Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.

Nov 15, 2021

Contributor: 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 G Steg,Otavio Berwanger,Maja Cikes,Carmine G De Pasquale,Cara East,Alberto Fernandez,Karola Jering,Ulf Landmesser,Roxana Mehran,Béla Merkely,Freny Vaghaiwalla Mody,Mark C Petrie,Ivo Petrov,Morten Schou,Michele Senni,David Sim,Peter van der Meer,Martin Lefkowitz,Yinong Zhou,Jianjian Gong,Eugene Braunwald,

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.
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.
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.
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.).

Copyright © 2021 Massachusetts Medical Society.

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Marc A Pfeffer

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.).

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 G Steg

Otavio Berwanger

Maja Cikes

Carmine G De Pasquale

Cara East

Alberto Fernandez

Karola Jering

Ulf Landmesser

Roxana Mehran

Béla Merkely

Freny Vaghaiwalla Mody

Mark C Petrie

Ivo Petrov

Morten Schou

Michele Senni

David Sim

Peter van der Meer

Martin Lefkowitz

Yinong Zhou

Jianjian Gong

Eugene Braunwald

References

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Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.

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About The Expert

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