Ivabradine Fails to Prevent Heart Injury After Non-Cardiac Surgery, major Trial Finds
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A new study presented at the European Society of Cardiology (ESC) Congress 2025 reveals that the medication ivabradine does not reduce the incidence of myocardial injury after non-cardiac surgery, challenging previous assumptions about heart rate management during procedures.
MINS: A Significant Post-Surgical risk
Myocardial injury after non-cardiac surgery (MINS) is a serious and surprisingly common complication, accounting for roughly 13% of all deaths within 30 days of undergoing surgery. Researchers have long theorized that elevated heart rates during surgery contribute to increased myocardial oxygen demand, perhaps leading to injury. While beta-blockers have been used to lower heart rate and mitigate this risk, they carry potential side effects like hypotension, death, and stroke.
The PREVENT-MINS trial aimed to determine if ivabradine – a medication already used to treat angina and heart failure that selectively slows heart rate – could offer a safer choice for preventing MINS in patients undergoing non-cardiac surgery, especially those with or at risk of atherosclerotic disease.
Trial Design and Early Termination
The double-blind, placebo-controlled, randomized PREVENT-MINS trial was conducted across 26 hospitals in Poland. A total of 2,101 patients aged 45 and older were enrolled, including individuals with established atherosclerotic disease (such as coronary artery disease, peripheral artery disease, or prior stroke) or significant risk factors like diabetes, hypertension, and age over 70. Participants were randomly assigned to receive either ivabradine (5 mg twice daily for up to 7 days, starting one hour before surgery) or a placebo.
However, the trial was halted early in March 2025 by an autonomous Data Monitoring Committee due to a lack of evidence demonstrating efficacy – a finding known as “futility.”
Key Findings: No Overall Benefit, Potential Harm in Specific Subgroup
Analysis of the 2,101 randomized participants – with a median age of 70 and nearly half being women (49.4%) – showed that MINS occurred in 17.0% of the ivabradine group compared to 15.1% in the placebo group. This difference was not statistically significant, with a relative risk (RR) of 1.12 and a 95% confidence interval (CI) of 0.92 to 1.37 (p=0.25).
Notably, a subgroup analysis revealed a concerning trend: ivabradine was associated with an increased risk of MINS among patients with a prior history of coronary artery disease (RR 1.49; 95% CI 1.03 to 2.16). This effect was not observed in patients without a history of coronary artery disease (RR 0.98; 95% CI 0.78 to 1.24).
Modest Heart Rate Reduction and Increased Bradycardia
While ivabradine did lower the average heart rate during surgery by 3.2 beats per minute compared to placebo, there was no significant difference in blood pressure between the two groups. However, clinically important bradycardia – a dangerously slow heart rate – was more common in the ivabradine group (RR 1.18; 95% CI 1.00 to 1.40).
“Heart-rate lowering was modest and the possible higher MINS incidence in patients with known coronary artery disease is contrary to our original hypothesis,” stated a led researcher involved in the study. “Further research is needed to establish a method to safely control the heart’s stress associated with noncardiac surgery.”
The findings underscore the complexity of managing cardiovascular risk during surgery and highlight the need for more targeted strategies to protect patients from MINS.
