Study title: Ivabradine in Patients Undergoing Noncardiac Surgery: a Randomized Controlled Trial

Published at: ESC Congress 2025

Link: https://esc365.escardio.org/presentation/312182

Prepared by: Dr. Simay Erdal Sayın

Background:
Myocardial injury after noncardiac surgery (MINS) is a frequently encountered complication associated with both short-term and long-term morbidity and mortality. Tachycardia observed during the perioperative period is considered one of the mechanisms of myocardial injury as it can increase myocardial oxygen consumption and lead to supply-demand imbalance. Although beta-blockers reduce the risk of myocardial infarction by decreasing heart rate, they also increase the risk of hypotension, stroke, and mortality. Ivabradine, in contrast to beta-blockers, reduces heart rate without affecting blood pressure. The property of ivabradine as a rate-lowering agent without causing hypotension suggests it may reduce myocardial injury that can occur during the perioperative period.

Objective:
To investigate whether ivabradine reduces the 30-day incidence of MINS in patients with atherosclerotic disease or risk factors undergoing noncardiac surgery.

Methods:
A multicenter, double-blind, placebo-controlled randomized superiority trial conducted at 26 hospitals in Poland. A total of 2101 patients aged ≥ 45 years undergoing noncardiac surgery with atherosclerotic disease or significant risk factors were randomized. Ivabradine 5 mg twice daily (n=1050) or placebo (n=1051) was administered starting 1 hour before surgery for up to 7 days. Troponin monitoring was performed before surgery and during the first three postoperative days. Electrocardiograms were obtained from patients with elevated troponin levels. Patients were followed for 30 days after randomization. Patients were divided into four subgroups: with and without coronary artery disease, with and without positive preoperative troponin levels, with and without intrathoracic surgery, and with heart rate above and below 75 beats per minute.

Results:
MINS developed in 17% of patients in the ivabradine group and 15.1% in the placebo group. 96.5% of MINS events occurred within the first 3 days after surgery. The mean age of patients was 70 years, with a preoperative mean heart rate of 75 beats per minute. The intraoperative mean heart rate was 3.2 beats per minute lower in the ivabradine group. There was no difference in intraoperative mean arterial pressure. Intraoperative tachycardia was less frequent in the ivabradine group compared to placebo. Clinically significant bradycardia was more common in the ivabradine group. Similar differences were recorded at 12 hours postoperatively. Vascular death or non-fatal MINS, stroke, or cardiac arrest occurred in 18.3% of the ivabradine group and 15.8% of the placebo group. In patients with coronary artery disease, the relative risk for myocardial injury was 1.49, while the relative risk for vascular events was 1.55.

Conclusions:
The use of ivabradine in noncardiac surgery did not reduce the risk of myocardial injury.

Commentary:
This study tested an important hypothesis regarding myocardial protection during the perioperative period. Similar studies on this topic have focused on the potential effectiveness of beta-blockers in myocardial protection by reducing myocardial oxygen consumption through heart rate reduction, and it was anticipated that ivabradine might also be effective in reducing myocardial injury due to its rate-lowering properties. Additionally, although the fact that ivabradine does not cause hypotension, unlike beta-blockers, strengthened this hypothesis, this study and previous similar studies have failed to demonstrate a significant effect of ivabradine in preventing myocardial injury. Furthermore, in the coronary artery disease group, where the greatest benefit and protection was expected, approximately 50% higher myocardial injury risk was demonstrated compared to placebo, and some previous similar studies support this result. In this study, patients received fixed doses, and the potential effect on myocardial injury prevention could be investigated if dose titration according to heart rate were performed.