Circulation. 2003;107:817-823
Published online before print February 3, 2003, doi: 10.1161/01.CIR.0000048143.25023.87
Published online before print February 3, 2003, doi: 10.1161/01.CIR.0000048143.25023.87
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(Circulation. 2003;107:817.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Antianginal and Antiischemic Effects of Ivabradine, an If Inhibitor, in Stable Angina
A Randomized, Double-Blind, Multicentered, Placebo-Controlled Trial
From Weill Medical College of Cornell University, New York, NY (J.S.B.); Royal Brompton Hospital, London, UK (K.F.); Saint-Antoine Paris 6 University Hospital, Assistance Publique-Hôpitaux de Paris, France (P.J.); and Institut de Recherches Internationales Servier, Courbevoie, France (G.L.).
Correspondence to Jeffrey S. Borer, MD, 47 East 88th St, New York, NY 10128-1152. E-mail CanadaD45{at}aol.com
Background— Heart rate reduction should benefit patients with chronic stable angina by improving myocardial perfusion and reducing myocardial oxygen demand. This study evaluated the antianginal and antiischemic effects of ivabradine, a new heart rate–lowering agent that acts specifically on the sinoatrial node.
Methods and Results— In a double-blind, placebo-controlled trial, 360 patients with a 
3-month history of chronic stable angina were randomly assigned to receive ivabradine (2.5, 5, or 10 mg BID) or placebo for 2 weeks, followed by an open-label 2- or 3-month extension on ivabradine (10 mg BID) and a 1-week randomized withdrawal to ivabradine (10 mg BID) or placebo. Primary efficacy criteria were changes in time to 1-mm ST-segment depression and time to limiting angina during bicycle exercise (exercise tolerance tests), performed at trough of drug activity. In the per-protocol population (n=257), time to 1-mm ST-segment depression increased in the 5 and 10 mg BID groups (P<0.005); time to limiting angina increased in the 10 mg BID group (P<0.05). Deterioration in all exercise tolerance test parameters occurred in patients who received placebo during randomized withdrawal (all P<0.02) but not in those still receiving ivabradine. No rebound phenomena were observed on treatment cessation.
Conclusions— Ivabradine produces dose-dependent improvements in exercise tolerance and time to development of ischemia during exercise. These results suggest that ivabradine, representing a novel class of antianginal drugs, is effective and safe during 3 months of use; longer-term safety requires additional assessment.
Key Words: angina • coronary disease • ischemia
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