American Heart Association, 17th Nov, 2024 – The CLEAR-SYNERGY (OASIS 9) (Population Health Research Institute; NCT03048825) trial investigated long-term treatment with spironolactone verses placebo and colchicine verses placebo following percutaneous coronary intervention (PCI) in patients with myocardial infarction (MI).
CLEAR-SYNERGY (OASIS 9) was a 2 x 2 factorial design trial which included a SYNERGY stent registry to assess major adverse cardiac events following PCI. There were 7,062 MI patients across 14 countries that were enrolled in the trial with 95% having experienced ST segment elevation MI. Patients were randomized into four treatment groups: 25 mg of spironolactone and 0.5 mg of colchicine, 25 mg of spironolactone and placebo, 0.5 mg of colchicine and placebo, or two placebos.
The primary outcome measure for colchicine was the first occurrence of the composite of cardiovascular death, recurrent MI, stroke, or unplanned ischemia-driven revascularization. The co-primary outcomes for spironolactone were the total composite of cardiovascular death or new or worsening heart failure, and the first occurrence of cardiovascular death, new or worsening heart failure, recurrent MI, or stroke. Major adverse cardiac events were also measured in all patient groups. The median duration of follow-up was three years.
New data presented by Dr Sanjit Jolly (McMaster University, Hamilton, CA) revealed that daily treatment with spironolactone slightly reduced the occurrence of the primary outcome with 183 events in the spironolactone group verses 220 events in the placebo group (p = 0.51). However, spironolactone failed to significantly reduce the number of cardiovascular deaths, with a 3.2% reduction compared to a 3.3% reduction in the placebo group (HR 0.98). Additionally, high potassium levels in patients taking spironolactone were seen compared to patients taking placebo (1.1% as opposed to 0.6%, p = 0.01). Although this was one factor influencing 28% of patients to discontinue spironolactone, the medication achieved its expected effect of decreasing the risk of new or worsening heart failure with a 31% lower risk than in the groups receiving colchicine and placebo or two placebos. In the colchicine group, a 9.1% rate of the composite primary outcome measures proved nonsignificant in comparison to the 9.3% rate in the placebo group after an average of three and a half years(p = 0.93).
Although spironolactone didn’t impact the rate of death, recurrent MI, stroke, or unplanned ischemia-driven revascularization, more research is needed to further support the finding that spironolactone decreased the risk of new or worsening heart failure by 31% in MI patients. However, the neutral outcomes on colchicine showed no clear reduction in cardiovascular events, revealing the medication to be an ineffective option following PCI for MI patients.
Resources:
Clinical Trials. Colchicine and Spironolactone in Patients with MI / SYNERGY Stent Registry (CLEAR SYNERGY). 2024. https://clinicaltrials.gov/study/NCT03048825 (accessed 4 December 2024).
Jolly SS, d’Entremont M, Pitt B, et al. Routine Spironolactone in Acute Myocardial Infarction. The New England Journal of Medicine 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2405923; DOI: 10.1056/NEJMoa2405923
American Heart Association. Spironolactone, a blood pressure medication, may help reduce risk of new heart failure. Chicago: American Heart Association, 17 November 2024. https://newsroom.heart.org/news/spironolactone-a-blood-pressure-medication-may-help-reduce-risk-of-new-heart-failure (accessed 4 December 2024).
Alasnag MA. The CLEAR SYNERGY (OASIS 9) Trial: A 2x2 factorial randomized controlled trial of colchicine versus placebo and spironolactone versus placebo in patients with myocardial infarction. PCR Online 18 November 2024. https://www.pcronline.com/News/Whats-new-on-PCRonline/2024/AHA/The-CLEAR-SYNERGY-OASIS-9-Trial-A-2x2-factorial-randomized-controlled-trial-of-colchicine-versus-placebo-and-spironolactone-versus-placebo-in-patients-with-myocardial-infarction (accessed 4 December 2024).