New findings from CLEAR SYNERGY (OASIS 9) comparing spironolactone vs. placebo in patients with myocardial infarction (MI) found that the mineralocorticoid receptor antagonist did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure (HF) or the incidence of a composite of death from cardiovascular causes, MI, stroke, or new or worsening HF.

The spironolactone arm of the trial, which was presented at AHA 2024 and simultaneously published in NEJM, assessed data from the 3,537 patients who were assigned to receive spironolactone compared with the 3,525 assigned to receive placebo. The first primary outcome was a composite of death from cardiovascular causes or new or worsening HF. The second primary outcome consisted of a composite of the first occurrence of MI, stroke, new or worsening HF, or death from cardiovascular causes.

According to researchers, participants taking spironolactone (with or without colchicine) had a 31% lower risk of new or worsening HF than people taking colchicine with placebo or two placebos (1.6% vs. 2.4%, respectively). The overall rates of death from heart-related issues were similar between the spironolactone groups and the placebo groups (3.2% vs. 3.3%, respectively). Serious adverse events were also similar, occurring in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group.

"While spironolactone didn't reduce deaths or other major heart complications after a heart attack, it did reduce the likelihood of HF, which is an important finding for patients and health care professionals," said Sanjit Jolly, MD, MSc, lead author of the trial. He added that "participants fared much better in this trial than in previous ones," reflecting advances in angioplasty techniques and modern treatment approaches, including medication, stent technology and more timely interventions.

In other findings, researchers did observe that high potassium levels occurred at twice the rate within the spironolactone group compared to the placebo group (1.1% vs. 0.05%, respectively), leading to more participants discontinuing medication use.

In addition to the spironolactone findings, results from the colchicine arm of the trial showing no reductions in the incidence of the composite primary outcome of death from cardiovascular causes, recurrent MI, stroke, or unplanned ischemia-driven coronary revascularization were also published in NEJM.

According to Jolly and colleagues, a primary-outcome event occurred in 322 (9.1%) of the 3,528 patients assigned to receive colchicine and 327 (9.3%) of the 3,534 patients assigned to receive placebo over a median follow-up period of 3 years. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at three months, adjusted according to the baseline values, was −1.28 mg per liter. In other findings, a greater incidence of diarrhea was reported among patients in the colchicine group compared with those in the placebo group (10.2% vs. 6.6%), but the incidence of serious infections was similar between the two groups.