Rationale and design of a randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction: the morBidity-mortality EvAlUaTion of the I f inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction (BEAUTIFUL) Study

Abstract

Raised resting heart rate (HR) is associated with increased cardiovascular and total mortality. Ivabradine is a new specific HR-reducing agent, which has been shown to have antianginal and anti-ischemic properties in patients with stable angina. Because patients with coronary artery disease and left ventricular dysfunction are at high risk of cardiac events and death, we hypothesized that they could derive particular benefit from a specific HR-lowering agent such as ivabradine. BEAUTIFUL is a multicenter, randomized, international, double-blind placebo-controlled trial to evaluate the superiority of ivabradine over placebo in reducing cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction < or = 39%). The primary end point is the composite of cardiovascular mortality and hospital admission for acute myocardial infarction or new onset or worsening of heart failure. This event-driven study will randomize 9650 patients and continue until 950 primary end points have occurred, providing 90% power to detect a 19% reduction in relative risk. In approximately 660 centers, men and women aged > or = 55 years if nondiabetic and > or = 18 years if diabetic are randomized to placebo or oral ivabradine (5 mg twice daily for 2 weeks then target dose of 7.5 mg twice daily). Follow-up is expected to last between 18 and 36 months. The first patient was randomized in January 2005. BEAUTIFUL will be the first major outcome trial of a specific HR-reducing agent. The study results are expected in 2008.