Ivabradine in the management of coronary artery disease with or without left ventricular dysfunction or heart failure

Abstract

Heart rate reduction is an integral part of antianginal therapy. In this article, we examine currently available data related to the use of ivabradine in patients with angina pectoris with and without left ventricular dysfunction (LVD) or heart failure (HF). We explore results from large morbidity-mortality trials of ivabradine in stable coronary artery disease (CAD) without HF (SIGNIfY), stable CAD with LVD (BEAUTIfUL), and systolic HF (SHIfT). While ivabradine did not improve outcomes in the main population in SIGNIfY, analyses of the antianginal effect of ivabradine in a pre-specified angina subgroup (n = 12 049) were in line with knowledge of the antianginal properties of ivabradine, with improvements in angina class vs. placebo (P = 0.01) and a trend towards less elective coronary revascularization (P = 0.058). A post hoc analysis in a subgroup of 1507 BEAUTIfUL patients with limiting angina at baseline showed that risk reduction in favour of ivabradine, which was nominally statistically significant for hospitalization for myocardial infarction; the results were even better in patients with heart rate ≥70 b.p.m. Similarly, a post hoc analysis in 2220 SHIfT patients with angina at baseline indicated that the beneficial prognostic effects of ivabradine were maintained. The main differences between the three studies are LVD and ivabradine dosage (which was higher in SIGNIfY than in the other two trials). We conclude that heart rate reduction has a different role according to LVD. Provided that it is used at the recommended dose, ivabradine has been proved to be an effective, useful antianginal agent in patients with and without LVD.