Comparative efficacy and safety of nebivolol in hypertension: a systematic review and network meta-analysis

Background Nebivolol functions as a third-generation, highly selective beta1-adrenoceptor antagonist distinguished by its nitric oxide-inducing vasodilatory capabilities. Purpose The current network meta-analysis (NMA) was designed to appraise the clinical effectiveness and safety profile of nebivolol in contrast to placebo and alternative blood pressure-lowering therapies. Methods A comprehensive literature review was executed across primary databases, including Cochrane CENTRAL, Embase, and PubMed, up to June 2025. The analysis incorporated both randomised and non-randomised controlled trials that evaluated nebivolol against placebo, alternate beta-blockers, or other primary antihypertensive drugs. Following rigorous data extraction and bias risk evaluations, a frequentist NMA was performed via R software. The present findings highlight the comparative outcomes of nebivolol against placebo and other beta-blockers, expressing results as mean differences. Results The systematic review and subsequent NMA comprised 108 individual studies. Administration of 5 mg nebivolol yielded substantial reductions in systolic blood pressure (SBP) of −9.95 mmHg (95% confidence interval [CI]: −15.88 to −4.02) and diastolic blood pressure (DBP) of −5.29 mmHg (95% CI: −7.33 to −3.26) relative to placebo. Subgroup assessments of individuals under 50 years of age showed sustained benefits, with SBP decreasing by −8.50 mmHg (95% CI: −16.99 to −0.01) and DBP by −7.06 mmHg (95% CI: −8.77 to −5.35) versus placebo. Relative to alternative beta-blockers, nebivolol demonstrated a superior probability of achieving target blood pressure (SBP <140 mmHg and DBP <90 mmHg) at doses of 2.5 mg (odds ratio [OR] = 4.14; 95% CI: 1.96–8.75) and 5 mg (OR = 1.15; 95% CI: 0.58–2.29). Additionally, nebivolol conferred a significant enhancement in erectile capability compared with metoprolol (an increase of 3.45 International Index of Erectile Function-5 points; 95% CI: 1.17–5.72). Safety evaluations confirmed that standard 5 mg dosing did not elevate adverse event rates compared with placebo (OR = 0.98; 95% CI: 0.77–1.26). Conclusion This comprehensive NMA establishes that nebivolol delivers significant SBP and DBP lowering compared with placebo, whilst outperforming traditional beta-blockers in overall blood pressure normalisation. Its proven efficacy in younger demographics, combined with a highly favourable impact on erectile function, reinforces nebivolol as an optimal therapeutic choice for managing hypertension across diverse patient groups.