Impact of adding statins to non-selective beta-blockers in cirrhosis with portal hypertension: a systematic review and meta-analysis of randomized controlled trials

Introduction and Objectives Despite non-selective beta-blockers (NSBBs), patients with cirrhosis and portal hypertension (PH) remain at substantial risk of death. Statins may improve intrahepatic microcirculation and potentially complement NSBB effects. Materials and Methods We searched PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov from inception to October 2025 for randomized controlled trials (RCTs) comparing NSBB-based therapy plus statins versus NSBB-based therapy alone. Rare events were synthesized using fixed-effect Peto odds ratios; other outcomes were pooled with random-effects models, with prediction intervals (PI) reported. Prespecified subgroup and sensitivity analyses were performed. Results Seven RCTs ( n = 954) were included. Statin add-on therapy was not clearly associated with fewer PH-related complications, including variceal bleeding (RR = 0.79, P = 0.10), new or worsening ascites (RR = 0.81, P = 0.13), or hepatic encephalopathy (RR = 0.41, P = 0.06). However, it was associated with a lower risk of all-cause mortality (RR = 0.46, 95% CI: 0.32–0.65, 95% PI: 0.28–0.76, P < 0.001, I2 = 0). Adding statins also resulted in greater hepatic venous pressure gradient (HVPG) reductions and a higher proportion of patients achieving a ≥ 20% HVPG decrease. Aches and transaminase elevations occurred more often with statins. In subgroup analyses, the mortality association was observed in Child-Pugh A/B patients. Conclusions In cirrhosis with PH, statin add-on therapy is associated with improved portal hemodynamics and lower all-cause mortality, whereas associations with PH-related complications remain uncertain. PROSPERO registration number CRD420251172719