S2359 Beyond Varices: The Cardiovascular Impact of Non-Selective Beta-Blockers in Cirrhosis

Introduction: Patients with cirrhosis and portal hypertension are at elevated cardiovascular risk due to systemic inflammation, autonomic imbalance, and hemodynamic alterations. Non-selective beta-blockers (NSBBs), routinely used to prevent variceal bleeding, may also influence cardiovascular outcomes. Methods: We conducted a systematic review and meta-analysis using the PRISMA guidelines. Literature searches were performed across PubMed, Embase, and Cochrane Library through February 2025 for studies assessing cardiovascular outcomes in adults with cirrhosis and clinically significant portal hypertension on long-term NSBB therapy (propranolol, nadolol, or carvedilol) versus no NSBBs. The primary outcome was major adverse cardiovascular events (MACE: myocardial infarction, stroke, cardiovascular death). Secondary outcomes included all-cause mortality and heart failure hospitalization. Ten eligible studies (N = 18,612 patients), including 2 randomized controlled trials and 8 observational cohorts, were included. Data were pooled using a random-effects model, and heterogeneity was quantified using the I² statistic. The risk of bias was assessed using the Newcastle–Ottawa Scale for cohorts and the Cochrane Risk of Bias 2 tool for RCTs. Results: Pooled analysis showed that NSBB use was associated with a statistically significant reduction in MACE (RR = 0.79, 95% CI: 0.68–0.91; P = 0.001; I² = 41%) and all-cause mortality (RR = 0.83,95% CI: 0.74–0.94; P = 0.004; I² = 52%). No significant difference was observed in heart failure hospitalizations (RR = 1.06, 95% CI: 0.89–1.26; P = 0.51; I² = 35%). Subgroup analyses by age, MELD score, and diabetes status confirmed the cardioprotective trend. Sensitivity analyses and leave-one-out tests confirmed robustness. Funnel plot and Egger's test showed minimal publication bias. Conclusion: Our meta-analysis provides pooled evidence supporting the cardiovascular benefit of NSBBs in patients with cirrhosis and portal hypertension. NSBBs are associated with a lower risk of MACE and mortality without increasing heart failure admissions. These findings suggest that NSBBs may serve a dual protective role—reducing both portal pressures and cardiovascular burden. While RCTs strengthen the conclusions, larger prospective trials remain necessary to confirm causality and guide practice.