Introduction Hypertension remains a significant global health concern and a leading risk factor for cardiovascular disease. Zilebesiran, an investigational RNA interference therapeutic, aims to reduce blood pressure by targeting the hepatic production of angiotensinogen, a key precursor in the renin-angiotensin-aldosterone system. This systematic review and Bayesian meta-analysis was conducted to evaluate the antihypertensive efficacy of Zilebesiran, specifically its effect on 24-hour systolic blood pressure (SBP) in patients with hypertension. Methods A systematic search of PubMed, Cochrane Library, and other relevant databases was performed to identify randomized controlled trials comparing Zilebesiran to placebo in patients with primary hypertension. Studies were selected based on their reporting of the mean change in 24-hour SBP at 3 months. A Bayesian approach was used to assess the pooled treatment effect and quantify the uncertainty in the results, incorporating credible intervals for the treatment effect estimates. Results Three studies involving 1,145 patients were included in the analysis. Zilebesiran demonstrated a statistically significant reduction in 24-hour SBP compared to placebo. The pooled mean difference (MD) for the change in 24-hour SBP was -12.84 mmHg (95% CI: -16.00 to -9.68), indicating a substantial antihypertensive effect. The results were consistent across the included studies, with low heterogeneity (I2 = 21.7%). Sensitivity analyses confirmed the robustness of the findings, and no evidence of publication bias was detected through visual inspection of the funnel plot. Conclusion This Bayesian meta-analysis provides robust evidence supporting the efficacy of Zilebesiran in reducing 24-hour SBP in patients with hypertension. The treatment demonstrated significant and consistent benefits across studies, with minimal heterogeneity observed. Zilebesiran represents a promising therapeutic option for the management of hypertension, particularly at doses between 250 mg and 500 mg. Further studies are needed to explore long-term outcomes and refine patient selection for optimal benefit.
Shahriar et al. (Wed,) studied this question.