Ivabradine for prevention of myocardial injury after noncardiac surgery (PREVENT-MINS trial): study protocol for a randomized controlled trial.

BACKGROUND: Myocardial injury is a major cause of death after noncardiac surgery and is associated with long-term cardiovascular outcomes. Perioperative tachycardia increases this risk. Although perioperative beta blockers prevent myocardial injury, they increase the risk of death and stroke, which analyses suggest is due to a significant increase in hypotension. Ivabradine, a selective heart rate-lowering drug, may offer a safer alternative. The primary objective of the PREVENT-MINS trial is to determine whether perioperative administration of ivabradine is superior to placebo for the prevention of myocardial injury after noncardiac surgery (MINS) in patients with or at risk of atherosclerotic disease having noncardiac surgery.  METHODS: The PREVENT-MINS trial is a multicentre, parallel-group, blinded, placebo-controlled trial conducted in 26 hospitals in Poland. It will enroll 2500 patients aged ≥ 45 years undergoing noncardiac surgery with at least one risk factor for myocardial injury. Participants will be randomized in a 1:1 ratio to receive ivabradine 5 mg orally twice daily for 7 days starting 1 h before surgery or placebo. The primary outcome is MINS within 30 days after randomization; independent experts will adjudicate this outcome. Secondary outcomes include vascular complications, mortality, haemodynamics, and quality of life at 30 days. Additional tertiary and 1-year outcomes will assess long-term cardiovascular and surgical complications. Analyses will follow an intention-to-treat approach. For the primary outcome, a chi-squared test will be conducted, with results presented as unadjusted relative risk (RR) accompanied by 95% confidence intervals (CIs) and p-values.  DISCUSSION: This trial will generate high-quality, generalizable data due to its large population and rigorous design, including blinding. Moreover, it will be one of the first large-scale trials specifically focused on preventing MINS.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05279651. Registered on 4 March 2022.