title: Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure: analysis from the SHIFT study.
abstract: BACKGROUND
  We analysed the effect of ivabradine on outcomes in heart failure (HF) patients on recommended background therapies with heart rates ≥75 bpm and <75 bpm in the SHIFT trial. A cut-off value of ≥75 bpm was chosen by the EMEA for approval for the use of ivabradine in chronic heart failure.
  
  
  METHODS
  The SHIFT population was divided by baseline heart rate ≥75 or <75 bpm. The effect of ivabradine was analysed for primary composite endpoint (cardiovascular death or HF hospitalization) and other endpoints.
  
  
  RESULTS
  In the ≥75 bpm group, ivabradine reduced primary endpoint (HR 0.76, 95 % CI 0.68-0.85, P < 0.0001), all-cause mortality (HR 0.83, 95 % CI, 0.72-0.96, P = 0.0109), cardiovascular mortality (HR 0.83, 95 % CI, (0.71-0.97, P = 0.0166), HF death (HR 0.61, 95 % CI, 0.46-0.81, P < 0.0006), and HF hospitalization (HR 0.70, 95 % CI, 0.61-0.80, P < 0.0001). Risk reduction depended on heart rate after 28 days, with the best protection for heart rates <60 bpm or reductions >10 bpm. None of the endpoints was significantly reduced in the <75 bpm group, though there were trends for risk reductions in HF death and hospitalization for heart rate <60 bpm and reductions >10 bpm. Ivabradine was tolerated similarly in both groups.
  
  
  CONCLUSIONS
  The effect of ivabradine on outcomes is greater in patients with heart rate ≥75 bpm with heart rates achieved <60 bpm or heart rate reductions >10 bpm predicting best risk reduction. Our findings emphasize the importance of identification of high-risk HF patients by high heart rates and their treatment with heart rate-lowering drugs such as ivabradine.
authors.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Kirrberger Str. 1, 66424, Homburg/Saar, Germany. michael.boehm@uks.eu
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Borer
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.forename: Jose R
authors.initials: JR
authors.lastname: Gonzalez-Juanatey
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Sendon
authors.forename: Jan-Christian
authors.initials: JC
authors.lastname: Reil
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006339:Heart Rate; D006760:Hospitalization; D006801:Humans; D000077550:Ivabradine; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D000077550:Ivabradine