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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

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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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