Statin Therapy and Portal Pressure Reduction in Cirrhosis: A Systematic Review and Meta‐Analysis

ABSTRACT Background and Aims Portal hypertension is the principal driver of cirrhosis decompensation, leading to heightened morbidity and mortality. While non‐selective beta‐blockers (NSBBs) remain the standard of care, up to 45% of patients fail to achieve sufficient portal pressure reduction. Statins have gained attention as a potential therapeutic agent for portal hypertension. We conducted a systematic review and meta‐analysis of randomised controlled trials (RCTs) to evaluate the impact of statins on portal pressure and cirrhosis‐related outcomes. Methods We searched five databases through November 2024 for RCTs evaluating statin therapy in adults with cirrhosis and clinically significant portal hypertension (CSPH). The primary outcome was HVPG reduction, assessed as an absolute decrease or the proportion achieving a haemodynamic response (HVPG reduction ≥ 20% from baseline or to ≤ 12 mmHg). Secondary outcomes included variceal bleeding, ascites and mortality. Random‐effects meta‐analyses were performed using pooled mean differences (MDs) and risk differences (RDs) with 95% confidence intervals (CIs). Results Six RCTs ( n = 492) were included. Statin therapy was associated with significant HVPG reduction (MD: 1.1 mmHg; 95% CI: 0.44–1.77; I 2 = 38.7%) and higher hemodynamic response (RD: 0.24; 95% CI: 0.02–0.45; I 2 = 76.8%). No significant differences were seen in variceal bleeding, ascites or mortality. On subgroup analysis, HVPG benefit was limited to studies with short‐term follow‐up. In studies comparing statin plus NSBB to NSBB alone, the addition of statins further reduced HVPG. Conclusions Statins modestly lower HVPG in cirrhosis‐related portal hypertension and may be a useful adjunct to NSBBs. Larger trials are needed to assess long‐term clinical benefits. Trial Registration PROSPERO registration number: CRD42025622478