Bisoprolol Initiation in Heart Failure Patients by Primary Care Physicians Effective – A Prospective Study
Bisoprolol Initiation in Heart Failure Patients by Primary Care Physicians Effective – A Prospective Study
Introduction
Beta-blockers have demonstrated NYHA functional class reduction in patients with heart failure with reduced ejection fraction (HFrEF). In addition, they have also shown demonstrated mortality reduction in HFrEF. Therefore, they are recognized as class I drugs in the management of HFrEF. However, primary care physicians (PCPs) do not prescribe beta-blockers in all HFrEF patients. Moreover, even when beta-blockers are prescribed in patients with HFrEF, the dosages used by the PCPs are often lower than the target dose demonstrated in the clinical trials.
Because the clinical trials of beta-blockers were conducted in teaching institutions and not in the primary care, studies demonstrating beta-blocker initiation in HFrEF patients by the PCPs have been recommended. Such studies may potentially improve the adoption and utilization of beta-blockers by the PCPs in patients with HFrEF, and thus improve their cardiovascular outcomes.
Aims
In this prospective study, Schuchert et al.1 aimed to investigate the efficacy and safety of bisoprolol initiated by the PCPs for the treatment of HFrEF in the outpatient setting. Specifically, the authors aimed to investigate the effects of bisoprolol on the NYHA functional class, heart rate, and blood pressure. Additionally, they aimed to assess the safety in terms of the frequency of adverse events.
Methods
In this prospective study from Germany, adults aged 18-80 years with HFrEF with at least 6 weeks duration receiving basic therapy with renin angiotensin system inhibitors (RASIs) and diuretics were included between September 1999 and May 2000. In contrast, patients with acute or decompensated cardiac failure, unstable cardiovascular conditions, and recent cardiovascular events were excluded. Patients with systolic blood pressure < 100 mmHg, bradycardia below 60 beats per min, or AV-block II or III or sick sinus syndrome were also excluded. Patients with significant renal impairment, poorly controlled diabetes mellitus, known contra-indications for beta-blockers or bisoprolol, pregnancy or lactation were also excluded. The study duration was 24 weeks including a 11-week titration phase followed by a maintenance phase. The titration schedule was as follows: Initiation with 1.25 mg per day, 2.5 mg after week 1, 3.75 after week 2, 5 mg after week 3, 7.5 mg after week 7, and 10 mg after week 11. Likewise, any adverse-event related dose reduction was also in a stepwise manner by halving the dose. Change in NYHA functional class was the primary study endpoint. Patients were evaluated for NYHA functional class, heart failure symptoms, heart rate, and blood pressure at 7, 19, and 24 weeks. This study was conducted in accordance with the Declaration of Helsinki. This study was approved by an independent ethics committee and by local ethics committees.
Summary of Key Results
A total of 328 HFrEF patients were included in this study who were initiated with bisoprolol by 184 PCPs. The mean age of the included patients was 63 years and 68% of them were males. A total of 48% patients had hypertension and 37% had coronary artery disease. Hyperlipidemia (25%) and diabetes (21%) were the commonest non-cardiac comorbidities. All patients received diuretics and RASIs. On baseline ECG, 80% had normal rhythm, 15% had atrial fibrillation, and 5% had pacemaker rhythm. The baseline NYHA functional class distribution was as follows: 174 in NYHA class II, 145 in Class III, and 1 in class IV.
Patients received bisoprolol for a mean of 189 days in this study. A mean maximal dose of 7.2 mg per day was reached within a mean of 65 days. The distribution of maximal tolerated dose in this study is shown in Figure 1. As can be noted from Figure 1, the majority of patients (61%) received the 10-mg- or 7.5mg-daily dose of bisoprolol.
Figure 1. Maximal Dose Distribution in the Study.1
Over the study period, 74% patients reported an improvement in the NYHA class. Moreover, the NYHA functional class of the patients consistently improved at each visit from a mean of 2.4 at the beginning of the study to 1.8 at 19 weeks, which then stabilized until 24 weeks (p<0.001) (Figure 2). In addition, the improvement in the NYHA class was significantly higher in the patients with the baseline NYHA class of 3 than in patients with baseline NYHA class 2.
Figure 2. NYHA Class of Patients over the Study.1
Regarding the changes in heart rate and blood pressure, significant reductions were noted from the first week itself (heart rate had a reduction by a mean of 7.7, while systolic and diastolic blood pressures reduced by a mean of 5.8 and 3.3 mmHg, respectively; p<0.0001 for both heart rate and blood pressure reductions). The respective mean reductions in the heart rate and systolic and diastolic blood pressure at study completion were 14.5, 9.1, and 4.5 (p<0.0001 for both heart rate and blood pressure reductions).
Regarding safety outcomes, 83% patients continued with the bisoprolol treatment while 57 (17%) had a permanent withdrawal of bisoprolol, of which 40 (12%) discontinued it due to adverse events. Six serious adverse events were reported. At least one hospitalization was reported in 38 patients.
Discussion and Conclusion
The authors highlighted that they were able to demonstrate the effectiveness of bisoprolol in HFrEF in terms of improvement of NYHA class, blood pressure and heart rate reductions, reaching maximal doses, and the low incidence of adverse events. Moreover, their results for efficacy and safety of bisoprolol were more or less similar to that of CIBIS II trial despite their study was conducted in the outpatient setting, and bisoprolol was initiated and followed-up by the PCPs in this study unlike the hospital-based clinical trial setting.
The authors concluded that they were able to successfully demonstrate the feasibility of the initiation of bisoprolol in HFrEF patients in the outpatient setting and that their approach was safe and effective. They recommended a wider adoption of their approach in practice to improve cardiovascular outcomes and reduce healthcare costs.
References
1. Schuchert A; BISEX Investigators. Effects of bisoprolol treatment for chronic heart failure initiated and followed up by primary care physicians. Eur J Heart Fail. 2005;7(4):604-611.