Routine use of the blood pressure medication spironolactone among patients who have undergone percutaneous coronary intervention following acute myocardial infarction (MI) may reduce heart failure, but is not likely to reduce mortality, recurrent MI or stroke.
These are among the latest findings of the CLEAR SYNERGY (OASIS 9) trial, presented by Sanjit S Jolly (McMaster University and Hamilton Health Sciences, Hamilton, Canada) at the American Heart Association (AHA) 2024 Scientific Session (16–18 November, Chicago, USA) and published simultaneously in The New England Journal of Medicine.
CLEAR SYNERGY was a randomised, double-blind, 2×2 factorial design, placebo-controlled clinical trial, which randomised 7,062 patients between February 2018 and November 2022 into four groups receiving either spironolactone and the anti-inflammatory medicine colchicine; spironolactone and a placebo; colchicine and a placebo; or two placebos.
Patients were aged an average of 60 years old, and 20% were women. Among them, 95% had ST elevation myocardial infarction (STEMI), and 18% had diabetes type 1 or 2 diabetes.
Jolly presented findings from the analysis of the effect of colchicine within the trial at TCT 2024 (27–30 October, Washington, DC, USA), where he reported that the use of the medication after acute MI did not reduce cardiovascular death, MI, stroke or ischaemia-driven revascularisation compared to placebo.
Spironolactone is a mineralocorticoid receptor antagonist medication that blocks certain hormones. The trial’s focus was to determine whether the routine use of spironolactone after acute MI — regardless of whether the person had heart failure — could provide broader benefits in reducing the incidence of heart failure and death.
Reporting on the spironolactone arm of the trial at AHA 2024, Jolly detailed that 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), and that participants taking spironolactone (with or without colchicine) had a 31% lower risk of new or worsening heart failure than people taking colchicine with placebo or two placebos (1.6% vs. 2.4%, respectively).
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.
“While spironolactone didn’t reduce deaths or other major heart complications after a heart attack, it did reduce the likelihood of heart failure, which is an important finding for patients and health care professionals,” said Jolly. “Participants fared much better in this trial than in previous ones. This reflects the advances in angioplasty techniques in the overall care for heart attacks. Modern treatment approaches, including medication, stent technology and more timely interventions, have positively impacted patient outcomes.”
The research group highlighted several key study limitations, noting that women and people of different races and ethnicities were underrepresented in the participant pool, therefore making it difficult to generalise the results to the larger population.
The side effects of colchicine could have influenced a participant’s decision to stop taking spironolactone, they note, which may partly explain the higher-than-expected rate (28%) of people who discontinued using spironolactone and likely reduced the study’s statistical power.
