Pure heart rate reduction: further perspectives in heart failure

In patients with symptomatic chronic heart failure, treatment with a beta-blocker has been shown to reduce mortality and sudden cardiac death, and major heart failure guidelines strongly recommend this treatment (Class I level of evidence A). It is believed that at least part of their benefit is related to their effect on heart rate. Many heart failure patients, however, still do not receive a beta-blocker, probably because the side effects of these agents limit their use in some, otherwise eligible, subjects. Furthermore, up-titration of beta-blockers is also suboptimal because of the resultant side effects, such as hypotension and fatigue. Medication that has heart rate-lowering properties similar to those of beta-blockers but without their side effects is, therefore, desirable for patients with heart failure. Ivabradine, a heart rate-lowering agent that acts specifically on the If current of cardiac pacemaker cells in the sinus node without affecting other cardiac ionic currents, offers a new therapeutic possibility in heart failure. Several studies have shown that ivabradine has a unique pharmacodynamic profile, as it results in heart rate reduction without vasodilation or negative inotropic effects, and has been found to have beneficial effects on cardiac remodelling, capillary density, and left ventricular dysfunction. The ongoing SHIFT trial will assess the prognostic value of pure heart rate reduction in heart failure patients.