Role of Heart Rate in Cardiovascular Diseases

Abstract

The BEAUTIFUL (morBidity-mortality EvAlUaTion of the If inhibitor ivabradine in patients with coronary artery disease and left ventricULar systolic dysfunction) study assessed the morbidity and mortality benefits of the HR-lowering agent ivabradine. The placebo arm of the BEAUTIFUL trial was a large cohort of patients with stable coronary artery disease (CAD) and left ventricular systolic dysfunction. A subanalysis in the placebo group tested the hypothesis that elevated resting HR at baseline was a marker for subsequent cardiovascular death and morbidity. The primary aim of the study was to test whether lowering the HR with ivabradine reduced cardiovascular death and morbidity in patients with CAD and left ventricular systolic dysfunction. In the overall analysis, reduction in HR with ivabradine did not improve cardiac outcomes compared with placebo. The most important finding of the study was that patients with high baseline HR had an increase in serious cardiovascular events including death (34%), hospital admission secondary to congestive heart failure (53%), acute myocardial infarction (46%), or revascularization procedure (38%). In addition, in the subset analysis focusing on patients with baseline HR ≥70bpm and left ventricular ejection fraction <40% the agent resulted in a 36% decrease in hospital admissions secondary to fatal and nonfatal myocardial infarction and a 30% decrease in coronary revascularization. The first practical implication from the study includes that baseline HR should be recorded in addition to other risk factors such as BP and lipid profile, in the follow-up of patients with CAD. Attempts should be made to achieve HR <70 bpm by cardiac rehabilitation and routine use of appropriately dosed β-blockers. Despite the neutral results obtained in the BEAUTIFUL study, ivabradine could be administered to the subgroup of patients in whom HR <70 bpm is not achieved despite proper dosing of β-blockers and in those in whom β-blockers are contraindicated. Furthermore, in clinical practice, ivabradine may be helpful for patients with stable CAD who have a high HR while receiving β-blockers. Future studies are needed to confirm the hypothesis that single reduction of HR can improve cardiovascular prognosis.