Clinical Research in Cardiology

, Volume 102, Issue 1, pp 11–22 | Cite as

Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure: analysis from the SHIFT study

  • Michael BöhmEmail author
  • Jeffrey Borer
  • Ian Ford
  • Jose R. Gonzalez-Juanatey
  • Michel Komajda
  • Jose Lopez-Sendon
  • Jan-Christian ReilEmail author
  • Karl Swedberg
  • Luigi Tavazzi
Original Paper



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.


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.


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.


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.


Heart failure Heart rate Cardiovascular outcomes Systolic dysfunction Ivabradine 



MB and JCR were supported by the Ministry of Science of the federal state of the Saarland, Germany, and the Deutsche Forschungsgemeinschaft (KFO 196).


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Michael Böhm
    • 1
    Email author
  • Jeffrey Borer
    • 2
  • Ian Ford
    • 3
  • Jose R. Gonzalez-Juanatey
    • 4
  • Michel Komajda
    • 5
  • Jose Lopez-Sendon
    • 6
  • Jan-Christian Reil
    • 1
    Email author
  • Karl Swedberg
    • 7
  • Luigi Tavazzi
    • 8
  1. 1.Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische IntensivmedizinUniversitätsklinikum des SaarlandesHomburg/SaarGermany
  2. 2.Division of Cardiovascular Medicine and the Howard Gilman Institute for Heart Valve DiseaseState University of New York Downstate Medical CenterBrooklynUSA
  3. 3.Robertson Centre for BiostatisticsUniversity of GlasgowGlasgowUK
  4. 4.Cardiology DepartmentUniversity HospitalSantiago de CompostelaSpain
  5. 5.Department of CardiologyUniversity Pierre et Marie Curie Paris VI, La Pitié-Salpétrière HospitalParisFrance
  6. 6.Cardiology DepartmentHospital Universitario La Paz, IdiPaz, UAMMadridSpain
  7. 7.Department of Molecular and Clinical Medicine, Sahlgrenska AcademyUniversity of GothenburgGöteborgSweden
  8. 8.Maria Cecilia Hospital, GVM Care and Research, Ettore Sansavini Health Science FoundationCotignolaItaly

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