Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.

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.).

• 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 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, PARADISE-MI Investigators and Committees
• Journal: The New England journal of medicine (N Engl J Med) Vol. 385 Issue 20 Pg. 1845-1855 (11 11 2021) ISSN: 1533-4406 [Electronic] United States
• PMID: 34758252 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Massachusetts Medical Society.

Chemical References

• Aminobutyrates
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Biphenyl Compounds
• Drug Combinations
• Valsartan
• Ramipril
• sacubitril and valsartan sodium hydrate drug combination

Topics

• Aged
• Aminobutyrates (adverse effects, therapeutic use)
• Angiotensin Receptor Antagonists (adverse effects, therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (adverse effects, therapeutic use)
• Biphenyl Compounds (adverse effects, therapeutic use)
• Cardiovascular Diseases (mortality)
• Double-Blind Method
• Drug Combinations
• Female
• Heart Failure (prevention & control)
• Hospitalization (statistics & numerical data)
• Humans
• Hypotension (chemically induced)
• Male
• Middle Aged
• Myocardial Infarction (complications, drug therapy, mortality)
• Proportional Hazards Models
• Ramipril (adverse effects, therapeutic use)
• Stroke Volume
• Valsartan (adverse effects, therapeutic use)
• Ventricular Dysfunction, Left (etiology)