Background: To assess the effects of combination therapies (endoscopic plus drug[s], drug combinations) on variceal/any-cause rebleeding and mortality among cirrhotic patients with one previous episode of variceal hemorrhage.

Summary: We searched PubMed, Embase, Cochrane Library, and Web of Science for eligible studies. We included 26 randomized controlled trials involving 2,536 adults using OR to measure the effects. Endoscopic variceal ligation (EVL) plus nadolol ranked first for reducing recurrent bleeds. Both EVL + nadolol and EVL + drugs (nadolol, sucralfate) decreased the risk of any-cause rebleeding than EVL alone (OR 0.34, 95% CI 0.12-0.97; OR 0.40, 95% CI 0.18-0.88, respectively). Meanwhile, EVL + drugs ranked first lowering mortality rates (P-score >0.85) with a marginal superiority over EVL alone (OR 0.52, 95% CI 0.26-1.01). Beta-blockers with isosorbide mononitrate (ISMN) also reached a marginal superiority (OR 0.78, 95% CI 0.56-1.09) for improving mortality. Key Messages: Our findings indicated that EVL + nadolol might be the preferred choice to cirrhotic patients with one previous episode of variceal hemorrhage for preventing rebleeding. EVL + nadolol + sucralfate and beta-blockers + ISMN may be potential alternatives to improve mortality. Further, well-controlled studies are warranted to compare the promising combination therapies.

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