Spironolactone, a medication frequently prescribed for hypertension, may offer a protective effect against heart failure in individuals recovering from a heart attack, according to findings from the CLEAR SYNERGY trial (OASIS 9). The research, presented at the American Heart Association’s Scientific Sessions 2024 and simultaneously published in the New England Journal of Medicine, suggests that spironolactone reduces the risk of new or worsening heart failure, though it does not significantly impact mortality or other major cardiovascular events.
The CLEAR SYNERGY trial enrolled 7,062 adults across 14 countries who had experienced a severe heart attack. Participants were randomly assigned to one of four groups: spironolactone and colchicine, spironolactone and a placebo, colchicine and a placebo, or two placebos. The primary aim was to assess whether routine spironolactone use post-heart attack could broadly reduce the incidence of heart failure and death, irrespective of pre-existing heart failure.
Key Findings from CLEAR SYNERGY
The trial revealed that while overall rates of death from heart-related issues were similar between the spironolactone and placebo groups (3.2% vs. 3.3%, respectively), participants taking spironolactone experienced a 31% reduction in the risk of new or worsening heart failure (1.6% vs. 2.4%). However, the study also noted a higher incidence of elevated potassium levels in the spironolactone group (1.1% vs. 0.05%), leading to increased medication discontinuation.
Sanjit Jolly, M.D., M.Sc., the lead author of the trial and a scientist at the Population Health Research Institute, commented, “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.”
Trial Design and Patient Characteristics
The study enrolled participants between February 1, 2018, and November 8, 2022, with a median follow-up of three years. The average age of participants was 60, with 20% self-identifying as women. The majority (95%) had experienced a ST elevation myocardial infarction (STEMI), and approximately 18% had diabetes.
Limitations and Considerations
The researchers acknowledged several limitations, including the underrepresentation of women and diverse racial and ethnic groups, which may limit the generalizability of the findings. Additionally, the side effects of colchicine could have influenced participants' decisions to discontinue spironolactone, potentially affecting the study's statistical power, as evidenced by the higher-than-expected discontinuation rate of 28%.
Implications for Clinical Practice
These findings suggest that spironolactone may be a valuable addition to post-heart attack treatment regimens for reducing the risk of heart failure. However, healthcare providers should carefully monitor potassium levels in patients taking spironolactone to mitigate potential adverse effects. Further research is needed to explore the long-term impact of spironolactone on heart health and to determine its effectiveness in more diverse populations.
