Efficacy and safety of ivabradine in Japanese patients with chronic heart failure ― J-SHIFT study ―

Abstract

Background: Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, an If inhibitor, improved outcomes in patients with HF and reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of <1 in the primary composite endpoint of cardiovascular death or hospital admission for worsening HF. Methods and Results: Patients with NYHA functional class II-IV, left ventricular EF ≤35%, and resting HR ≥75beats/min in sinus rhythm under optimal medical therapy received ivabradine (n=127) or placebo (n=127). Mean reduction in resting HR was significantly greater in the ivabradine group (15.2 vs. 6.1beats/min, P<0.0001). However, symptomatic bradycardia did not occur. A total of 26 (20.5%) patients in the ivabradine group and 37 (29.1%) patients in the placebo group had the primary endpoint event (hazard ratio 0.67, 95% CI 0.40-1.11, P=0.1179) during median follow-up of 589 days. Mild phosphenes were reported in 8 (6.3%) patients in the ivabradine group and 4 (3.1%) patients in the placebo group (P=0.3760). Conclusions: The J-SHIFT study supported the efficacy and safety of ivabradine for Japanese HFrEF patients, in accord with the SHIFT study.