Impact of Renin-Angiotensin-Aldosterone System Inhibitors on Liver-Related Events and Mortality in Patients With Cirrhosis: A Meta-Analysis of Real-World Evidence.

[BACKGROUND] The therapeutic implications of renin-angiotensin-aldosterone system inhibitors (RAASi) in modulating liver-related events (LREs) and mortality among patients with cirrhosis remain clinically uncertain. This meta-analysis synthesizes real-world evidence to clarify the association between RAASi use and clinical outcomes in this population.

[METHODS] We conducted a systematic literature search across PubMed, Embase, and Web of Science through December 25, 2024. Studies comparing LREs incidence or overall survival (OS) between patients with cirrhosis receiving RAASi versus non-users were eligible. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were calculated to obtain an overall estimate.

[RESULTS] Seven studies comprising nine cohorts (N = 22 736) met inclusion criteria. RAASi use demonstrated a modest but significant reduction in LREs risk (HR, 0.81; 95% CI, 0.66-1.00; p = 0.0493) and significantly improved OS (HR, 0.73; 95% CI, 0.66-0.81; p < 0.0001). Subgroup analysis revealed particular benefit in hepatocellular carcinoma (HCC) prevention (HR, 0.88; 95% CI, 0.78-0.99; p = 0.0306).

[CONCLUSION] This meta-analysis suggests RAASi therapy may confer dual hepatoprotective and survival benefits in patients with cirrhosis, particularly regarding HCC prevention. While real-world evidence indicates favorable risk reduction profiles, these findings warrant validation through prospective randomized trials to establish causality and optimize therapeutic protocols. Clinicians should consider individualized risk-benefit assessments when prescribing RAASi in this vulnerable population.