No benefit from ivabradine

Myocardial damage occurs in nearly 14% of patients undergoing high-risk non-cardiac surgery.^3,4 The most important modifiable risk factors include perioperative tachycardia and drops in blood pressure, which lead to increased myocardial oxygen consumption and damage. Although perioperative administration of beta-blockers can effectively reduce heart rate, symptomatic bradycardia and hypotension are associated with increased perioperative mortality. For this reason, routine beta-blocker therapy prior to non-cardiac surgery is not recommended in the ESC guidelines (class I, LOE A).³ Ivabradine is used to control heart rate in patients with coronary heart disease (CHD) and heart failure. Its advantage lies in reducing heart rate without simultaneously lowering blood pressure.

The PREVENT-MINS study investigated the effect of perioperative ivabradine administration on the incidence of perioperative myocardial injury (MINS). The study included 2,101 patients with atherosclerotic diseases (e.g., CHD, PAD, or previous stroke) or a high cardiovascular risk profile (e.g., diabetes mellitus, arterial hypertension, age ≥70 years). Patients were randomized 1:1 in 26 Polish clinics and received either ivabradine (5 mg orally twice daily, starting 1 hour before and continuing for up to 7 days after the procedure) or placebo. The primary endpoint was the 30-day incidence of MINS.

The study was terminated prematurely in March 2025 on the recommendation of the independent Data Monitoring Committee due to futility following a planned interim analysis.

The mean age of the patients was 70 years, 50% were women, and approximately 80% underwent high-risk procedures. In accordance with guidelines, highly sensitive troponin was measured in all patients before and 3 days after the procedure. The 30-day incidence of MINS was 17.0% in the ivabradine group and 15.1% in the placebo group (RR 1.12; 95% CI [0.92; 1.37]; p=0.25). In a subgroup analysis, ivabradine was associated with an increased risk of MINS in patients with CHD (RR 1.49; 95% CI [1.03; 2.16]; p_interaction=0.056). Intraoperative heart rate was lower in the ivabradine group than in the placebo group, while there was no difference in blood pressure. Clinically relevant bradycardia occurred more frequently with ivabradine (RR 1.18; 95% CI [1.00;1.40]). 

The authors concluded that treatment with ivabradine (5 mg orally, twice daily, for 30 days) did not reduce the risk of perioperative myocardial injury. 

The results of the PREVENT-MINS study are consistent with the existing evidence. In patients with cardiogenic or septic shock, ivabradine reduces heart rate without affecting the cardiac index.⁵ In patients with heart failure, no effect on long-term cardiovascular mortality, quality of life, or rehospitalization rates could be demonstrated.⁶

The increased MINS risk observed in the subgroup of CHD patients taking ivabradine remains difficult to explain. In patients with CHD and/or heart failure, earlier studies showed an increased incidence of atrial fibrillation with ivabradine, regardless of left ventricular function or dosage.⁷ However, in the PREVENT-MINS study, the incidence of new-onset atrial fibrillation was very low and identical between treatment groups, so this cannot explain the observation.

The PREVENT-MINS study is the largest study in this field to date and is expected to have a significant influence on future guidelines for the management of cardiac patients undergoing non-cardiac surgery.

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