Safety of Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Systolic Dysfunction (from the BEAUTIFUL Hotter Substudy)

The BEAUTIFUL Holter substudy explored the cardiac safety of the If inhibitor ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction receiving optimal background therapy. The Holter substudy included 840 patients (ivabradine 5 or 7.5 mg/day, n = 421; placebo, n = 419), and the safety set consisted of 807 patients (ivabradine, n = 408; placebo, n = 399). Ambulatory 24-hour electrocardiographic Holter monitoring was performed at baseline and after 1 month and 6 months. There were no relevant between-group differences in baseline characteristics; 93% were receiving concomitant 13 blocker. Treatment with ivabradine was associated with a decrease in 24-hour heart rate of 6.3 +/- 9.5 beats/min at last assessment versus no change with placebo (0.4 +/- 7.2 beats/min, p < 0.001, between-group difference), with a greater decrease in waking heart rate with ivabradine than during sleep (6.8 +/- 10.4 vs 5.2 +/- 8.9 beats/min, respectively, at last visit). Incidence of episodes of heart rate < 30 beats/min during waking hours or during sleep was <= 1% in the 2 groups. Although there were more patients with heart rates < 40 or < 50 beats/min with ivabradine than with placebo (awake 12% vs 4% for < 40 beats/min and 68% vs 36% for < 50 beats/min, respectively; asleep 22% vs 5% for < 40 beats/min and 77% vs 50% for < 50 beats/min, respectively), there was no between-group difference in episode severity. There was no increase in incidence of conduction and rhythm disturbances. In conclusion, our results confirm that ivabradine significantly lowers heart rate without raising concern for cardiac safety. Our observations strongly support the safety of combining ivabradine with 13 blockers in patients with coronary artery disease. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:805-811)