Efficacy of Ivabradine in Combination with Beta-Blocker Versus Uptitration of Beta-Blocker in Patients with Stable Angina

Abstract

The antianginal and anti-ischemic efficacy of the selective I (f) inhibitor ivabradine is established in patients with stable angina in monotherapy and in combination with other antianginals, including beta-blocker. This pilot study compared the antianginal and anti-ischemic efficacy and hemodynamic profile of ivabradine plus 5mg bisoprolol versus those of 10mg bisoprolol in patients with stable angina. Twenty-nine patients with stable angina and moderate left ventricular systolic dysfunction already on bisoprolol 5mg od were randomized into 2 groups. Group 1 (n = 17) received ivabradine (5-7.5mg bid) in addition to bisoprolol 5mg od, while in group 2 (n = 12) bisoprolol was uptitrated first to 7.5mg and then 10mg od. Patients underwent a treadmill test, 6-minute walking test, and echocardiography at baseline and after 2months. Mean resting heart rate decreased in both groups, from 76.6 ± 4.6bpm to 59.3 ± 2.5bpm (P < 0.001) in group 1 and from 75.9 ± 3.0bpm to 60.5 ± 2.3bpm (P = 0.002) in group 2. The effect on resting heart rate did not differ significantly between the two groups. However, more patients became asymptomatic in group 1 than in group 2. Addition of ivabradine also improved exercise capacity, as shown by the results of the 6-minute walking and exercise tolerance tests, whereas in group 2 neither parameter was significantly affected. Chronotropic reserve significantly improved with ivabradine, but not with bisoprolol 10mg. These results suggest that combining ivabradine with low dose bisoprolol in stable angina patients produces additional antianginal and anti-ischemic benefits and improves chronotropic reserve.