Heart rate control is associated with reduced cardiovascular events in Asian patients with coronary artery disease treated with bisoprolol (BISO-CAD): results from a multi-national, real-world experience

Abstract

Objective: To evaluate the association between decrease in resting heart rate (RHR) and occurrence of composite cardiac clinical outcomes in coronary artery disease (CAD) patients after bisoprolol treatment.

Methods: This phase IV, multi-national, single-arm, open-label, non-randomized, observational trial was conducted between October 2011 and July 2015 across 42 hospitals from China, South Korea and Vietnam.

Results: Analysis of 866 patients (mean age 63.85 ± 10.35; mean RHR at baseline 75.71 ± 6.87 bpm in intent-to-treat [ITT]; 75.56 ± 6.73 in efficacy analysis [EA] sets) was performed. Patients with lower mean RHR had fewer composite cardiac events and patients with RHR of 69–74 bpm reported significantly higher outcomes than patients with RHR <65 bpm (p = .0449). A significant association with occurrence of the composite cardiac outcome and hospital admission for unstable angina or revascularization was reported in the EA set (regression estimate: 0.03, 95% CI 0.00–0.07, p = .0412) and not in the ITT set for bisoprolol treated CAD patients. Composite cardiac outcomes significantly increased in patients with mean RHR ≥70 bpm compared to patients with mean RHR <70 bpm (p = .0328). Adverse events (AEs) were reported in 206 (23.8%) patients, of whom 102 (11.8%) patients had serious adverse event (SAEs). Among the patients with SAEs, 11 (1.3%) patients died. Treatment related adverse events were only 12 (1.4%). No treatment related SAE happened.

Conclusion: The findings showed bisoprolol to be efficacious, in terms of lowering RHR and causing a significant decrease in the occurrence of the composite cardiac outcome, as well as safe in Asian patients with CAD.

Keywords:

• Bisoprolol
• coronary artery disease
• phase IV

Note

Transparency

Declaration of funding

The study was funded by Merck Sereno 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.

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

Declaration of financial/other relationships

Y.C., X.Y., V.N.P., S.H., G.F., X.C., B.Q.T, Y.Y., S.L., X.C., T.M., D.-S.K. and T.K. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

Acknowledgements

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

Notice of correction

Please note that Figure 1 has been edited since the paper was first published (1 September 2017).

Notes

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