Marc A Pfeffer1, Brian Claggett1, Eldrin F Lewis1, Christopher B Granger1, Lars Køber1, Aldo P Maggioni1, Douglas L Mann1, John J V McMurray1, Jean-Lucien Rouleau1, Scott D Solomon1, Philippe G Steg1, Otavio Berwanger1, Maja Cikes1, Carmine G De Pasquale1, Cara East1, Alberto Fernandez1, Karola Jering1, Ulf Landmesser1, Roxana Mehran1, Béla Merkely1, Freny Vaghaiwalla Mody1, Mark C Petrie1, Ivo Petrov1, Morten Schou1, Michele Senni1, David Sim1, Peter van der Meer1, Martin Lefkowitz1, Yinong Zhou1, Jianjian Gong1, Eugene Braunwald1. 1. From the Cardiovascular Division (M.A.P., B.C., S.D.S., K.J., E.B.) and the Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division (E.B.), Brigham and Women's Hospital and Harvard Medical School, Boston; the Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto (E.F.L.), and the Heart Failure and Preventive Cardiology Programs, Department of Veterans Affairs Greater Los Angeles, University of California, Los Angeles, Los Angeles (F.V.M.) - both in California; Duke University Medical Center, Durham, NC (C.B.G.); Rigshospitalet, Blegdamsvej, University of Copenhagen (L.K.), and the Department of Cardiology, Herlev-Gentofte University Hospital (M. Schou) - both in Copenhagen; National Association of Hospital Cardiologists Research Center, Florence (A.P.M.), and the Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo (M. Senni) - both in Italy; Washington University School of Medicine, St. Louis (D.L.M.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom (J.J.V.M., M.C.P.); Montreal Heart Institute, University of Montreal, Montreal (J.-L.R.); Université de Paris, Assistance Publique-Hôpitaux de Paris, French Alliance for Cardiovascular Trials and INSERM Unité 1148, Paris (P.G.S.); Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo (O.B.); the Department of Cardiovascular Diseases, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia (M.C.); the Department of Cardiovascular Medicine, Flinders Medical Centre, Adelaide, SA, Australia (C.G.D.P.); Baylor Soltero CV Research Center, Baylor Scott and White Heart and Vascular Hospital, Dallas (C.E.); Cardiology Service, Sanatorio Modelo Quilmes, Quilmes, Argentina (A.F.); the Department of Cardiology, German Center for Cardiovascular Research Partner Site Berlin, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin (U.L.); Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (R.M.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.M.); Acibadem City Clinic Cardiovascular Center, Sofia, Bulgaria (I.P.); National Heart Center Singapore, Singapore (D.S.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (P.M.); and Novartis, East Hanover, NJ (M.L., Y.Z., J.G.).
Abstract
BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. CONCLUSIONS: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).
BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. CONCLUSIONS: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).
Authors: Marc A Pfeffer; Brian Claggett; Eldrin F Lewis; Christopher B Granger; Lars Køber; Aldo P Maggioni; Douglas L Mann; John J V McMurray; Jean-Lucien Rouleau; Scott D Solomon; Philippe Gabriel Steg; Otavio Berwanger; Maja Cikes; Carmine G De Pasquale; Alberto Fernandez; Gerasimos Filippatos; Karola Jering; Ulf Landmesser; Venugopal Menon; Béla Merkely; Mark C Petrie; Ivo Petrov; Morten Schou; Michele Senni; David Sim; Peter van der Meer; Martin Lefkowitz; Yinong Zhou; Yi Wang; Eugene Braunwald Journal: Circulation Date: 2021-11-19 Impact factor: 29.690
Authors: Amil M Shah; Brian Claggett; Narayana Prasad; Guichu Li; Mayra Volquez; Karola Jering; Maja Cikes; Attila Kovacs; Wilfried Mullens; Jose C Nicolau; Lars Køber; Peter van der Meer; Pardeep S Jhund; Ghionul Ibram; Martin Lefkowitz; Yinong Zhou; Scott D Solomon; Marc A Pfeffer Journal: Circulation Date: 2022-09-09 Impact factor: 39.918
Authors: Stefan Frantz; Moritz Jens Hundertmark; Jeanette Schulz-Menger; Frank Michael Bengel; Johann Bauersachs Journal: Eur Heart J Date: 2022-07-14 Impact factor: 35.855