Rate control with ivabradine

Abstract

The importance of heart rate in human health and disease has been well known to clinicians for quite some time. Recent epidemiologic studies have further strengthened this concept. Modulation of heart rate by pharmacologic as well as non-pharmacologic means has affected cardiovascular mortality and morbidity in various trials and observational studies. Conventional rate-control agents, such as β-adrenoceptor antagonists (β-blockers), calcium channel blockers, and digoxin, have contributed greatly to the management of various diseases where heart-rate reduction is required; however, these agents have effects beyond rate control that may be unacceptable. Ivabradine has recently been recognized as a pure heart-rate-reducing agent and is being extensively studied. It is the latest addition to the class of drugs used to control angina. It is indicated in cases of β-blocker intolerance or when β-blockers fail to achieve a heart rate of <60 beats/min. The pure heart-rate-reducing effect of ivabradine has also been reported in smaller studies and anecdotal case reports. The theoretical possibilities of the utility of ivabradine are many and have opened up a whole new field of research for the future. The BEAUTIFUL trial enrolled approximately 10 000 patients with coronary artery disease (CAD) and left ventricular dysfunction, with the aim of assessing the effect of ivabradine versus atenolol on various cardiovascular outcomes. Although ivabradine failed to achieve favorable results for primary endpoints, it appeared effective in achieving a favorable secondary endpoint in a subgroup of patients who had a heart rate of >70 beats/min. Other large trials are also underway to assess the effects of ivabradine on heart failure, acute coronary syndromes, CAD, and other cardiovascular disorders. In this review, we discuss the pharmacologic basis of the action of ivabradine and its role in angina control, as well as in other conditions being actively studied or in which a role for ivabradine has been hypothesized.