title: Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial.
abstract: 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.
  
  
  RESULTS
  In a double-blind, placebo-controlled trial, 360 patients with a > or =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.
authors.affiliation: Weill Medical College of Cornell University, New York, NY, USA. CanadaD45@aol.com
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Borer
authors.forename: Kim
authors.initials: K
authors.lastname: Fox
authors.forename: Patrice
authors.initials: P
authors.lastname: Jaillon
authors.forename: Guy
authors.initials: G
authors.lastname: Lerebours
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy*; D012849:Sinoatrial Node / Q000187:drug effects; D016896:Treatment Outcome; D014786:Vision Disorders / Q000139:chemically induced
chemical_list: D001552:Benzazepines; D000077550:Ivabradine