title: Effects of ivabradine in patients with stable angina receiving β-blockers according to baseline heart rate: an analysis of the ASSOCIATE study.
abstract: BACKGROUND
  Any increase in heart rate (HR) during daily activities above the ischemic threshold may trigger myocardial ischemia. HR reduction with the If inhibitor ivabradine has been demonstrated to confer anti-ischemic and antianginal efficacy in patients with stable angina pectoris. This analysis of the ASSOCIATE trial assessed whether the anti-ischemic efficacy and safety of ivabradine were comparable in patients with baseline resting HRs above and below the median.
  
  
  METHODS
  Patients with chronic stable angina pectoris were randomized to treatment with ivabradine (5 to 7.5mg bid) or placebo for 4 months, in addition to atenolol 50mg od. The effect of treatment on exercise tolerance test parameters was analyzed in two groups according to baseline HR: > 65 bpm (n=418) versus ≤ 65 bpm (n=436) (above and below the median, respectively).
  
  
  RESULTS
  Ivabradine reduced resting HR in both groups with placebo-corrected reductions of -9.1 (95% CI -11.0 to -7.3; >65 bpm group) and -5.9 (95% CI -7.5 to -4.3; ≤ 65 bpm group) (both P<0.001 versus placebo). Ivabradine reduced heart rate at all stages of exercise (all P<0.001). Improvements in exercise capacity (total exercise duration, time to limiting angina, angina onset, and 1-mm ST segment depression, all P<0.05) were recorded in both HR groups. There were no differences between the two groups in terms of safety.
  
  
  CONCLUSIONS
  Ivabradine resulted in significant improvements in exercise capacity relative to placebo in patients with stable angina pectoris receiving beta-blocker therapy whether their resting HR was above or below 65 bpm.
authors.affiliation: Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada. Electronic address: jean-claude.tardif@icm-mhi.org.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.forename: Thomas
authors.initials: T
authors.lastname: Kahan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D060050:Angina, Stable / Q000188:drug therapy* / Q000503:physiopathology*; D001262:Atenolol / Q000008:administration & dosage; D001552:Benzazepines / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D000077550:Ivabradine; D001262:Atenolol
keywords: Beta-blocker; Heart rate; Ivabradine; Stable angina pectoris