Abstract Body (Do not enter title and authors here): Background: While mineralocorticoid antagonists (MRA) reduce mortality in patients developing heart failure post myocardial infarction (MI), it is unclear whether they are beneficial in an unselected post-MI population.

Aims: Using a systematic review and meta-analysis, we aim to determine the effect of MRA treatment versus no MRA treatment on all-cause mortality in unselected post-MI patients from randomized data, simultaneously with the presentation of the largest randomized controlled trial on the topic, the CLEAR SYNERGY trial.

Methods/Approach: We completed a systematic review of all randomized controlled trials comparing MRA treatment to no MRA treatment in post-MI patients. We will perform our primary analysis using fixed effects with the Peto odds ratio method and use random effects as a sensitivity analysis. The primary outcome will be all-cause mortality, and secondary outcomes will include cardiovascular mortality, new or worsening heart failure, recurrent myocardial infarction and stroke.

Results/Data: Our systematic review of Pubmed, Embase, and CENTRAL from inception until April 30, 2024, yielded 456 records. A total of 11,199 participants from 11 randomized clinical trials will be included in addition to the late-breaking CLEAR SYNERGY trial. The CLEAR SYNERGY trial is a 2 x 2 factorial randomized controlled trial of low-dose colchicine 0.5mg daily versus placebo and spironolactone 25mg daily versus placebo in 7,062 post-MI patients who were within 72h of the index percutaneous coronary intervention. The results of the spironolactone factorial will be presented in the fall of 2024 with an expected median follow-up of 3.5 years. As the investigators of the CLEAR SYNERGY trial, we will combine our data with the other 11 trials for a total of 12 trials and 18,261 participants.

Conclusions: CLEAR SYNERGY is the largest randomized controlled trial with the longest follow-up of spironolactone in the post-MI population. Our meta-analysis will provide updated effect estimates of post-MI MRA treatment, leveraging the late-breaking CLEAR SYNERGY data to reflect the totality of the evidence.