New insights into coronary artery disease: Role of ivabradine

Abstract

Ivabradine is a potent anti-anginal agent which works by specifically lowering heart rate but is devoid of hemodynamic actions. Its efficacy on ischaemia measured during exercise treadmill testing was comparable to that of atenolol in the randomized INITIATIVE trial. Recently, the combination of ivabradine with beta-blockers was tested in the randomized ASSOCIATE trial, which showed that ivabradine 7.5 mg bid produces additional effects to atenolol 50 mg qd on all indices of exercise performance, without untoward effects. Its effect on clinical outcomes has been tested in patients with coronary artery disease and left ventricular dysfunction in a large morbidity/mortality trial, the BEAUTIFUL trial. Ivabradine failed to affect the primary composite endpoint of cardiovascular death, myocardial infarction, and heart failure. However, among patients with baseline heart rate above 70 bpm, it did reduce coronary events, particularly the risk of myocardial infarction. In a recent post hoc analysis focusing on the 13.8 of patients with limiting angina, ivabradine reduced the primary endpoint by 24 and myocardial infarction by 42. In all trials, ivabradine was remarkably well tolerated. Overall, ivabradine is a potent anti-anginal agent, which can be used alone (when beta-blockers are contra-indicated or not tolerated) or in combination with beta-blockers, with excellent tolerability. In addition to its effects on ischaemia and anginal symptoms, ivabradine appears to improve clinical outcomes in patients with limiting angina or in patients with a heart rate above 70 bpm. This will be confirmed in the upcoming SIGNIFY randomized trial. © 2010 Published on behalf of the European Society of Cardiology.