Ivabradine + Carvedilol Reduces Heart Rate, Ups Exercise Capacity in Patients with CHF

SAN FRANCISCO, CA—The addition of ivabradine resulted in a shorter titration period for carvedilol, a higher final carvedilol dose, a greater reduction in heart rate, and better exercise capacity in patients with chronic heart failure (CHF), according to results of study presented at ACC.13, the American College of Cardiology's 62nd Annual Scientific Session.

The European Society of Cardiology guidelines recommend ivabradine, a specific If current inhibitor, for patients with CHF and an elevated heart rate who are on evidence-based or maximum tolerated doses of beta-blocker and renin-angiotensin-aldosterone system (RAAS) antagonists, stated A. E. Bagriy, MD, of the Donetsk National Medical University of Maxim Gorky, Donetsk, Ukraine, and colleagues.

However, many patients tolerate beta-blockers poorly and few reach target dose,” he added.

The up titration of carvedilol alone (n=21) or with ivabradine (n=21) was compared in 41 patients (27 men), in sinus rhythm who had a previous myocardial infarction, CHF (NYHA Class II-III), and a heart rate ≥70bpm. Participants had not taken a beta-blocker for ≥2 months and were ivabradine-naïve.

Patients were divided into two groups, 21 patients in the carvedilol arm, and 20 patients in the carvedilol + ivabradine arm. Dr. Bagriy initiated carvedilol 3.125mg twice daily in addition to standard therapy, which was doubled every two weeks up to 25mg twice daily or maximum tolerated dose. Ivabradine 5mg twice daily was prescribed 1-2 days after carvedilol was initiated, and titrated to 7.5mg twice daily one month later if the heart rate was ≥70bpm. The final visit occurred at 3 months.

The addition of carvedilol to ivabradine resulted in more than twice the number of patients attaining ≥50% of the carvedilol target dose: 8 patients (38%) in the carvedilol alone arm vs. 16 (80%) in the combination arm (P<0.05). Duration of carvedilol up titration was 2.7 ± 0.7 months vs. 1.9 ± 0.5 months, and the final dose of carvedilol was 29.6 ± 6.2mg/day vs. 37.4 ± 8.4mg/day, respectively (both P<0.05). The reduction in heart rate was 7.2 ± 2.4bpm in the carvedilol alone arm vs. 12.9 ± 3.5bpm in the combination arm (P<0.05) and change in distance in the 6-minute walking test, 32.4 ± 11.7 vs. 68.3±12.7 meters (P<0.05).

“The most common reasons for not reaching beta-blocker target dose were hypotension, dizziness, and worsening CHF,” they concluded.