Heart rate reduction with ivabradine in heart failure

Abstract Ivabradine inhibits hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, and thereby the ‘funny’ channel If, leading to heart rate reduction, which is dependent on the baseline heart rate. Heart failure treatment should be optimized, in addition to guideline-directed and recommended drugs, to achieve an appropriate heart rate (i.e. 50–60 bpm) with use of ivabradine in patients with a heart rate of >70 bpm in sinus rhythm and with an ejection fraction of ≤35% (SHIFT trial). In this trial, heart rate reduction reduced cardiovascular death and heart failure hospitalization, dependent on the baseline resting heart rate. In particular, in patients with a heart rate of >75 bpm, a reduction in cardiovascular death, all-cause death, heart failure death, heart failure hospitalization, and all-cause hospitalization was observed. The optimal heart rate achieved appears to be between 50 and 60 bpm, if well tolerated, as in these patients, the lowest event rate is observed on treatment. Heart rate reduction is therefore a treatable risk factor in chronic heart failure. Observational studies support the concept that it is a risk indicator in other cardiovascular and non-cardiovascular conditions. Whether heart rate reduction is also modifying the risk in conditions other than chronic heart failure should be explored in prospective clinical trials.