Twenty-four-hour heart rate lowering with ivabradine in chronic heart failure: insights from the SHIFT Holter substudy.

Abstract

AIMS:

Analysis of 24-h Holter recordings was a pre-specified substudy of SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial) for exploring the heart rhythm safety of ivabradine and to determine effects of ivabradine on 24-h, daytime, and night-time heart rate (HR) compared with resting office HR.

METHODS AND RESULTS:

The 24-h Holter monitoring was performed at baseline and 8 months after randomization to ivabradine (n = 298) or matching placebo (n = 304) titrated maximally to 7.5 mg b.i.d. in patients with baseline HR ≥70 b.p.m. Patients received guideline-based optimized heart failure therapy including ACE inhibitors and/or ARBs in 93% and beta-blockers at maximally tolerated doses in 93%. After 8 months, HR over 24 h decreased by 9.5 ± 10.0 b.p.m. with ivabradine, from 75.4 ± 10.3 b.p.m. (P < 0.0001), and by 1.2 ± 8.9 b.p.m. with placebo, from 74.8 ± 9.7 b.p.m. (P < 0.0001 for difference vs. ivabradine). HR reduction with ivabradine was similar in resting office and in 24-h, awake, and asleep recordings, with beneficial effects on HR variability and no meaningful increases in supraventricular or ventricular arrhythmias. At 8 months, 21.3% on ivabradine vs. 8.5% on placebo had ≥1 episode of HR <40 b.p.m. (P < 0.0001). No episode of HR <30 b.p.m. was recorded; 3 (1.2%) patients had RR intervals >2.5 s on ivabradine vs. 4 (1.6%) patients on placebo. No RR intervals >3 s were identified in patients taking ivabradine.

CONCLUSION:

Ivabradine safely and significantly lowers HR and improves HR variability in patients with systolic heart failure, without inducing significant bradycardia, ventricular arrhythmias, or supraventricular arrhythmias.

• Authors: Michael Böhm, Jeffrey S Borer, John Camm, Ian Ford, Suzanne M Lloyd, Michel Komajda, Luigi Tavazzi, Mario Talajic, Mitja Lainscak, Jan-Christian Reil, Christian Ukena, Karl Swedberg
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 17 Issue 5 Pg. 518-26 (May 2015) ISSN: 1879-0844 [Electronic] England
• PMID: 25801408 (Publication Type: Journal Article)
• Copyright: © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Chemical References

• Benzazepines
• Cardiovascular Agents
• Ivabradine

Topics

• Aged
• Benzazepines (therapeutic use)
• Cardiovascular Agents (therapeutic use)
• Electrocardiography, Ambulatory (methods)
• Female
• Heart Failure, Systolic (drug therapy)
• Heart Rate (drug effects)
• Humans
• Ivabradine
• Male
• Middle Aged
• Prospective Studies