Overview of large morbidity/mortality trials with ivabradine: Focus on the BEAUTIfUL study

Abstract

Heart failure and left ventricular dysfunction complicating coronary artery disease (CAD) are associated with a poor prognosis. Beta-blockers have been shown to be beneficial for survival in these conditions, a benefit that is mediated, in part, through slowing of the heart rate. In addition, since heart rate is one of the major determinants of myocardial oxygen consumption, its lowering is associated with relief of ischaemia and anginal symptoms, and indeed, slowing the heart rate with beta-blockers is associated with effective relief of ischaemia. Therefore, in left ventricular dysfunction complicating CAD, there is potentially a major role for slowing the heart rate. Although effective, beta-blockers may not always achieve optimal heart rate lowering or may not be well tolerated. Ivabradine, a selective heart rate-lowering agent, is being tested compared with placebo, in addition to standard therapy (including beta-blockers, if tolerated) in the large morbidity/mortality BEAUTI fUL trial. This study was established to test the superiority of ivabradine compared with placebo as an adjunct to conventional therapy in the reduction of a composite endpoint of cardiovascular mortality, acute myocardial infarction (requiring hospital admission), and new or worsening heart failure (requiring hospital admission) in patients with stable CAD, in sinus rhythm, and with left ventricular dysfunction. Approximately 11 000 patients with evidence of CAD, a sinus rhythm of ≥60 bpm, and an ejection fraction of 39% or less were enrolled. In a randomized, double-blind fashion, patients are receiving ivabradine 5 mg twice daily titrated to 7.5 mg twice daily after 2 weeks, or matching placebo, in order to target a heart rate of <60 bpm. Holter electrocardiography, echocardiography, and NT-proBNP substudies are also planned.The BEAUTIfUL trial will be an important step in determining the clinical importance of heart rate on the outcome of patients with CAD and left ventricular dysfunction. © The European Society of Cardiology 2007. All rights reserved.