Impact of ‘‘Off-Label’’ Use of Ivabradine on Exercise Capacity, Gas Exchange, Functional Class, Quality of Life, and Neurohormonal Modulation in Patients With Ischemic Chronic Heart Failure

Abstract

Background: Epidemiologic studies indicate that elevated heart rate (HR) is an independent risk factor for mortality and morbidity in patients (pts) with chronic heart failure (CHF). Clinical trials with β-blockers suggest that HR reduction is an important mechanism of their benefit in pts with stable CHF. Pharmacologic inhibition of the If current now provides the opportunity of pure HR reduction. The purpose of this study was to evaluate the impact of ‘‘Off-Label’’ use of ivabradine on exercise capacity, gas exchange, functional class, quality of life, and neurohormonal modulation in pts with ischemic CHF. Methods: Between January 2008 and June 2008, a graded maximal exercise test with respiratory gas analysis and an endurance test with constant workload corresponding to 85% of the peak VO2 at the baseline and after 3 months were performed, and at the same times, N-terminal probrain natriuretic peptide (NT-proBNP) levels were also measured, in 60 pts (45 M, 15 F, mean age 52.7 ± 5.3 years), with stable ischemic CHF, New York Heart Association (NYHA) functional classes II (n = 35)—III (n = 25), with left ventricular ejection fraction (LVEF) ≤ 40%, randomized to a ‘‘off-label’’ ivabradine use (n = 30) and a control group (n = 30). Results: The exercise capacity increased from 14.8 ± 2.5 to 28.2 ± 3.5 min (P < .0001) and the peak oxygen consumption tended to improve from 13.5 ± 1.3 to 17.9 ± 2.4 mL/kg per minute (P < .0001) in ivabradine group. Oxygen consumption at the anaerobic threshold (AT) increased from 11.9 ± 1.4 to 15.3 ± 1.4 mL/kg per minute (P < .0001). NTproBNP levels decreased from 2356 ± 2113 pg/mL to 1434 ± 1273 pg/mL (P = .045). No significant differences were found in control group at 3 months. The positive ivabradine effects were also associated with an improvement in the NYHA functional class and quality of life. Conclusion: The ‘‘Off-Label’’ use of ivabradine significantly improves the exercise capacity, gas exchange, functional heart failure class, quality of life, and neurohormonal modulation in pts with ischemic CHF.