November 17, 2024Open Access
Routine Spironolactone in Acute Myocardial Infarction
Key Result
Routine spironolactone did not significantly reduce the composite of cardiovascular death, myocardial infarction, stroke, or new or worsening heart failure compared to placebo in patients with acute myocardial infarction.
Study Design
Type
RCT (n=7,062)
Blinding
Double-blind
Randomization
Permuted block randomization
Multicenter
Yes
Structured PICO
Does routine spironolactone reduce cardiovascular death or new or worsening heart failure in patients with acute myocardial infarction who have undergone PCI?
P
Population
7,062 patients with acute myocardial infarction (95% STEMI, 5% NSTEMI) who had undergone percutaneous coronary intervention (PCI), mean age 61, 20.4% female, multinational (14 countries). Key inclusion: STEMI or large NSTEMI with PCI plus one or more risk criteria (left ventricular ejection fraction ≤45%, diabetes mellitus, multivessel coronary artery disease, prior myocardial infarction, or age >60 years).
I
Intervention
Spironolactone 25 mg tablets once daily added to standard post-myocardial infarction therapy.
C
Comparator
Matching placebo tablets once daily added to standard post-myocardial infarction therapy.
O
Outcome
Two co-primary outcomes: 1) Total events of cardiovascular death or new or worsening heart failure; 2) Time-to-first occurrence of the composite of cardiovascular death, myocardial infarction, stroke, or new or worsening heart failure, evaluated over a median follow-up of 3 years.composite
Routine administration of spironolactone in patients with acute myocardial infarction undergoing PCI does not significantly reduce the incidence of cardiovascular death or heart failure events.
Main Result
Effect estimate: HR 0.95 (95% CI 0.80-1.12)
Absolute Event Rate: 7.9% vs 8.3%
p-value: p=0.52
Limitations
- Information about left ventricular ejection fraction (LVEF) was not collected, preventing subgroup analyses based on LVEF.
- High rate of study drug discontinuation (28.0% in the spironolactone group and 24.4% in the placebo group).
- Lower-than-expected event rates required an increase in sample size and partitioning of the type 1 error rate.
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.).