CVD
Corey Diamond, PharmD
Spironolactone, a mineralocorticoid receptor antagonist, has been shown to improve outcomes in patients with heart failure, but its routine use following myocardial infarction remains uncertain. A recent study published on November 17, 2024, in NEJM investigated whether adding spironolactone to standard care after a heart attack could reduce cardiovascular mortality and heart failure–related complications.
The researchers found that, over a median follow up of 3 years, spironolactone had no significant reduction in cardiovascular deaths, recurrent heart attacks, strokes, or worsening heart failure.
Design
Jolly and colleagues conducted a large, international, multicenter, randomized, placebo-controlled trial designed to assess the potential benefits of routine spironolactone use in patients following myocardial infarction. The study simultaneously evaluated the effects of both spironolactone and colchicine, with patients randomly assigned to one of four groups: spironolactone and colchicine, spironolactone and placebo, colchicine and placebo, or double placebo. This summary focuses on the spironolactone component of the trial.
Eligible participants included patients who had experienced either ST-segment elevation myocardial infarction or large non-ST-segment elevation myocardial infarction and had undergone percutaneous coronary intervention. Additional inclusion factors for patients with myocardial infarction included left ventricular ejection fraction of 45% or lower, diabetes, multivessel coronary artery disease, prior myocardial infarction, or age over 60 years.
The primary efficacy endpoints were two composite outcomes: a composite of cardiovascular death plus new or worsening heart failure and a composite of cardiovascular death, recurrent myocardial infarction, stroke, or new or worsening heart failure. Secondary endpoints included additional cardiovascular complications, changes in kidney function, and safety concerns such as hyperkalemia.
Benefits and risks
The study found that spironolactone did not significantly improve outcomes for patients recovering from myocardial infarction. Over a median follow up of 3 years, there was no notable reduction in cardiovascular mortality, recurrent heart attacks, strokes, or worsening heart failure among those .who received spironolactone compared with those given a placebo.
The incidence of the primary composite outcome, cardiovascular death or worsening heart failure, was similar between the two groups, with no statistically meaningful difference in risk. Likewise, when broader cardiovascular events were analyzed, including stroke and recurrent myocardial infarction, spironolactone showed no clear benefit.
In terms of safety, spironolactone was associated with a higher likelihood of adverse effects. Patients receiving the drug experienced increased rates of hyperkalemia and gynecomastia compared to those on placebo, although there was no major difference in serious renal complications.
Implications
Overall, Jolly and colleagues’ findings show that in a population of patients who have experienced a myocardial infarction without heart failure, spironolactone does not provide a protective effect.
The results suggested that its routine use after a heart attack may not be necessary unless other indications, such as heart failure, are present. This is in contrast with previous studies that demonstrated benefits of mineralocorticoid receptor antagonists in patients with heart failure.
“We did not demonstrate a reduction in mortality with spironolactone. The point estimate for heart failure events in our trial was generally consistent with the findings of previous trials, which reported reductions in heart failure events with spironolactone,” the authors said. “The lack of an apparent reduction in cardiovascular mortality may relate to improvements in clinical care over the last 2 decades, which have resulted in overall lower mortality after myocardial infarction and a reduction in the power of trials to detect meaningful differences.”
The study had several limitations that may have influenced the findings. The overall incidence of cardiovascular events was lower than expected, reducing statistical power to detect smaller but potentially meaningful benefits of spironolactone. Also, a high rate of treatment discontinuation may have masked potential effects of spironolactone. The trial also lacked data on left ventricular ejection fraction, limiting subgroup analysis. Lastly, women and certain racial and ethnic groups were underrepresented, making generalizability uncertain. ■