on February 3, 2003
Circulation. 2003
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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Submitted on August 5, 2002
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.). * To whom correspondence should be addressed. 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 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.
Accepted on October 30, 2002
Antianginal and Antiischemic Effects of Ivabradine, an If Inhibitor, in Stable Angina. A Randomized, Double-Blind, Multicentered, Placebo-Controlled Trial
Jeffrey S. Borer MD*,
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.
Key words: angina • coronary disease • ischemia
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