Role of Ivabradine in the Treatment of Patients With Cardiovascular Disease

OBJECTIVE: To review the role of heart rate in myocardial ischemia and heart failure with reduced ejection fraction (HFrEF) as well as ivabradine's pharmacology and pharmacokinetics, clinical trials, and place in therapy. DATA SOURCES: We conducted MEDLINE searches from 1980 to October 2015 using the terms heart failure, HFrEF, angina, f-channel inhibitor, and ivabradine, with forward and backward citation tracking. STUDY SELECTION AND DATA EXTRACTION: English-language trials assessing ivabradine were obtained. Studies and narrative reviews of the topic areas were incorporated if they provided relevant data to inform the practicing clinician. DATA SYNTHESIS: In the SIGNIFY (Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients with Coronary Artery Disease) trial, there was no difference in the primary composite end point of cardiovascular (CV) mortality or nonfatal myocardial infarction with ivabradine use in patients with stable coronary artery disease (CAD) versus placebo (P = 0.20). In the subgroup with Canadian Cardiovascular Society angina class ≥II, there was an 18% increase in the primary end point with ivabradine versus placebo (P = 0.02). In HFrEF patients, ivabradine reduced CV mortality or heart failure hospitalizations versus placebo, as seen in the SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial; P < 0.05). CONCLUSIONS: The SIGNIFY trial negated much of the enthusiasm for using ivabradine in CAD. Ivabradine is a promising therapy in HFrEF based on the results of the SHIFT, but it is an adjunctive therapy, not a substitute for drugs with proven mortality benefits.