If Inhibitor

The ‘funny’ current (If) was first described in sinoatrial node myocytes in 1979. This current is a mixed sodium/potassium inward current, which is activated on hyperpolarisation at voltages in the diastolic range.Increased resting heart rate (HR) is a risk factor for the development of cardiovascular events in patients with known cardiovascular disease. HR reduction by β blockers is a beneficial treatment for improving the prognosis in patients with myocardial infarction and heart failure. Therefore, HR reduction by inhibition of the If current may be a suitable therapeutic option in patients with heart failure. A novel selective If inhibitor, ivabradine, is a pure HR-lowering agent. The BEAUTIFUL trial conducted in 10,917 patients with coronary artery disease and a left ventricular ejection fraction (LVEF)<40% showed no difference between the ivabradine and placebo groups in the rate of the composite endpoint of cardiovascular death, hospitalization for acute myocardial infarction, or for new-onset or worsening heart failure. In a subgroup of patients with HR≥70 bpm, however, ivabradine reduced hospitalization for myocardial infarction and for coronary revascularization. The SHIFT trial conducted in 6,505 stable heart failure patients with a LVEF≤35% and a HR≥70 bpm demonstrated that the rate of the composite endpoint of cardiovascular mortality and hospitalization for worsening heart failure was significantly lower in the ivabradine group than in the placebo group. This study showed the importance of HR reduction with ivabradine for improving clinical outcomes in heart failure. (Jpn J Clin Pharmacol Ther 2012; 43(5): 331-338)