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Initiation, maintenance and withdrawal of disease-modifying treatment during an acute heart failure decompensation
Inicio, mantenimiento y retirada del tratamiento modificador de la enfermedad durante una descompensación por insuficiencia cardiaca aguda
a Servicio de Medicina Interna, Hospital de Olot, Olot, Girona, Spain
b Departament de Ciències Mèdiques, Universitat de Girona, Girona, Spain
c Grupo de Trabajo de Insuficiencia Cardiaca y Fibrilación Auricular, Sociedad Española de Medicina Interna, Spain
d Servicio de Medicina Interna, Hospital Universitari de Bellvitge, L’ Hospitalet del Llobregat, Barcelona, Spain
e Servicio de Medicina Interna, Hospital Universitario de Getafe, Getafe, Madrid, Spain
f Servicio de Medicina Interna, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
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Trullàs, F. Formiga, J. Casado, A. González-Franco" "autores" => array:4 [ 0 => array:4 [ "nombre" => "J.C." "apellidos" => "Trullàs" "email" => array:1 [ 0 => "jctv5153@comg.cat" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "F." "apellidos" => "Formiga" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 2 => array:3 [ "nombre" => "J." 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"apellidos" => "González-Franco" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital de Olot, Olot, Girona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departament de Ciències Mèdiques, Universitat de Girona, Girona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Grupo de Trabajo de Insuficiencia Cardiaca y Fibrilación Auricular, Sociedad Española de Medicina Interna, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitari de Bellvitge, L’ Hospitalet del Llobregat, Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario de Getafe, Getafe, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Inicio, mantenimiento y retirada del tratamiento modificador de la enfermedad durante una descompensación por insuficiencia cardiaca aguda" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">There is sufficient evidence to state that all patients with heart failure (HF) with reduced ejection fraction (HFrEF) should undergo disease-modifying therapy (including an angiotensin-converting enzyme inhibitor [ACEI], an angiotensin <span class="elsevierStyleSmallCaps">ii</span>-receptor blocker [ARB) or a dual angiotensin receptor-neprilysin inhibitor [ARNI], along with a beta-blocker and an aldosterone antagonist [AA]), provided the patient's clinical situation is stable and there are no contraindications or intolerance to any of these drugs. There is much less information and evidence on managing disease-modifying therapy when patients with HFrEF are admitted for decompensation. There is therefore greater variability in the decision to start, continue, withdraw or change these drugs during hospitalization for decompensated HF, which is subject to personal experience and expert opinion.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1–3</span></a> The aim of this study was to determine the management of long-term medication of HFrEF employed by the members of the Heart Failure Workgroup of the Spanish Society of Internal Medicine (SEMI). To this end, a survey was conducted in October 2018 of all members of the SEMI Heart Failure workgroup (through a questionnaire sent by email). The survey asked the following questions: (1) What is your standard practice with long-term medication of HFrEF during hospitalization (withdraw it, reduce the dosage or maintain the same dosage)? (2) Do you believe that withdrawing this medication during the hospitalization can affect the patient's prognosis?</p><p id="par0010" class="elsevierStylePara elsevierViewall">A total of 194 internal medicine specialists of the Heart Failure Workgroup responded to the survey (median age, 43 years; range 25–65 years). Twenty-four percent of these respondents mainly treat patients with HF (HF units, specialized HF clinics, etc.), and the remaining 76% reported treating all types of patients (including those with HF). The survey results for the first question are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. In most cases, the standard clinical practice was to maintain the long-term medication for HFrEF in the decompensation phase; however, in some cases, the standard dosage was reduced (more often for beta-blockers). Moreover, starting sacubitril/valsartan (or changing from an ACEI or an ARB) during hospitalization was considered a safe and appropriate strategy by most of those surveyed (especially before the discharge with the patient euvolemic or with <span class="elsevierStyleItalic">minimal</span> congestion).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">For the second question, most of those surveyed considered that the withdrawal of the long-term medication did affect the prognosis (77% for the beta-blockers and 74% for ACEI or ARB), with a lower percentage for AA (45%). Among those who considered that it did affect the prognosis, the considerable majority considered that withdrawing the long-term medication worsened the prognosis (91% in the case of beta-blockers, 96% in the case of ACEI or ARB and 91% for AA), and a small percentage considered that it improved the prognosis.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Few studies have focused on the management of long-term medication of HFrEF during the hospitalization phase. The few studies that have focused on the management of beta-blockers (most of which were observational, with only 1 clinical trial)<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> were included in a meta-analysis that concluded that withdrawing the beta-blockers was associated with increased hospital and short-term mortality.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> The evidence is scarcer for ACEI/ARB; however, a large observational study also indicated that their withdrawal resulted in a poorer prognosis.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> Finally, sacubitril/valsartan is the only drug of the ARNI family that is indicated for treating HFrEF since the publication of the PARADIGM-HF study,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> which included patients with HF in stable clinical situations. Two recent clinical trials (TRANSITION and PIONEER-HF) evaluated whether starting (or changing from ACEI/ARB to) this drug during hospitalization for decompensation is a safe strategy. The TRANSITION study compared the strategy of starting sacubitril/valsartan just before or just after the discharge for patients with acute HF, without congestion and with oral diuretic therapy.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> The PIONEER-HF study (published after the survey was performed) compared the strategy of starting sacubitril/valsartan (vs. enalapril) during the start of hospitalization with hemodynamically stable patients who were still congestive (with intravenous diuretic). The study showed the superiority of sacubitril/valsartan versus enalapril in the primary endpoint (reduction in NT-proBNP levels), although this effect was expected, having been described in the PARADIGM-HF study. Moreover, there were no differences in any of the adverse effects. It is important to mention, however, that the confidence intervals for the relative risk of the safety objectives were very wide. Finally, sacubitril/valsartan also showed superiority in the secondary endpoints (combination of clinical events including death, HF readmission, need for left ventricular assistance and inclusion in waiting lists for heart transplantation). However, these results should be interpreted with caution, given that they were not a main objective (but rather exploratory) of the study.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">7–9</span></a> Therefore, the results of the studies and the experience of the expert participants in this survey appear to indicate that hospitalization for acute HF is an appropriate moment for starting or maintaining the long-term medication of HFrEF, provided there are no absolute contraindications and that the patient is hemodynamically stable.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors declare having been paid for participating in lectures and symposiums sponsored by Novartis (all authors) and Rovi (FF, JC and AGF) or for consulting tasks for these laboratories.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:2 [ "identificador" => "xack432211" "titulo" => "Acknowledgements" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Trullàs JC, Formiga F, Casado J, González-Franco A. Inicio, mantenimiento y retirada del tratamiento modificador de la enfermedad durante una descompensación por insuficiencia cardiaca aguda. Rev Clin Esp. 2019;219:464–466.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>: AA, aldosterone antagonists; ACEI, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; HF-REF, heart failure with reduced ejection fraction.</p>" "tablatextoimagen" => array:2 [ 0 => 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 " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">In the absence of an absolute contraindication (shock, hypotension, heart block, hyperkalemia), what is the standard clinical practice with long-term medication for HF-REF during hospitalization for decompensation?</th></tr><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"> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Withdraw \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Maintain (same dosage) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Maintain (reduce dosage) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Other \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">Beta-blockers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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">ACEI/ARB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \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">Sacubitril-valsartan \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9%<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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">AA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8%<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2155281.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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">When a patient is admitted for decompensated HF, do you consider it appropriate and safe to start treatment with sacubitril/valsartan (in treatment-naïve patients) or change from ACEI/ARB to sacubitril/valsartan?</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">No, I only start the treatment in an outpatient manner (stable patient) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19% \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">Yes, but only before the discharge (euvolemic or with minimal congestion) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70% \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">Yes, with the patient hemodynamically stable (regardless of the degree of congestion) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2155282.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Change to ACEI or ARB.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Increase the dosage.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Management of long-term medication for heart failure with reduced ejection fraction during hospitalization.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Initiation, continuation switching, and withdrawal of heart failure medical therapies during hospitalization" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.A. Bhagat" 1 => "S.J. Greene" 2 => "M. Vaduganathan" 3 => "G.C. Fonarow" 4 => "J. Butler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jchf.2018.06.011" "Revista" => array:5 [ "tituloSerie" => "JACC Heart Fail" "fecha" => "2019" "volumen" => "7" "paginaInicial" => "1" "paginaFinal" => "12" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0055" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of beta-blocker withdrawal in acute decompensated heart failure: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K.W. Prins" 1 => "J.M. Neill" 2 => "J.O. Tyler" 3 => "P.M. Eckman" 4 => "S. 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Rizkala" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1409077" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2014" "volumen" => "371" "paginaInicial" => "993" "paginaFinal" => "1004" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25176015" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0075" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Wachter" 1 => "M. Senni" 2 => "J. Belohlavek" 3 => "E. Straburzynska-Migaj" 4 => "K.K. Witte" 5 => "Z. Kobalava" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ejhf.1498" "Revista" => array:2 [ "tituloSerie" => "Eur J Heart Fail" "fecha" => "2019" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0080" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Angiotensin-neprilysin inhibition in acute decompensated heart failure" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "PIONEER-HF Investigators" "etal" => true "autores" => array:6 [ 0 => "E.J. Velazquez" 1 => "D.A. Morrow" 2 => "A.D. DeVore" 3 => "C.I. Duffy" 4 => "A.P. Ambrosy" 5 => "K. McCague" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1812851" "Revista" => array:5 [ "tituloSerie" => "N Engl J Med" "fecha" => "2019" "volumen" => "380" "paginaInicial" => "539" "paginaFinal" => "548" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0085" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical outcomes in patients with acute decompensated heart failure randomly assigned to sacubitril/valsartan or enalapril in the PIONEER-HF Trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.A. Morrow" 1 => "E.J. Velazquez" 2 => "A.D. deVore" 3 => "A.S. Desai" 4 => "C.I. Duffy" 5 => "A.P. Ambrosy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/circulationaha.118.03933" "Revista" => array:5 [ "tituloSerie" => "Circulation" "fecha" => "2019" "volumen" => "139" "paginaInicial" => "2285" "paginaFinal" => "2288" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0090" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PIONEERing the in-hospital initiation of sacubitril-valsartan" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Jarcho" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMe1900139" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2019" "volumen" => "380" "paginaInicial" => "590" "paginaFinal" => "591" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30726696" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack432211" "titulo" => "Acknowledgements" "texto" => "<p id="par0030" class="elsevierStylePara elsevierViewall">The authors would like to thank the members of the Heart Failure and Atrial Fibrillation Workgroup of the Spanish Society of Internal Medicine for participating in the survey.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/22548874/0000021900000008/v1_201910300730/S2254887419301547/v1_201910300730/en/main.assets" "Apartado" => array:4 [ "identificador" => "71813" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Correspondence" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021900000008/v1_201910300730/S2254887419301547/v1_201910300730/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887419301547?idApp=WRCEE" ]
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