Routine Spironolactone in Acute Myocardial Infarction

Sanjit S Jolly; Marc-André d'Entremont; Bertram Pitt; Shun Fu Lee; Rajibul Mian; Jessica Tyrwhitt; Sasko Kedev; Gilles Montalescot; Jan H Cornel; Goran Stanković; Raul Moreno; Robert F Storey; Timothy D Henry; Shamir R Mehta; Matthias Bossard; Petr Kala; Ravinay Bhindi; Biljana Zafirovska; P J Devereaux; John Eikelboom; John A Cairns; Madhu K Natarajan; J D Schwalm; Sanjib K Sharma; Wadea Tarhuni; David Conen; Sarah Tawadros; Shahar Lavi; Valon Asani; Dragan Topic; Warren J Cantor; Olivier F Bertrand; Ali Pourdjabbar; Salim Yusuf; CLEAR investigators

doi:10.1056/NEJMoa2405923

Routine Spironolactone in Acute Myocardial Infarction

N Engl J Med. 2024 Nov 17. doi: 10.1056/NEJMoa2405923. Online ahead of print.

Authors

Sanjit S Jolly¹, Marc-André d'Entremont¹, Bertram Pitt¹, Shun Fu Lee¹, Rajibul Mian¹, Jessica Tyrwhitt¹, Sasko Kedev¹, Gilles Montalescot¹, Jan H Cornel¹, Goran Stanković¹, Raul Moreno¹, Robert F Storey¹, Timothy D Henry¹, Shamir R Mehta¹, Matthias Bossard¹, Petr Kala¹, Ravinay Bhindi¹, Biljana Zafirovska¹, P J Devereaux¹, John Eikelboom¹, John A Cairns¹, Madhu K Natarajan¹, J D Schwalm¹, Sanjib K Sharma¹, Wadea Tarhuni¹, David Conen¹, Sarah Tawadros¹, Shahar Lavi¹, Valon Asani¹, Dragan Topic¹, Warren J Cantor¹, Olivier F Bertrand¹, Ali Pourdjabbar¹, Salim Yusuf¹; CLEAR investigators

Affiliation

¹ From the Population Health Research Institute, McMaster University (S.S.J., M.-A.E., S.F.L., R. Mian, J.T., S.R.M., P.J.D., J.E., M.K.N., J.D.S., D.C., S.T., S.Y.), and Hamilton Health Sciences (S.S.J., M.-A.E., S.F.L., R. Mian, S.R.M., P.J.D., J.E., M.K.N., J.D.S., D.C.), Hamilton, ON, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC (M.-A.E.), the University of British Columbia and Centre for Cardiovascular Innovation, Vancouver Coastal Health, Vancouver (J.A.C.), the Department of Medicine, University of Saskatchewan, Moose Jaw (W.T.), London Health Sciences Centre, University of Western Ontario, London (S.L.), Southlake Regional Health Centre, Newmarket, University of Toronto, Toronto (W.J.C.), Quebec Heart-Lung Institute, Laval University, Quebec, QC (O.F.B.), and St. Mary's Hospital, Kitchener, ON (A.P.) - all in Canada; the University of Michigan, Ann Arbor (B.P.); the Medical Faculty, University Clinic of Cardiology, University Ss. Cyril and Methodius, Skopje, North Macedonia (S.K., B.Z.); Sorbonne University, ACTION Study Group, Centre Hospitalier Universitaire Pitié-Salpêtrière Assistance Publique-Hôpitaux de Paris, Paris (G.M.); Dutch Network for Cardiovascular Research, Utrecht, Radboud University Medical Center, Nijmegen, and Northwest Clinics, Alkmaar - all in the Netherlands (J.H.C.); University Clinical Center of Serbia and the Faculty of Medicine, University of Belgrade (G.S.), and Institut za Kardiovaskularne Bolesti Dedinje-Belgrade (D.T.) - all in Belgrade; the Cardiology Department, University Hospital La Paz, Madrid (R. Moreno); NIHR Sheffield Biomedical Research Centre, Sheffield Teaching Hospitals NHS Foundation Trust, and the Division of Clinical Medicine, University of Sheffield, Sheffield - both in the United Kingdom (R.F.S.); the Caril and Edyth Lindner Center for Research and Education, Christ Hospital Health Network, Cincinnati (T.D.H.); the Cardiology Division, Heart Center, Luzerner Kantonsspital, and the Faculty of Health Sciences and Medicine, University of Lucerne, Lucerne, Switzerland (M.B.); University Hospital Brno, Brno, Czech Republic (P.K.); the Department of Cardiology, Peninsula Health, Frankston, VIC, and Peninsula Clinical School, Central Clinical School. Monash University, Melbourne, VIC - both in Australia (R.B.); B.P. Koirala Institute of Health Sciences, Dharan, Nepal (S.K.S.); and Clinical Hospital Tetovo, Tetovo, North Macedonia (V.A.).

PMID: 39555814
DOI: 10.1056/NEJMoa2405923

Abstract

Background: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.

Methods: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo. The results of the spironolactone trial are reported here. The two primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events; and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes. Safety was also assessed.

Results: We enrolled 7062 patients at 104 centers in 14 countries; 3537 patients were assigned to receive spironolactone and 3525 to receive placebo. At the time of our analyses, the vital status was unknown for 45 patients (0.6%). For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group as compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (hazard ratio adjusted for competing risk of death from noncardiovascular causes, 0.91; 95% confidence interval [CI], 0.69 to 1.21; P = 0.51). With respect to the second primary outcome, an event occurred in 280 of 3537 patients (7.9%) in the spironolactone group and 294 of 3525 patients (8.3%) in the placebo group (hazard ratio adjusted for competing risk, 0.96; 95% CI, 0.81 to 1.13; P = 0.60). Serious adverse events were reported in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group.

Conclusions: Among patients with myocardial infarction, spironolactone did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure or the incidence of a composite of death from cardiovascular causes, myocardial infarction, stroke, or new or worsening heart failure. (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).

Associated data

ClinicalTrials.gov/NCT03048825