Primary prevention in liver cirrhosis patients with esophageal varicesa: a systematic review and network meta-analysis

Objective: To compare the efficacy and safety of different primary preventive measures for esophageal variceal bleeding using a network meta-analysis. Methods: Randomized controlled trials (RCTs) on primary prevention were retrieved from PubMed, Cochrane Library, Embase, and Web of Science. Primary outcomes were the incidence of variceal bleeding, all-cause mortality, All-Cause Bleeding and Bleeding-Related Mortality. Secondary outcomes included adverse events and other decompensation events. Study quality was assessed with the Cochrane Risk of Bias tool. Data were analyzed using Revman 5.4 and Stata 16.0. Results: A total of 50 RCTs (6510 patients) evaluating 16 interventions were included. For reducing bleeding incidence, the combinations Midodrine + Propranolol (Mido+PPL), Carvedilol + Endoscopic Variceal Band Ligation (Carv+EVBL), and Fuzheng Huayu Capsule + Propranolol (FZHYJN+PPL) were superior. For lower all-cause mortality, Carv+EVBL, Mido+PPL, and Nadolol + Isosorbide Mononitrate (Nado+ISMN) were favorable. Carv+EVBL, EVBL, and Endoscopic Injection Sclerotherapy (EIS) were better for reducing bleeding-related mortality. Regarding safety, Mido+PPL, Nadolol (Nado), and Carvedilol (Carv) had fewer general adverse events, while Isosorbide Mononitrate (ISMN), Mido+PPL, and Carv had lower rates of other decompensation events. Conclusion: Based on low-certainty evidence, Mido+PPL demonstrated a favorable balance of efficacy and safety and is recommended as a preferred option. Mido+PPL, Carv+EVBL, and FZHYJN+PPL are recommended for primary prophylaxis in cirrhosis. For Child-Pugh A/B patients, Mido+PPL, Carv+EVBL, and FZHYJN+PPL are suggested, with EVBL as an alternative for those intolerant to drugs. EVBL may be considered for Child-Pugh C patients. Mido+PPL is recommended for prophylaxis within one year, FZHYJN+PPL for up to two years, and Carvedilol (alone or with EVBL) for long-term management beyond two years. Carvedilol and Propranolol showed superior net clinical benefit over Nadolol and Timolol. Although Nadolol (alone or with ISMN) may reduce mortality, its higher adverse event rate precludes it as a first-line strategy. FZHYJN, while effective, may increase the risk of other decompensation events.