Photo Credit: Ollaweila

Routine spironolactone after myocardial infarction (MI) did not reduce cardiovascular AEs in the CLEAR SYNERGY (OASIS 9) trial. However, the on-treatment analysis suggested that the study drug may benefit the population.

Prof. Sanjit Jolly, MsC, from McMaster University, in Canada, and colleagues evaluated whether routine spironolactone could reduce cardiovascular AEs among patients with ST-elevation MI (STEMI) or large non-STEMI. The international CLEAR SYNERGY trial (NCT03048825) with a 2×2 factorial design randomly assigned 7,602 patients who underwent percutaneous coronary intervention (PCI) 1:1 to 25 mg daily spironolactone or placebo within 72 hours of the procedure^1,2. Both groups were then randomly assigned to receive colchicine or placebo.

The primary endpoints were a composite of cardiovascular death, or new or worsening heart failure, evaluated as the total number of events, and a composite of the first occurrence of cardiovascular death, MI, stroke, or new or worsening heart failure. Prof. Jolly presented the results of the spironolactone and matching placebo groups².

After 403 events, no significant differences were seen between the study arms in the first primary endpoint (HR 0.89; 95% CI 0.73–1.08; P=0.23). The authors did see a trend toward a reduction in new or worsening heart failure in the spironolactone arm compared with the placebo arm (1.6% vs 2.4%; HR 0.69; 95% CI 0.49–0.96). “Since the primary endpoint was not met, this is only explorative information,” clarified Prof. Jolly.

The on-treatment analysis displayed a treatment effect on the first (1.5% vs 2.0%; HR 0.79; 95% CI 0.63–1.00; P=0.047) and second primary endpoint (5.8% vs 7.2%; HR 0.83; 95% CI 0.69–1.00; P=0.046). Prof. Jolly mentioned that although the serious AE rates were comparable (7.2% vs 6.8%), they observed higher rates of hyperkalemia leading to study drug continuation (1.1% vs 0.05%; P=0.01) and gynecomastia (2.3% vs 0.5%; P<0.001) in the experimental arm.

“Post-MI outcomes have improved remarkably over the last 20 years, which may explain why it is so difficult to show the effect of an additional drug in this population,” argued Prof. Jolly at the end of his presentation.

Medical writing support was provided by Robert van den Heuvel.
Copyright ©2024 Medicom Medical Publishers