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Published on: May 28, 2019
Routine Spironolactone in Acute Myocardial Infarction
Sanjit S Jolly1,2, Marc-André d'Entremont1,2,3, Bertram Pitt4
1Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
Insights
Spironolactone did not significantly reduce cardiovascular death or heart failure in patients post-myocardial infarction. This study found no significant benefit for spironolactone in preventing major adverse cardiovascular events in this patient population.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Mineralocorticoid receptor antagonists (MRAs) are established treatments for reducing mortality in patients with heart failure post-myocardial infarction (MI).
- The routine use of spironolactone, an MRA, in the broader post-MI population without established heart failure remains uncertain.
Purpose of the Study:
- To investigate the efficacy of spironolactone in reducing cardiovascular mortality and heart failure events in patients following myocardial infarction.
- To assess the impact of spironolactone on a composite of major adverse cardiovascular events, including MI, stroke, heart failure, and cardiovascular death.
Main Methods:
- A multicenter, randomized, double-blind, placebo-controlled trial with a 2x2 factorial design was conducted.
- 7062 patients post-MI who underwent percutaneous coronary intervention were randomized to receive either spironolactone or placebo.
- Primary outcomes included a composite of cardiovascular death or new/worsening heart failure, and a composite of first occurrence of MI, stroke, new/worsening heart failure, or cardiovascular death.
Main Results:
- Spironolactone did not significantly reduce the first primary outcome (cardiovascular death or new/worsening heart failure) compared to placebo (HR 0.91, P=0.51).
- The second primary outcome (composite of cardiovascular death, MI, stroke, or new/worsening heart failure) was also not significantly reduced by spironolactone (HR 0.96, P=0.60).
- Serious adverse events were comparable between the spironolactone and placebo groups.
Conclusions:
- Routine use of spironolactone in patients after myocardial infarction did not lead to a significant reduction in cardiovascular death, heart failure, or other major adverse cardiovascular events.
- The findings suggest that spironolactone may not offer additional benefits in this specific patient population beyond established therapies.
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.).
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