Effect of ivabradine in patients with left-ventricular systolic dysfunction: a pooled analysis of individual patient data from the BEAUTIFUL and SHIFT trials.

Abstract

To test the effect of ivabradine on the outcomes in a broad population with left-ventricular (LV) systolic dysfunction with coronary artery disease (CAD) and/or heart failure (HF). Individual trial data from BEAUTIFUL and SHIFT were pooled to evaluate the effect of ivabradine on the outcomes in patients with LV dysfunction and heart rate ≥ 70 b.p.m. The pooled population (n = 11 897; baseline age 62.3 ± 10.4 years, heart rate 79.6 ± 9.2 b.p.m., and LV ejection fraction 30.3 ± 5.6%) was well treated according to current recommendations (87% beta-blockers, 90% renin-angiotensin system inhibitors). Median follow-up was 21 months. Treatment with ivabradine was associated with a 13% relative risk reduction for the composite of cardiovascular mortality or HF hospitalization (P < 0.001 vs. placebo); this was driven by HF hospitalizations (19%, P < 0.001). There were also significant relative risk reductions for the composite of cardiovascular mortality, HF hospitalizations, or myocardial infarction (MI) hospitalization (15%, P < 0.001); cardiovascular mortality and non-fatal MI (10%, P = 0.023); and MI hospitalization (23%, P = 0.009). Similar results were found in patients with differing clinical profiles. Ivabradine was well tolerated. Ivabradine may be important for the improvement of clinical outcomes in patients with LV systolic dysfunction and heart rate ≥ 70 b.p.m., whatever the primary clinical presentation (CAD or HF) or clinical status (NYHA class).