Network meta-analysis compares preventive measures for esophageal variceal bleeding in 6510 cirrhosis patients.

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Frontiers in Medicine Published April 16, 2026 Medically reviewed April 25, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Interpret network meta-analysis findings cautiously due to low-certainty evidence when selecting prophylaxis for variceal bleeding.

This publication is a network meta-analysis evaluating primary preventive measures for esophageal variceal bleeding in patients with liver cirrhosis. The review synthesized data from a total population of 6510 patients across various interventions, including beta-blockers, endoscopic procedures, and combination therapies. The scope encompasses incidence of variceal bleeding, all-cause mortality, and bleeding-related mortality as primary outcomes, alongside adverse events and other decompensation events.

Regarding bleeding incidence, midodrine plus propranolol, carvedilol plus endoscopic variceal band ligation, and fuzheng huayu capsule plus propranolol were identified as superior. For all-cause mortality, carvedilol plus endoscopic variceal band ligation, midodrine plus propranolol, and nadolol plus isosorbide mononitrate demonstrated favorable results. Bleeding-related mortality outcomes favored carvedilol plus endoscopic variceal band ligation, endoscopic variceal band ligation alone, and endoscopic injection sclerotherapy.

Safety profiles varied among interventions. Midodrine plus propranolol, nadolol, and carvedilol were associated with fewer general adverse events. Isosorbide mononitrate, midodrine plus propranolol, and carvedilol showed lower rates of other decompensation events. Conversely, fuzheng huayu capsule may increase the risk of other decompensation events. The authors explicitly state the evidence is based on low-certainty evidence, which limits the strength of these conclusions.

Practice relevance suggests midodrine plus propranolol demonstrated a favorable balance of efficacy and safety and is recommended as a preferred option. Other combinations are recommended for primary prophylaxis in cirrhosis. However, specific recommendations for Child-Pugh A, B, and C patients and timing recommendations were noted without detailed data in this summary. Clinicians should interpret these findings within the context of the acknowledged low-certainty evidence.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

ObjectiveTo compare the efficacy and safety of different primary preventive measures for esophageal variceal bleeding using a network meta-analysis.MethodsRandomized 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.ResultsA 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.ConclusionBased 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.