Author + information
- Chen Yundai1,
- Vinh Nguyen Pham2,
- Shian Huang3,
- Dongsoo Kim4,
- Tianrong Ma5,
- Xinchun Yang6 and
- Yundai Chen1
This study was to evaluate the association between mean resting heart rate (RHR) and prognosis of coronary artery disease (CAD) in Asian patients treated with bisoprolol.
Between October 2011 and April 2014, this observational, phase 4 study enrolled 889 patients with CAD from 40 hospitals in China, South Korea and Vietnam. The primary endpoint was occurrence of composite cardiovascular (CV) events (CV death, non-fatal acute myocardial infarction and hospitalisation for unstable angina or revascularisation) during 18-month bisoprolol treatment. Exploratory analyses of the primary endpoint compared the occurrence of composite CV events in different RHR groups (<70 vs. ≥70 bpm), and evaluated the association between the change in RHR (high-low, i.e. from ≥70 to <70bpm; and high-high, i.e. from ≥70 to ≥70bpm) and CV events. Relationship between HR and CV events was analysed using Poisson regression. Secondary endpoints were changes in RHR, heart function, intima media thickness (IMT), mortality; hospitalisation due to acute coronary syndrome (ACS) and coronary revascularisation and occurrence of cerebral events. Relationship between HR and secondary endpoints was analysed with a mixed model repeated measures or cox proportional hazard model.
Intent-to-treat (ITT) set included 866 patients with CAD (mean age: 63.85±10.35 years, mean BMI 25.45±3.19 kg/m2) and per protocol (PP) set included 688 patients. Totally 178 patients were excluded from PP set due to violation of eligibility criteria (3) and early termination but without CV events (175). Mean dose of bisoprolol was 3.63±1.90 mg for a mean duration of 522.8±133.6 days. In all, 45% and 38.7% of patients were treated with doses of 2.5 and 5 mg, respectively. In PP set, lower mean RHR was significantly associated with less occurrence of composite CV events (estimate: 0.03 [95%CI: 0.00-0.07], p=0.0412). ITT set did not report any significant association between RHR and CV events (estimate: 0.02 [95%CI: 0.02-0.05], p=0.3114). Exploratory analyses showed significantly low occurrence of CV events in subjects with a mean HR <70 bpm than those with a mean HR ≥70 bpm (p=0.0328) in PP set. Patients with a change of RHR categorised in high-low group had less occurrence of composite CV events than those categorised in high-high group (p<0.0001) in PP set. For secondary endpoints, higher level of RHR was significantly associated with all-cause mortality in ITT (HR: 1.077, p=0.0024) and PP (HR: 1.077, p=0.013). Subgroup analyses showed lower RHR was significantly associated with less CV events in patients aged ≥70 years in both ITT (estimate: 0.07 [95%CI: 0.01-0.13], p=0.0195) and PP (estimate: 0.11 [95%CI: 0.04-0.17], p=0.0008).
Reduction in RHR after bisoprolol treatment lowered the incidence of composite CV events in Asian patients with CAD, which was of significance for patients aged ≥70 years. Controlling RHR <70 bpm helped improve prognosis in patients with CAD and dose of bisoprolol needed to be further optimised.