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.