estos momentos no hay un ensayo cl&#237;nico que compare la eficacia de los diferentes tratamientos para la IC entre s&#237;&#44; y solo se pueden hacer comparaciones indirectas entre estos estudios&#44; es importante hacer un an&#225;lisis cr&#237;tico<a class="elsevierStyleCrossRefs" href="#bib0665"><span class="elsevierStyleSup">61&#44;62</span></a>&#46; Comparar los resultados de los ensayos cl&#237;nicos empleando &#250;nicamente la HR es claramente insuficiente&#44; y exige una valoraci&#243;n global de los estudios&#44; considerando su dise&#241;o&#44; el perfil de riesgo de los pacientes incluidos&#44; la duraci&#243;n del estudio&#44; as&#237; como las reducciones absolutas y relativas de riesgo&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">En este contexto&#44; y considerando el diferente perfil de riesgo de los pacientes&#44; m&#225;s que comparar los HR&#44; las diferencias absolutas de riesgo anualizadas podr&#237;an aportar una informaci&#243;n m&#225;s relevante<a class="elsevierStyleCrossRefs" href="#bib0665"><span class="elsevierStyleSup">61&#44;62</span></a>&#46; As&#237; por ejemplo&#44; mientras que las reducciones relativas en los estudios PARADIGM HF&#44; DAPA-HF y EMPEROR-Reduced fueron superiores que la obtenida en el estudio VICTORIA&#44; las reducciones absolutas de riesgo fueron similares para vericiguat y los inhibidores SGLT-2 y superiores a las obtenidas por sacubitrilo&#47;valsart&#225;n&#44; considerando adem&#225;s que los pacientes incluidos en el estudio VICTORIA fueron los de mayor riesgo en comparaci&#243;n con el resto de los estudios contempor&#225;neos para la IC&#46; De hecho&#44; el n&#250;mero necesario de pacientes a tratar para la variable primaria fue de 24 pacientes para vericiguat y de 37 pacientes para sacubitrilo&#47;valsart&#225;n &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;<a class="elsevierStyleCrossRefs" href="#bib0635"><span class="elsevierStyleSup">55&#44;63&#8211;65</span></a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0160" class="elsevierStylePara elsevierViewall">En consecuencia&#44; es necesario ir m&#225;s all&#225; de las gu&#237;as de pr&#225;ctica cl&#237;nica<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">66</span></a> y realizar un enfoque terap&#233;utico individualizado&#44; empleando aquellos f&#225;rmacos que hayan demostrado beneficio cl&#237;nico&#44; basado en las caracter&#237;sticas de cada paciente &#40;presi&#243;n arterial&#44; frecuencia card&#237;aca&#44; funci&#243;n renal&#44; niveles de potasio s&#233;rico&#44; etc&#46;&#41; y no solo en las diferencias relativas de ensayos cl&#237;nicos diferentes<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">67</span></a>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">En cuando al modo de empleo de vericiguat&#44; la dosis inicial recomendada es de 2&#44;5<span class="elsevierStyleHsp" style=""></span>mg de vericiguat una vez al d&#237;a&#44; duplicando la dosis aproximadamente cada 2 semanas hasta llegar a la dosis objetivo de mantenimiento de 10<span class="elsevierStyleHsp" style=""></span>mg una vez al d&#237;a&#44; en funci&#243;n de la tolerancia del paciente&#46; El tratamiento se asocia con una reducci&#243;n discreta de la presi&#243;n arterial sist&#243;lica en comparaci&#243;n con placebo &#40;1-2<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#44; y no es necesario realizar una monitorizaci&#243;n de los electr&#243;litos&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">No se recomienda iniciar vericiguat en pacientes con una presi&#243;n arterial sist&#243;lica<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mmHg&#46; En caso de hipotensi&#243;n sintom&#225;tica&#44; se recomienda reducir&#47;suspender la dosis de vericiguat&#44; seg&#250;n los casos&#46; No se esperan interacciones farmacol&#243;gicas relevantes&#44; si bien se recomienda no emplear con los inhibidores de la fosfodiesterasa 5 de manera concomitante&#46; Antes de comenzar el tratamiento con vericiguat tras un episodio de descompensaci&#243;n de IC&#44; se recomienda optimizar el estado vol&#233;mico&#47;diur&#233;tico&#44; en particular en aquellos pacientes con niveles de NT-proBNP muy elevados<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">36</span></a>&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Con respecto al empleo de vericiguat en los sujetos con IC-FE preservada&#44; los resultados son todav&#237;a limitados&#44; y por lo tanto se necesitan m&#225;s estudios para posicionar adecuadamente este f&#225;rmaco en esta entidad&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Discusi&#243;n</span><p id="par0180" class="elsevierStylePara elsevierViewall">A pesar de las mejoras obtenidas en los &#250;ltimos a&#241;os con los tratamientos actuales&#44; el paciente con IC y&#44; especialmente&#44; aquellos que han tenido una descompensaci&#243;n reciente&#44; todav&#237;a presentan un riesgo elevado de hospitalizaci&#243;n por IC y de muerte durante el seguimiento<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">7&#8211;9</span></a>&#46; Aunque el paciente mantenga cierta &#171;estabilidad&#187; cl&#237;nica durante alg&#250;n tiempo&#44; la IC-FEr sigue progresando por la estimulaci&#243;n mantenida de las v&#237;as delet&#233;reas y la supresi&#243;n de las v&#237;as protectoras<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">15&#44;16</span></a>&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">En consecuencia&#44; el tratamiento de algunas de estas v&#237;as&#44; pero no de todas&#44; supone un tratamiento parcial e insuficiente&#44; que no impide la progresi&#243;n de la enfermedad&#46; Por lo tanto&#44; el foco del tratamiento de la IC se debe basar tanto en estimular las v&#237;as protectoras como en inhibir las v&#237;as delet&#233;reas&#46; Y en este sentido&#44; las gu&#237;as de pr&#225;ctica cl&#237;nica coinciden en la necesidad del tratamiento precoz con aquellos f&#225;rmacos que hayan demostrado beneficio pron&#243;stico<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">24&#8211;26</span></a>&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Vericiguat&#44; como agonista de GCs&#44; es capaz de estimular la v&#237;a protectora del &#243;xido n&#237;trico-GMPc<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">39&#8211;44</span></a>&#46; El estudio VICTORIA se enfoc&#243; en una poblaci&#243;n diferente a la incluida en los ensayos cl&#237;nicos contempor&#225;neos de la IC&#44; incluyendo sujetos con un mayor riesgo basal&#44; como son los pacientes con IC con FEVI<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>45&#37;&#44; y una descompensaci&#243;n reciente de IC &#40;hospitalizaci&#243;n en los 6 meses anteriores o intensificaci&#243;n con diur&#233;ticos iv en los 3 meses previos&#41;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#46; Por lo tanto&#44; este estudio va en l&#237;nea con las actuales gu&#237;as de pr&#225;ctica cl&#237;nica&#44; ya que da respuesta a aquellos pacientes que persisten sintom&#225;ticos a pesar del tratamiento inicial de la IC&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">En el estudio VICTORIA&#44; cerca del 90&#37; de los pacientes lograron la dosis objetivo de 10<span class="elsevierStyleHsp" style=""></span>mg de vericiguat&#44; lo que indica que es un f&#225;rmaco muy bien tolerado&#46; En este ensayo cl&#237;nico&#44; en el que los pacientes tomaban el tratamiento m&#233;dico &#243;ptimo para la IC recomendado por las gu&#237;as de pr&#225;ctica cl&#237;nica&#44; el tratamiento con vericiguat se tradujo en una reducci&#243;n significativa del 10&#37; del objetivo primario compuesto por muerte de causa cardiovascular o primera hospitalizaci&#243;n por IC&#44; con un NNT de 24&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Adem&#225;s&#44; hay una r&#225;pida separaci&#243;n de las curvas de eventos a los 4 meses que se mantiene hasta el final del seguimiento&#44; e incluso se observa una amplificaci&#243;n del beneficio<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#46; En consecuencia&#44; es un tratamiento cuyo beneficio va a aumentar si se inicia de manera precoz en los pacientes con IC-FEr y se mantiene en el tiempo&#46; Un reciente metaan&#225;lisis sobre la eficacia de los estimuladores GCs confirma este beneficio sobre los eventos cardiovasculares&#44; con un buen perfil de seguridad<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">68</span></a>&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Asimismo&#44; el beneficio de vericiguat es independiente del tratamiento concomitante para la IC&#44; incluyendo sacubitrilo&#47;valsart&#225;n&#44; as&#237; como del tiempo desde la hospitalizaci&#243;n o episodio de descompensaci&#243;n de IC<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#46; Esto implica que vericiguat se puede emplear independientemente del tratamiento de base que lleve el paciente&#44; y que se puede prescribir en pacientes con episodio previo de hospitalizaci&#243;n&#44; de descompensaci&#243;n reciente o de necesidad de intensificaci&#243;n de tratamiento&#44; as&#237; como en la consulta temprana tras el alta hospitalaria&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Por lo tanto&#44; vericiguat permite optimizar el tratamiento cuanto antes para obtener el m&#225;ximo beneficio&#46; Adem&#225;s&#44; es un f&#225;rmaco particularmente favorable en los pacientes con enfermedad renal cr&#243;nica &#40;en el estudio VICTORIA se incluyeron a pacientes con filtrado glomerular<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>15<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; dado que vericiguat no produce alteraciones ni de la funci&#243;n renal ni trastornos hidroelectrol&#237;ticos&#46; Tambi&#233;n cabe destacar que la eficacia y seguridad del f&#225;rmaco son independientes de la funci&#243;n renal<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">36&#44;55</span></a>&#46; Ahora bien&#44; dado que el m&#225;ximo beneficio de vericiguat se obten&#237;a en pacientes con niveles de NT-proBNP<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>8&#46;000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#44; es posible que haya que intensificar el tratamiento deplectivo antes de comenzar el tratamiento con vericiguat en aquellos sujetos con cifras de p&#233;ptidos natriur&#233;ticos superiores a estos niveles&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Vericiguat tiene un excelente perfil de seguridad y el hecho de que no sea necesario determinar la funci&#243;n renal y los iones plasm&#225;ticos hacen que sea un f&#225;rmaco sencillo de emplear y titular en la consulta diaria&#44; incluyendo la teleconsulta&#44; tan importante en el manejo del paciente con IC<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">69</span></a>&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Finalmente&#44; se ha estimado que el empleo de vericiguat en la pr&#225;ctica cl&#237;nica ser&#237;a coste-efectivo&#44; ya que vericiguat produce una reducci&#243;n significativa de las hospitalizaciones por IC &#40;primer episodio y recurrencias&#41;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">70</span></a>&#44; que son el principal condicionante para el aumento de los costes sanitarios asociados a la IC<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">14</span></a>&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">En definitiva&#44; vericiguat se ha mostrado como un tratamiento eficaz y seguro en una poblaci&#243;n que presenta un n&#250;mero muy elevado de eventos en un corto per&#237;odo de tiempo&#44; como son los pacientes con IC-FEr y una descompensaci&#243;n reciente por IC&#44; en los que es necesario un tratamiento precoz&#44; transversal e integral&#46; Su sencillez en el manejo y titulaci&#243;n facilitar&#237;an su uso en la pr&#225;ctica cl&#237;nica habitual&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">Con respecto a los pacientes con IC-FE preservada&#44; los resultados con vericiguat&#44; al igual que con otros estimuladores de la GCs son discretos&#44; por lo que en el momento actual no se puede recomendar en esta entidad<a class="elsevierStyleCrossRefs" href="#bib0625"><span class="elsevierStyleSup">53&#44;54&#44;60&#44;71&#44;72</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Financiaci&#243;n</span><p id="par0235" class="elsevierStylePara elsevierViewall">Los autores no han recibido financiaci&#243;n para la elaboraci&#243;n de este manuscrito&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conflicto de intereses</span><p id="par0240" class="elsevierStylePara elsevierViewall">J&#46;R&#46; Gonz&#225;lez-Juanatey reporta honorarios por conferencias y consejo asesor de Bayer&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">M&#46; Anguita-S&#225;nchez ha recibido financiaci&#243;n por servicios de consultor&#237;a y conferencias de Bayer&#44; Daiichi- Sankyo y Pfizer&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">A&#46; Bayes-Gen&#237;s ha recibido financiaci&#243;n por servicios de consultor&#237;a y conferencias de AstraZeneca&#44; Abbott&#44; Boehringer-Ingelheim&#44; Lilly&#44; Novartis&#44; Vifor&#44; Roche Diagnostics&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">J&#46; Com&#237;n-Colet reporta honorarios por conferencias y consejo asesor de Bayer&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">A&#46; Garc&#237;a-Quintana ha recibido financiaci&#243;n por servicios de consultor&#237;a y conferencias de Bayer&#44; Daiichi-Sankyo&#44; Pfizer&#44; Astra Zeneca&#44; Boerhinger Ingelheim&#44; Novartis y Rovi&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">A&#46; Recio-Mayoral ha recibido financiaci&#243;n por servicios de consultor&#237;a y conferencias de Bayer&#44; Janssen&#44; MSD&#44; Novartis y Vifor&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">J&#46;L&#46; Zamorano-G&#243;mez reporta honorarios por conferencias de Bayer&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">J&#46;M&#46; Cepeda ha recibido honorarios por servicios de consultor&#237;a y &#47; o conferencias de Bayer&#44; Daiichi-Sankyo y BMS-Pfizer&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">L&#46; Manzano ha recibido retribuciones por servicios de consultor&#237;a y conferencias de Bayer&#44; Daiichi-Sankyo y BMS-Pfizer&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Agradecimientos</span><p id="par0285" class="elsevierStylePara elsevierViewall">Content Ed Net &#40;Madrid&#44; Espa&#241;a&#41; proporcion&#243; asistencia en la redacci&#243;n y la edici&#243;n con financiaci&#243;n de Bayer Hispania&#46;</p></span></span>"
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            0 => "cGMP"
            1 => "Heart failure"
            2 => "Nitric oxide"
            3 => "Vericiguat"
          ]
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    "resumen" => array:2 [
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A pesar de los tratamientos actuales&#44; el riesgo de muerte y hospitalizaciones en pacientes con insuficiencia card&#237;aca con fracci&#243;n de eyecci&#243;n reducida &#40;IC-FEr&#41; sigue siendo elevado&#46; La fisiopatolog&#237;a de la IC-FEr incluye activaci&#243;n neurohormonal caracterizada por la estimulaci&#243;n de las v&#237;as delet&#233;reas &#40;sistemas simp&#225;tico y renina-angiotensina-aldosterona&#41; y la supresi&#243;n de las v&#237;as protectoras como las dependientes del &#243;xido n&#237;trico&#46; La inhibici&#243;n o estimulaci&#243;n de algunas de estas v&#237;as&#44; pero no de todas&#44; es insuficiente&#46; En la IC-FEr existe una menor actividad de &#243;xido n&#237;trico&#44; guanilato ciclasa soluble y GMPc que provoca efectos delet&#233;reos a nivel mioc&#225;rdico&#44; vascular y renal&#46; Vericiguat estimula la actividad de esta v&#237;a protectora&#46; El estudio VICTORIA demostr&#243;&#44; en pacientes con IC-FEr y descompensaci&#243;n reciente&#44; que la adici&#243;n de vericiguat al tratamiento m&#233;dico &#243;ptimo reduc&#237;a de forma significativa la incidencia del objetivo primario compuesto de muerte cardiovascular u hospitalizaci&#243;n por IC&#44; con un n&#250;mero de 24 pacientes que es necesario tratar&#44; y una excelente tolerabilidad&#46;</p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Despite currently available treatments&#44; risk of death and hospitalizations in patients with heart failure with reduced ejection fraction &#40;HFrEF&#41; remains high&#46; The pathophysiology of HFrEF includes neurohormonal activation characterized by stimulation of deleterious pathways &#40;i&#46;e&#46;&#44; sympathetic nervous and renin-angiotensin-aldosterone systems&#41; and suppression of protective pathways such as nitric oxide-dependent pathways&#46; Inhibition or stimulation of some&#44; but not all&#44; of these pathways is insufficient&#46; In HFrEF&#44; there is reduced nitric oxide&#44; soluble guanylate cyclase&#44; and cGMP activity&#44; leading to deleterious effects in the myocardial&#44; vascular&#44; and renal systems&#46; Vericiguat is able to stimulate the activity of this protective pathway&#46; The VICTORIA study demonstrated that the addition of vericiguat to optimal medical treatment in patients with HFrEF and recent decompensation significantly reduced the incidence of the primary endpoint&#44; a composite of cardiovascular death or HF hospitalization&#44; with a number needed to treat of 24 patients and excellent tolerability&#46;</p></span>"
      ]
    ]
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          "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Mecanismo de acci&#243;n de vericiguat&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Figura adaptada de Armstrong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">28</span></a>&#44; Gheorghiade et al&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">39</span></a>&#44; Breitenstein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">43</span></a> y Follmann et al&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">44</span></a>&#46;</p>"
        ]
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      1 => array:7 [
        "identificador" => "fig0010"
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        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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          "es" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Eventos principales en el estudio VICTORIA&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">CV&#58; cardiovascular&#59; HR&#58; <span class="elsevierStyleItalic">hazard ratio</span>&#59; IC&#58; insuficiencia card&#237;aca&#46;</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">&#42;Muerte cardiovascular o primera hospitalizaci&#243;n por insuficiencia card&#237;aca&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Adaptada de Armstrong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#46;</p>"
        ]
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">ARA II&#58; antagonistas de los receptores de angiotensina II&#59; IC&#58; insuficiencia card&#237;aca&#59; IECA&#58; inhibidores de la enzima convertidora de angiotensina&#59; SGLT-2&#58; cotransportador de sodio-glucosa tipo 2&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sistemas implicados&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Sistema renina-angiotensina-aldosterona&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">Activaci&#243;n&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">Inhibidores sistema renina-angiotensina-aldosterona&#58; IECA&#44; ARA II&#44; antagonistas de la aldosterona&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">Sistema nervioso simp&#225;tico&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Activaci&#243;n&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">Betabloqueantes&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">P&#233;ptidos natriur&#233;ticos&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">Inhibici&#243;n&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">Inhibidores de la neprilisina&#58; activaci&#243;n p&#233;ptidos natriur&#233;ticos&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">SGLT-2&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">Activaci&#243;n<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  " align="left" valign="\n
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                  \t\t\t\t">Inhibidores SGLT-2<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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">Guanilato ciclasa&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">Inhibici&#243;n&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">Activaci&#243;n guanilato ciclasa&#58; vericiguat&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">No se conocen bien los mecanismos por los que los inhibidores SGLT-2 ofrecen un mecanismo cardioprotector&#46; Se incluyen factores hemodin&#225;micos&#44; control de la estimulaci&#243;n simp&#225;tica&#44; inhibici&#243;n de la fibrosis y del remodelado card&#237;aco&#44; mejora del gasto card&#237;aco&#44; modulaci&#243;n de las concentraciones citos&#243;licas de sodio y calcio y alteraciones de los niveles de adipocinas&#46;</p> <p class="elsevierStyleNotepara" id="npar0010">Adaptada de Triposkiadis et al&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">23</span></a>&#44; McDonagh et al&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">24</span></a>&#44; Maddox et al&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">25</span></a>&#44; McDonald et al&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">26</span></a>&#44; Matsumura y Sugiura<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">27</span></a>&#44; Armstrong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">28</span></a> y Nightingale<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">29</span></a>&#46;</p>"
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Etiopatogenia de la insuficiencia card&#237;aca y tratamientos potenciales</p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">ARA II&#58; antagonistas de los receptores de angiotensina II&#59; DAI&#58; desfibrilador autom&#225;tico implantable&#59; FEVI&#58; fracci&#243;n de eyecci&#243;n del ventr&#237;culo izquierdo&#59; IC&#58; insuficiencia card&#237;aca&#59; IECA&#58; inhibidores de la enzima convertidora de angiotensina&#59; NYHA&#58; <span class="elsevierStyleItalic">New York Heart Association</span>&#59; TRC&#58; terapia de resincronizaci&#243;n card&#237;aca&#59; iv&#58; intravenoso&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Adaptada de Armstrong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#46;</p>"
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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\ttable-head\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  " align="left" valign="\n
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                  \t\t\t\t">67&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;12&#44;2&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\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;921 &#40;76&#44;0&#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">1&#46;921 &#40;76&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>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">0&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">2&#47;2&#46;523 &#40;0&#44;1&#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"><span class="elsevierStyleHsp" style=""></span>II&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
                  \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;497&#47;2&#46;523 &#40;59&#44;3&#41;&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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>III&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;010&#47;2&#46;523 &#40;40&#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  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Edad &#40;a&#241;os&#41;</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>&#60;<span class="elsevierStyleHsp" style=""></span>75&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&#47;669&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;84&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;75&#8211;0&#44;94&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>&#8805;<span class="elsevierStyleHsp" style=""></span>75&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">318&#47;303&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;04&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;88&#8211;1&#44;21&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="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Evento &#237;ndice</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>Diur&#233;ticos iv<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3 meses&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">96&#47;120&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;78&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;60&#8211;1&#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>Hospitalizaci&#243;n<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3 meses&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">660&#47;701&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;93&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;84&#8211;1&#44;04&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>Hospitalizaci&#243;n 3&#8211;6 meses&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">141&#47;151&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><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;67&#8211;1&#44;07&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="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Filtrado glomerular basal &#40;mL&#47;min&#47;1&#44;73</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#41;</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>&#8804;<span class="elsevierStyleHsp" style=""></span>30&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">143&#47;128&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;06&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;83&#8211;1&#44;34&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>&#62;<span class="elsevierStyleHsp" style=""></span>30 a &#8804;<span class="elsevierStyleHsp" style=""></span>60&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">392&#47;445&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;84&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;73&#8211;0&#44;96&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>&#62;<span class="elsevierStyleHsp" style=""></span>60&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&#47;372&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;92&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;80&#8211;1&#44;07&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="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Clase funcional NYHA basal</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>Clase I&#47;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">445&#47;484&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;91&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;80&#8211;1&#44;04&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>Clase III&#47;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">451&#47;487&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;87&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;77&#8211;0&#44;99&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="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Uso de sacubitrilo&#47;valsart&#225;n basalmente</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>S&#237;&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">134&#47;153&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;88&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;70&#8211;1&#44;11&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>No&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">760&#47;818&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;90&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;81&#8211;0&#44;99&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="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">NT-proBNP basal por cuartiles &#40;pg&#47;mL&#41;</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>Q1 &#40;&#8804;<span class="elsevierStyleHsp" style=""></span>1556&#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">128&#47;161&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;78&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;62&#8211;0&#44;99&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>Q2 &#40;1556&#8211;2816&#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">165&#47;201&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</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hospitalizaci&#243;n IC<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>6 meses o diur&#233;ticos iv<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3 meses&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="elsevierStyleItalic">Caracter&#237;sticas basales</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>NT-proBNP &#40;mediana&#41;&#44; pg&#47;mL&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;608&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;437&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;906&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;816&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>Clase funcional NYHA III o IV&#44; &#37;&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41&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>Hospitalizaci&#243;n IC<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3 meses&#44; &#37;&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&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>Hospitalizaci&#243;n IC<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>6 meses&#44; &#37;&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&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>FGe&#44; mL&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&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>FGe<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>60 mL&#47;min&#47;1&#44;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; &#37;&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&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="elsevierStyleItalic">Eventos principales</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>Variable primaria&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primera hospitalizaci&#243;n por IC o muerte CV&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Empeoramiento IC &#40;hospitalizaci&#243;n no programada&#47;visita urgente que requiera tratamiento iv para IC&#41; o muerte CV&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primera hospitalizaci&#243;n por IC o muerte CV&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Primera hospitalizaci&#243;n por IC o muerte CV&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>Mediana de seguimiento &#40;meses&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&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>Tasa de eventos variable primaria en brazo control<a class="elsevierStyleCrossRef" href="#tblfn0010"><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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;2&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;6&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#44;0&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#44;8&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>Variable primaria&#44; HR &#40;IC 95&#37;&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;80 &#40;0&#44;73&#8211;0&#44;87&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;74 &#40;0&#44;65&#8211;0&#44;85&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;75 &#40;0&#44;65&#8211;0&#44;86&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;90 &#40;0&#44;82&#8211;0&#44;98&#41;&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>Muerte CV&#44; HR &#40;IC95&#37;&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;80 &#40;0&#44;71&#8211;0&#44;89&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;82 &#40;0&#44;69&#8211;0&#44;98&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;92 &#40;0&#44;75&#8211;1&#44;12&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;93 &#40;0&#44;81&#8211;1&#44;06&#41;&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>Primera hospitalizaci&#243;n por IC&#44; HR &#40;IC95&#37;&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;79 &#40;0&#44;71&#8211;0&#44;89&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;70 &#40;0&#44;59&#8211;0&#44;83&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;69 &#40;0&#44;59&#8211;0&#44;81&#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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;90 &#40;0&#44;81&#8211;1&#44;00&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2918464.png"
              ]
            ]
            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sac&#47;vals&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dapagliflozina&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Empagliflozina&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vericiguat&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><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="elsevierStyleItalic">Variable primaria</span>&#42;<a class="elsevierStyleCrossRef" href="#tblfn0010"><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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;2&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;5&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;6&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;6&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&#44;0&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;8&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#44;8&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#44;6&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>RAR&#47;NNT&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;7&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&#44;0&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;0&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#44;0&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#44;2&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#44;2&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;2&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;8&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="elsevierStyleItalic">Muerte CV</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;5&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;0&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;9&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;5&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;1&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;6&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#44;9&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#44;9&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>RAR&#47;NNT&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#44;7&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;4&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#44;4&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;6&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">166&#44;7&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;0&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&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</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;2&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="center" valign="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">29&#44;1&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">25&#44;9&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;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;5&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;9&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#44;5&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="center" valign="\n
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                  \t\t\t\t">4&#44;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#44;8&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;2&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Eventos por 100 pacientes-a&#241;o&#46;</p> <p class="elsevierStyleNotepara" id="npar0020">Tabla realizada con datos de Armstrong et al&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">55</span></a>&#44; McMurray et al&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">63</span></a>&#44; McMurray et al&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">64</span></a> y Packer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">65</span></a>&#46;</p>"
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        "descripcion" => array:1 [
          "es" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas basales y eventos principales de los estudios PARADIGM HF&#44; DAPA-HF&#44; EMPEROR-Reduced y VICTORIA</p>"
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      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Bibliograf&#237;a"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:72 [
            0 => array:3 [
              "identificador" => "bib0365"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology of heart failure"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Groenewegen"
                            1 => "F&#46;H&#46; Rutten"
                            2 => "A&#46; Mosterd"
                            3 => "A&#46;W&#46; Hoes"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ejhf.1858"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Heart Fail"
                        "fecha" => "2020"
                        "volumen" => "22"
                        "paginaInicial" => "1342"
                        "paginaFinal" => "1356"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32483830"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
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