Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial

Aims BEAUTIFUL found no impact of ivabradine on outcomes in patients with stable coronary artery disease (CAD) and left ventricular systolic dysfunction (LVSD). We performed a post hoc analysis of the effect of ivabradine in BEAUTIFUL patients whose limiting symptom at baseline was angina, particularly in terms of coronary outcomes. Methods and results Of the BEAUTIFUL population, 13.8% had limiting angina at baseline (734 ivabradine, 773 placebo); of these, 712 patients had heart rate ≥70 b.p.m. Median duration of follow-up was 18 months. Ivabradine was associated with a 24% reduction in the primary endpoint (cardiovascular mortality or hospitalization for fatal and non-fatal myocardial infarction [MI] or heart failure) (HR, 0.76; 95% CI, 0.58–1.00) and a 42% reduction in hospitalization for MI (HR, 0.58, 95% CI, 0.37–0.92). In patients with heart rate ≥70 b.p.m., there was a 73% reduction in hospitalization for MI (HR, 0.27, 95% CI, 0.11–0.66) and a 59% reduction in coronary revascularization (HR, 0.41, 95% CI, 0.17–0.99). Ivabradine was safe and well tolerated. Conclusion Our analyses raises the possibility that ivabradine may be helpful to reduce major cardiovascular events in patients with stable CAD and LVSD who present with limiting angina. However, a large-scale clinical trial is ongoing, which will formally test this hypothesis.