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Heart rate reduction in coronary artery disease and heart failure

Key Points

  • The role of heart rate in coronary artery disease and heart failure has been explored using ivabradine, a drug that selectively targets heart rate

  • Increased heart rate can provoke myocardial ischaemia

  • Heart rate reduction can reduce the symptoms of angina

  • Increased heart rate is a risk marker in patients with coronary artery disease, but heart rate reduction does not improve prognosis in this clinical setting

  • In the setting of heart failure, elevated heart rate is a modifiable risk factor — reducing heart rate improves prognosis in these patients

  • Excessive bradycardia can cause dispersion of atrial fibrillation

Abstract

Elevated heart rate is known to induce myocardial ischaemia in patients with coronary artery disease (CAD), and heart rate reduction is a recognized strategy to prevent ischaemic episodes. In addition, clinical evidence shows that slowing the heart rate reduces the symptoms of angina by improving microcirculation and coronary flow. Elevated heart rate is an established risk factor for cardiovascular events in patients with CAD and in those with chronic heart failure (HF). Accordingly, reducing heart rate improves prognosis in patients with HF, as demonstrated in SHIFT. By contrast, data from SIGNIFY indicate that heart rate is not a modifiable risk factor in patients with CAD who do not also have HF. Heart rate is also an important determinant of cardiac arrhythmias; low heart rate can be associated with atrial fibrillation, and high heart rate after exercise can be associated with sudden cardiac death. In this Review, we critically assess these clinical findings, and propose hypotheses for the variable effect of heart rate reduction in cardiovascular disease.

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Figure 1: Beneficial effects of heart rate reduction in angina.
Figure 2: Beneficial effects of heart rate reduction in heart failure.
Figure 3: Molecular explanation for the effects of ivabradine independent of heart rate reduction.
Figure 4: Effects of heart rate increase in various cardiovascular disease states.

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Acknowledgements

This work was supported by a grant from Fondazione Anna Maria Sechi per il Cuore (FASC), Italy. FASC had no role in the decision to publish or the preparation of the manuscript.

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Both authors contributed equally to researching data, discussion of content, writing the article, and reviewing and editing the manuscript before submission.

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Correspondence to Roberto Ferrari.

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R.F. declares having received honoraria from Servier for steering committee membership, consulting, and speaking, and support for travel to study meetings from Servier. In addition, he received personal fees from Amgen, Boehringer Ingelheim, Irbtech, Merck Serono, and Novartis. K.F. declares having received fees, honoraria, and research grants from Servier.

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Ferrari, R., Fox, K. Heart rate reduction in coronary artery disease and heart failure. Nat Rev Cardiol 13, 493–501 (2016). https://doi.org/10.1038/nrcardio.2016.84

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