Ivabradine in Patients Undergoing Noncardiac Surgery: a Randomized Controlled Trial

Background: Perioperative beta-blockade lowers heart rate and decreases the risk of myocardial infarction but increases the risk of hypotension, death, and stroke. Ivabradine, a selective heart rate–lowering agent, may prevent prognostically important myocardial injury after noncardiac surgery (MINS) without causing hemodynamic instability. Methods: In this multicenter, double-blind, placebo-controlled trial, we assigned patients aged ≥45 years with, or at risk of, atherosclerotic disease undergoing noncardiac surgery to receive ivabradine (5 mg orally twice daily for up to 7 days, starting 1 hour before surgery) or placebo. The primary outcome was MINS within 30 days from randomization. Results: All of 2101 participants who underwent randomization were included in the intention-to-treat population. MINS occurred in 178 of 1050 patients (17.0%) in the ivabradine group and in 159 of 1051 patients (15.1%) in the placebo group (relative risk [RR], 1.12; 95% confidence interval [CI], 0.92 to 1.37; p=0.25). Enrollment was halted at the prespecified interim analysis due to a conditional power of 6%, below the futility boundary of 20%. The intraoperative mean heart rate was lower in the ivabradine group by 3.2 beats per minute than in the placebo group (95% CI, -4.07 to -2.36), with no difference in intraoperative mean arterial pressure. Conclusions: Among patients undergoing noncardiac surgery, ivabradine did not reduce the occurrence of MINS.