Ivabradine in Patients Undergoing Noncardiac Surgery: A Randomized Controlled Trial

Circulation. 2025 Oct 21;152(16):1126-1135. doi: 10.1161/CIRCULATIONAHA.125.076704. Epub 2025 Aug 30.

Abstract

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 ≥45 years of age 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 the 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, 1.12 [95% CI, 0.92 to 1.37]; P=0.25). Enrollment was halted at the prespecified interim analysis because of 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.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05279651.

Keywords: ivabradine; myocardial injury after noncardiac surgery; perioperative care; troponin.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Cardiovascular Agents* / adverse effects
  • Cardiovascular Agents* / therapeutic use
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects
  • Humans
  • Ivabradine* / administration & dosage
  • Ivabradine* / adverse effects
  • Ivabradine* / therapeutic use
  • Male
  • Middle Aged
  • Postoperative Complications* / prevention & control
  • Surgical Procedures, Operative* / adverse effects
  • Treatment Outcome

Substances

  • Ivabradine
  • Cardiovascular Agents

Associated data

  • ClinicalTrials.gov/NCT05279651