- Question
- Does lowering heart rate with ivabradine reduce cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction?
- Design
- Randomized, double-blind, placebo-controlled, parallel-group trial enrolling 10917 patients at 781 centres in 33 countries. Median follow-up was 19 months.
- Population
- Patients with coronary artery disease and a left-ventricular ejection fraction below 40%. Mean baseline heart rate was 71.6 beats per minute and 87% were receiving beta blockers.
- Intervention
- Ivabradine 5 mg, with the intention of up-titrating to a target dose of 7.5 mg twice daily, on top of appropriate cardiovascular medication.
- Control
- Matched placebo on top of appropriate cardiovascular medication.
- Primary outcome
- Composite of cardiovascular death, hospital admission for acute myocardial infarction, and hospital admission for new-onset or worsening heart failure.
- Results
- Ivabradine did not affect the primary endpoint (HR 1.00; 95% CI 0.91-1.1; p=0.94), despite lowering heart rate by 6 bpm at 12 months versus placebo. In the prespecified subgroup with heart rate of 70 bpm or greater, the primary endpoint was also unchanged (HR 0.91; 95% CI 0.81-1.04; p=0.17), but admission to hospital for fatal and non-fatal myocardial infarction was reduced (HR 0.64; 95% CI 0.49-0.84; p=0.001).
- Safety
- No safety concerns were identified. Serious adverse events occurred in 1233 patients (22.5%) on ivabradine and 1239 (22.8%) on placebo (p=0.70).
- Conclusion
- Heart rate reduction with ivabradine did not improve cardiac outcomes across all patients with stable coronary artery disease and systolic dysfunction, although it may reduce coronary events in the subgroup with heart rate of 70 bpm or greater.
- Why it matters
- The trial showed that heart rate alone was not a useful therapeutic target across this whole population and generated the hypothesis of a coronary benefit in patients with elevated heart rate, which was explored in later studies.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 10, 2026