title: Twenty-four-hour heart rate lowering with ivabradine in chronic heart failure: insights from the SHIFT Holter substudy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany.
authors: Michael
authors: M
authors: Böhm
authors: Jeffrey S
authors: JS
authors: Borer
authors: John
authors: J
authors: Camm
authors: Ian
authors: I
authors: Ford
authors: Suzanne M
authors: SM
authors: Lloyd
authors: Michel
authors: M
authors: Komajda
authors: Luigi
authors: L
authors: Tavazzi
authors: Mario
authors: M
authors: Talajic
authors: Mitja
authors: M
authors: Lainscak
authors: Jan-Christian
authors: JC
authors: Reil
authors: Christian
authors: C
authors: Ukena
authors: Karl
authors: K
authors: Swedberg
mesh_terms: D000368:Aged; D001552:Benzazepines / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D015716:Electrocardiography, Ambulatory / Q000379:methods*; D005260:Female; D054143:Heart Failure, Systolic / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D001552:Benzazepines; D002317:Cardiovascular Agents; D000077550:Ivabradine
keywords: 24-h heart rate; Heart failure; Heart rate; Ivabradine; Left ventricular dysfunction; Night-time heart rate