Tolerability of nebivolol in head-to head clinical trials vs. other cardioselective beta-blockers in the treatment of hypertension. A meta-analysis.

Objective: To assess the comparative tolerability of nebivolol and other cardioselective -blockers (CSBs) in the treatment of mild-to-moderate hypertension.Data source: Database searches of MEDLINE, EMBASE, and the Cochrane Controlled Trials Register up to August 2004 identified randomised clinical trials comparing nebivolol and other CSBs in patients with mild-to-moderate hypertension, with a treatment duration of at least 4 weeks and reporting any tolerability data.Design and methods: Baseline and post-intervention data on tolerability and efficacy were extracted from the studies. Tolerability was assessed by the rate of patients with adverse events (AEs), the total number of AEs and the number of drug-related AEs. Efficacy endpoints were the changes from baseline in diastolic and systolic blood pressure and the rate of treatment responders. For meta-analysis of data presenting relative frequency or means and standard deviations, the random effects model for proportions and means was applied. Absolute frequency data were normalised to the expected frequencies in 1000 patients and analysed by methods for comparison of Poisson distributed data. The quality of each trial was evaluated using a pre-defined checklist reflecting the basic potency of a selected study to detect the relative tolerability of the drugs investigated. The final analysis was performed in the high-quality studies; the low-quality studies were included, where appropriate, in robustness analysis.Results: Ten trials comparing nebivolol with the CSBs atenolol, metoprolol or bisoprolol were selected. According to the pre-defined criteria, three studies were assessed as high-quality studies and seven as low-quality studies. The ratio of the rates of patients with AEs treated with nebivolol compared with those treated with the CSBs was 0.63 (95% CI 0.44, 0.91). The difference of the rates of patients with AEs reached -12.8% (95% CI -23.3%, -2.3%). The ratio of normalised total AEs was 0.71 (95% CI 0.62, 0.82), and the ratio of normalised drug-related AEs was 0.38 (95% CI 0.29, 0.50). In the expected frequencies of AEs in 1000 patients, the differences in number of normalised total AEs and drug-related AEs with nebivolol compared with the other CSBs were -147 (95% CI -205, -89) and -126 (95% CI -159, -93), respectively. In the efficacy meta-analysis, nebivolol was at least as effective as the other CSBs.Conclusions: This meta-analysis revealed that the tolerability of nebivolol is superior to that of atenolol, metoprolol and bisoprolol, and confirmed that nebivolol is at least as effective as these CSBs in the treatment of mild-to-moderate hypertension. The treatment of mild-to-moderate essential hypertension with antihypertensive drugs that have a relatively favourable tolerability profile, such as nebivolol, may be a way to improve persistence with antihypertensive treatment and overcome the consequences of poor compliance.