SynthesisEuropean journal of clinical pharmacology2026
Efficacy and safety of zilebesiran in adults with hypertension: a systematic review and meta-analysis of randomized controlled trials.
Synthesis in European journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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10 authors.
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Abstract
backgroundHypertension is a major modifiable risk factor for cardiovascular disease, yet global control rates remain low. Zilebesiran, an investigational RNA interference therapy, targets angiotensinogen to modulate the renin-angiotensin-aldosterone system. While previous reviews exist, updated evidence is needed to better characterize its efficacy and safety.
methodsA systematic search of PubMed, Cochrane Library, Google Scholar, Embase, and ClinicalTrials.gov was conducted using MeSH and free-text terms. Two reviewers independently extracted data and assessed risk of bias using RoB 2.0. A random-effects model was applied in RevMan 5.4, with heterogeneity evaluated using I² statistics.
resultsFour studies involving 1,412 adults with mild to moderate hypertension were included. The primary outcome, placebo-adjusted change in office systolic blood pressure (SBP), showed a pooled mean difference (MD) of -7.16 mmHg (95% CI: -13.63 to -0.70). Secondary outcomes demonstrated significant reductions in 24-hour ambulatory SBP (MD: -9.92 mmHg; 95% CI: -18.74 to -1.10), daytime SBP (MD: -9.76 mmHg; 95% CI: -19.46 to -0.06), nighttime SBP (MD: -9.95 mmHg; 95% CI: -16.71 to -3.19), and 24-hour ambulatory diastolic blood pressure (DBP) (MD: -7.27 mmHg; 95% CI: -11.13 to -3.41). In subgroup analysis by follow-up duration, the reduction in daytime SBP was significantly greater at 3 months than at 6 months (P = 0.02), suggesting a potential attenuation of the antihypertensive effect over time. Zilebesiran markedly reduced angiotensinogen levels (MD: -1.00; 95% CI: -1.15 to -0.85). Overall adverse events were significantly more frequent with Zilebesiran compared with placebo (OR: 1.46), including increased risks of hyperkalemia and injection-site reactions, while serious adverse events did not differ significantly between groups.
conclusionOverall, zilebesiran produced significant and consistent BP reductions, especially in ambulatory measures, with a favorable safety profile. However, evidence remains limited by small sample sizes and reliance on placebo comparators, and larger trials with active antihypertensive controls are needed to validate long-term efficacy and safety.
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