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

Clinical Research in Cardiology volume 102, pages 11–22 (2013)Cite this article

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.

Conclusion

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.

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Acknowledgments

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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Authors and Affiliations

  1. Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Kirrberger Str. 1, 66424, Homburg/Saar, Germany

    Michael Böhm & Jan-Christian Reil

  2. Division of Cardiovascular Medicine and the Howard Gilman Institute for Heart Valve Disease, State University of New York Downstate Medical Center, Brooklyn, NY, USA

    Jeffrey Borer

  3. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK

    Ian Ford

  4. Cardiology Department, University Hospital, Santiago de Compostela, Spain

    Jose R. Gonzalez-Juanatey

  5. Department of Cardiology, University Pierre et Marie Curie Paris VI, La Pitié-Salpétrière Hospital, Paris, France

    Michel Komajda

  6. Cardiology Department, Hospital Universitario La Paz, IdiPaz, UAM, Madrid, Spain

    Jose Lopez-Sendon

  7. Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden

    Karl Swedberg

  8. Maria Cecilia Hospital, GVM Care and Research, Ettore Sansavini Health Science Foundation, Cotignola, Italy

    Luigi Tavazzi

Authors
  1. Michael Böhm
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  2. Jeffrey Borer
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  3. Ian Ford
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  4. Jose R. Gonzalez-Juanatey
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  5. Michel Komajda
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  6. Jose Lopez-Sendon
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  7. Jan-Christian Reil
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  8. Karl Swedberg
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  9. Luigi Tavazzi
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Corresponding authors

Correspondence to Michael Böhm or Jan-Christian Reil.

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Böhm, M., Borer, J., Ford, I. et al. Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure: analysis from the SHIFT study. Clin Res Cardiol 102, 11–22 (2013). https://doi.org/10.1007/s00392-012-0467-8

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  • DOI: https://doi.org/10.1007/s00392-012-0467-8

Keywords

  • Heart failure
  • Heart rate
  • Cardiovascular outcomes
  • Systolic dysfunction
  • Ivabradine