Effects of ivabradine in patients with stable angina receiving β-blockers according to baseline heart rate: an analysis of the ASSOCIATE study

Background: Any increase in heart rate (HR) during daily activities above the ischemic threshold may trigger myocardial ischemia. HR reduction with the If inhibitor ivabradine has been demonstrated to confer anti-ischemic and antianginal efficacy in patients with stable angina pectoris. This analysis of the ASSOCIATE trial assessed whether the anti-ischemic efficacy and safety of ivabradine were comparable in patients with baseline resting HRs above and below the median.

Methods: Patients with chronic stable angina pectoris were randomized to treatment with ivabradine (5 to 7.5mg bid) or placebo for 4 months, in addition to atenolol 50mg od. The effect of treatment on exercise tolerance test parameters was analyzed in two groups according to baseline HR: > 65 bpm (n=418) versus ≤ 65 bpm (n=436) (above and below the median, respectively).

Results: Ivabradine reduced resting HR in both groups with placebo-corrected reductions of -9.1 (95% CI -11.0 to -7.3; >65 bpm group) and -5.9 (95% CI -7.5 to -4.3; ≤ 65 bpm group) (both P<0.001 versus placebo). Ivabradine reduced heart rate at all stages of exercise (all P<0.001). Improvements in exercise capacity (total exercise duration, time to limiting angina, angina onset, and 1-mm ST segment depression, all P<0.05) were recorded in both HR groups. There were no differences between the two groups in terms of safety.

Conclusions: Ivabradine resulted in significant improvements in exercise capacity relative to placebo in patients with stable angina pectoris receiving beta-blocker therapy whether their resting HR was above or below 65 bpm.