Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial

Eur Heart J. 2009 Oct;30(19):2337-45. doi: 10.1093/eurheartj/ehp358. Epub 2009 Aug 31.

Abstract

Aims: BEAUTIFUL found no impact of ivabradine on outcomes in patients with stable coronary artery disease (CAD) and left ventricular systolic dysfunction (LVSD). We performed a post hoc analysis of the effect of ivabradine in BEAUTIFUL patients whose limiting symptom at baseline was angina, particularly in terms of coronary outcomes.

Methods and results: Of the BEAUTIFUL population, 13.8% had limiting angina at baseline (734 ivabradine, 773 placebo); of these, 712 patients had heart rate > or =70 b.p.m. Median duration of follow-up was 18 months. Ivabradine was associated with a 24% reduction in the primary endpoint (cardiovascular mortality or hospitalization for fatal and non-fatal myocardial infarction [MI] or heart failure) (HR, 0.76; 95% CI, 0.58-1.00) and a 42% reduction in hospitalization for MI (HR, 0.58, 95% CI, 0.37-0.92). In patients with heart rate > or =70 b.p.m., there was a 73% reduction in hospitalization for MI (HR, 0.27, 95% CI, 0.11-0.66) and a 59% reduction in coronary revascularization (HR, 0.41, 95% CI, 0.17-0.99). Ivabradine was safe and well tolerated.

Conclusion: Our analyses raises the possibility that ivabradine may be helpful to reduce major cardiovascular events in patients with stable CAD and LVSD who present with limiting angina. However, a large-scale clinical trial is ongoing, which will formally test this hypothesis.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angina Pectoris / drug therapy*
  • Angina Pectoris / mortality
  • Anti-Arrhythmia Agents / therapeutic use*
  • Arrhythmias, Cardiac / drug therapy*
  • Arrhythmias, Cardiac / mortality
  • Benzazepines / therapeutic use*
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / prevention & control*
  • Death, Sudden, Cardiac
  • Double-Blind Method
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Ivabradine
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Ventricular Dysfunction, Left / mortality
  • Ventricular Dysfunction, Left / prevention & control*
  • Young Adult

Substances

  • Anti-Arrhythmia Agents
  • Benzazepines
  • Ivabradine