RCT: Routine Spironolactone Post-MI Does Not Reduce Cardiovascular Events
20 Nov, 2024 | 18:03h | UTCBackground: Mineralocorticoid receptor antagonists (MRAs), such as spironolactone, have demonstrated mortality benefits in patients with heart failure following myocardial infarction (MI). However, the efficacy of routine spironolactone use in all patients post-MI, regardless of heart failure status, remains uncertain.
Objective: To evaluate whether routine administration of spironolactone reduces cardiovascular events in patients after MI who have undergone percutaneous coronary intervention (PCI).
Methods: In a multicenter, double-blind, placebo-controlled trial with a 2-by-2 factorial design, 7,062 patients with MI undergoing PCI were randomized to receive spironolactone (25 mg daily) or placebo, and colchicine or placebo. The two primary outcomes were: (1) a composite of death from cardiovascular causes or new or worsening heart failure, assessed as the total number of events; and (2) a composite of the first occurrence of MI, stroke, new or worsening heart failure, or death from cardiovascular causes. Median follow-up was 3 years.
Results: No significant differences were observed between the spironolactone and placebo groups in the primary outcomes. For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group versus 220 events (2.1 per 100 patient-years) in the placebo group (hazard ratio [HR] adjusted for competing risk, 0.91; 95% confidence interval [CI], 0.69–1.21; P=0.51). For the second primary outcome, events occurred in 280 patients (7.9%) in the spironolactone group and 294 patients (8.3%) in the placebo group (HR adjusted for competing risk, 0.96; 95% CI, 0.81–1.13; P=0.60). Serious adverse events were similar between groups.
Conclusions: Routine use of spironolactone after MI did not reduce cardiovascular mortality or new or worsening heart failure compared to placebo.
Implications for Practice: These findings suggest that routine prescription of spironolactone for all patients after MI may not be beneficial and should be reconsidered. Clinicians should carefully evaluate the indication for MRAs post-MI, particularly in patients without heart failure, and remain cautious about routine use without clear evidence of benefit.
Study Strengths and Limitations: Strengths of the study include its large sample size, multicenter international design, and long follow-up period, enhancing the generalizability of the findings. However, limitations include lower-than-expected event rates, potentially reducing statistical power to detect significant differences. The high rate of discontinuation of the trial regimen and underrepresentation of women and certain racial and ethnic groups may also limit the applicability of the results. Additionally, the possibility of a type II error due to reduced power cannot be excluded.
Future Research: Further studies are warranted to identify specific subgroups of patients who may benefit from spironolactone post-MI and to explore alternative therapies that effectively reduce cardiovascular events after MI.