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.).

B P Koirala Institute of Health Sciences Dharan Nepal

Cardiology Department University Hospital La Paz Madrid

Cardiology Division Heart Center Luzerner Kantonsspital and Faculty of Health Sciences and Medicine University of Lucerne Lucerne Switzerland

Caril and Edyth Lindner Center for Research and Education Christ Hospital Health Network Cincinnati

Centre Hospitalier Universitaire de Sherbrooke Sherbrooke QC Canada

Clinical Hospital Tetovo Tetovo North Macedonia

Department of Cardiology Peninsula Health Frankston VIC Australia

Department of Medicine University of Saskatchewan Moose Jaw Canada

Division of Clinical Medicine University of Sheffield Sheffield United Kingdom

Dutch Network for Cardiovascular Research Utrecht the Netherlands

Hamilton Health Sciences Hamilton ON Canada

Institut za Kardiovaskularne Bolesti Dedinje Belgrade Belgrade Serbia

London Health Sciences Centre University of Western Ontario London Canada

Medical Faculty University Clinic of Cardiology University Ss Cyril and Methodius Skopje North Macedonia

NIHR Sheffield Biomedical Research Centre Sheffield Teaching Hospitals NHS Foundation Trust Sheffield United Kingdom

Northwest Clinics Alkmaar the Netherlands

Peninsula Clinical School Central Clinical School Monash University Melbourne VIC Australia

Population Health Research Institute McMaster University Hamilton ON Canada

Quebec Heart Lung Institute Laval University Quebec QC Canada

Radboud University Medical Center Nijmegen the Netherlands

Sorbonne University ACTION Study Group Centre Hospitalier Universitaire Pitié Salpêtrière Assistance Publique Hôpitaux de Paris Paris

Southlake Regional Health Centre Newmarket University of Toronto Toronto

St Mary's Hospital Kitchener ON Canada

University Clinical Center of Serbia and Faculty of Medicine University of Belgrade Belgrade

University Hospital Brno Brno Czech Republic

University of British Columbia and Centre for Cardiovascular Innovation Vancouver Coastal Health Vancouver Canada

University of Michigan Ann Arbor

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ClinicalTrials.gov
NCT03048825