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Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.
Packer, Milton; McMurray, John J V; Desai, Akshay S; Gong, Jianjian; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Solomon, Scott D; Swedberg, Karl; Zile, Michael; Andersen, Karl; Arango, Juan Luis; Arnold, J Malcolm; Belohlávek, Jan; Böhm, Michael; Boytsov, Sergey; Burgess, Lesley J; Cabrera, Walter; Calvo, Carlos; Chen, Chen-Huan; Dukat, Andrej; Duarte, Yan Carlos; Erglis, Andrejs; Fu, Michael; Gomez, Efrain; Gonzàlez-Medina, Angel; Hagège, Albert A; Huang, Jun; Katova, Tzvetana; Kiatchoosakun, Songsak; Kim, Kee-Sik; Kozan, Ömer; Llamas, Edmundo Bayram; Martinez, Felipe; Merkely, Bela; Mendoza, Iván; Mosterd, Arend; Negrusz-Kawecka, Marta; Peuhkurinen, Keijo; Ramires, Felix J A; Refsgaard, Jens; Rosenthal, Arvo; Senni, Michele; Sibulo, Antonio S; Silva-Cardoso, José; Squire, Iain B; Starling, Randall C; Teerlink, John R; Vanhaecke, Johan.
Afiliación
  • Packer M; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • McMurray JJ; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Desai AS; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Gong J; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Lefkowitz MP; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Rizkala AR; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Rouleau JL; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Shi VC; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Solomon SD; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Swedberg K; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Zile M; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Andersen K; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Arango JL; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Arnold JM; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Belohlávek J; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Böhm M; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Boytsov S; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Burgess LJ; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Cabrera W; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Calvo C; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Chen CH; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Dukat A; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Duarte YC; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Erglis A; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Fu M; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Gomez E; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Gonzàlez-Medina A; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Hagège AA; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Huang J; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Katova T; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Kiatchoosakun S; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Kim KS; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Kozan Ö; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Llamas EB; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Martinez F; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Merkely B; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Mendoza I; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Mosterd A; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Negrusz-Kawecka M; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Peuhkurinen K; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Ramires FJ; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Refsgaard J; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Rosenthal A; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Senni M; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Sibulo AS; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Silva-Cardoso J; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Squire IB; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Starling RC; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Teerlink JR; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
  • Vanhaecke J; From the Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX (M.P.); BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK (J.J.V.M.); Brigham and Women's Hospital, Cardiovascular Medicine, MA (A.S.D., S.D.S.); Novartis Pharmaceutic
Circulation ; 131(1): 54-61, 2015 Jan 06.
Article en En | MEDLINE | ID: mdl-25403646
ABSTRACT

BACKGROUND:

Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND

RESULTS:

We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril.

CONCLUSIONS:

Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. CLINICAL TRIAL REGISTRATION URL http//www.clinicaltrials.gov. Unique identifier NCT01035255.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Tetrazoles / Inhibidores de la Enzima Convertidora de Angiotensina / Enalapril / Neprilisina / Progresión de la Enfermedad / Antagonistas de Receptores de Angiotensina / Aminobutiratos / Insuficiencia Cardíaca Tipo de estudio: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Circulation Año: 2015 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Tetrazoles / Inhibidores de la Enzima Convertidora de Angiotensina / Enalapril / Neprilisina / Progresión de la Enfermedad / Antagonistas de Receptores de Angiotensina / Aminobutiratos / Insuficiencia Cardíaca Tipo de estudio: Clinical_trials / Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Circulation Año: 2015 Tipo del documento: Article