Occurrence of composite cardiac endpoints with change in resting heart rate among Chinese patients with coronary artery disease: Chinese cohort from the real-world BISO-CAD study

Abstract

Objective: We evaluated change in resting heart rate (RHR) and its impact on prognosis in Chinese coronary artery disease (CAD) patients treated with bisoprolol, and also assessed drug safety and tolerability.

Methods: This phase IV, single arm observational study was a sub-study of the BISO-CAD study conducted across 20 hospitals in China between October 2011 and July 2015 with follow-up at 6, 12 and 18 months after baseline. The primary endpoint was occurrence of composite cardiac events.

Results: A total of 663 CAD patients (baseline RHR 75.47 ± 6.62 bpm) were enrolled in the intent-to-treat (ITT) set, and 513 patients were included in the efficacy analysis (EA) set. In the ITT set, the risk and the number of composite cardiac events in patients with mean RHR 69–74 bpm were significantly higher than in the <65 bpm group (ITT: estimate 1.03 ± 0.47, p = .029). The incidence of the composite cardiac endpoint was not affected by continuous mean RHR (p = .5070). RHR significantly decreased from baseline to 18 months, most obviously in the first 6 months (p < .0001). Ejection fraction and fractional shortening significantly improved in both the ITT and EA sets. An average RHR of 69–74 bpm had a significant effect on admission to hospital for acute coronary syndrome in the ITT (estimate 1.10, HR 3.004, p = .0196) and EA (estimate 1.26, HR 3.526, p = .0132) groups. Seven (1.1%) patients reported drug related adverse events.

Conclusion: Reduction in RHR with bisoprolol lowered the incidence of composite cardiac events along with an acceptable safety and tolerability profile.

Keywords:

• Resting heart rate
• coronary heart disease
• bisoprolol
• Chinese cohort
• composite cardiac endpoint

Note

Transparency

Declaration of funding

The study was funded by Merck Serono Co. Ltd, an affiliate of Merck KGaA, Darmstadt, Germany.

Author contributions: All the authors planned the analysis and contributed to the interpretation of the data, revisions, and gave input at all stages of the analysis. All the authors have approved the final version of the manuscript.

Declaration of financial/other relationships

H.X. has disclosed that she was employed by Merck Serono China R&D, Beijing, China during the study period. T.M. has disclosed that he was employed by Merck Serono Co. Ltd China, an affiliate of Merck KGaA Darmstadt, Germany. Y.C., X.Y., S.H., G.F., X.C., Y.Ya., S.L., X.Z., Z.L., M.Y., X.G., D.X., F.C., H.L., J.L., Q.Z., N.W., Y.Yu., W.L. and T.Y. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The authors acknowledge Dr. Dhanya Mukundan and Karan Sharma (Indegene, Bangalore, India) for providing medical writing support and technical assistance in the development of this manuscript, as funded by Merck Serono Co. Ltd, China, an affiliate of Merck KGaA, Darmstadt, Germany.

Notes

1 Concor is a registered trade name of Merck Serono Co. Ltd.