Comparative efficacy and safety of vonoprazan-based dual therapy vs. bismuth-based quadruple therapy for Helicobacter pylori eradication: a GRADE-assessed systematic review and meta-analysis with trial sequential analysis

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• Picked for Microbiology (medical) (top studies of the week, 13 September 2026): Helicobacter pylori eradication meta‑analysis

Abstract

BACKGROUND: Helicobacter pylori infects approximately 4. 4 billion individuals worldwide, causing chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma. The 2024 ACG guideline recommends bismuth-based quadruple therapy (BQT) as first-line treatment when susceptibility is unknown, while vonoprazan-amoxicillin (VA) dual therapy is conditionally endorsed as an alternative. Prior meta-analyses included vonoprazan-containing BQT control arms, introducing heterogeneity that may influence comparative efficacy estimates. This analysis addresses that gap by restricting the comparator to conventional PPI-based BQT. METHODS: A systematic search of PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, Google Scholar, and the Cochrane Library was conducted through April 2026 (PROSPERO: CRD420251108849) for randomized controlled trials (RCTs). All comparator arms were restricted to conventional PPI-based BQT. Outcomes included eradication rate, total adverse events (AE), nausea, diarrhea, treatment compliance, and bitter taste. Certainty of evidence was assessed using the GRADE approach and trial sequential analysis. Meta-analysis was performed using R software. RESULTS: From 17,661 screened articles, 15 RCTs comprising 4,410 patients were included. Pooled eradication rates were 86.4% with VA and 85.0% with BQT, with no statistically significant difference (RR 1.03, 95% CI 1.00-1.07; p = 0.05; I 2 = 46.1%). VA significantly reduced total AEs (17.1% vs. 35.4%; RR 0.48, 95% CI 0.42-0.54; p < 0.01; I 2 = 0.0%), nausea (4.4% vs. 10.6%; RR 0.44, 95% CI 0.32-0.59; p < 0.01; I 2 = 26.7%), and bitter taste (5.6% vs. 14.5%; RR 0.10, 95% CI 0.06-0.18; p < 0.01; I 2 = 43.2%). No significant differences were observed for diarrhea or compliance. GRADE certainty was moderate for eradication, low for AEs, nausea, and bitter taste, and very low to low for diarrhea and compliance. Trial sequential analysis confirmed sufficient evidence for reductions in AEs, nausea, and bitter taste, while eradication, diarrhea, and compliance remained inconclusive. CONCLUSION: VA dual therapy achieves eradication rates comparable to PPI-based BQT while offering a significantly more favorable tolerability profile, driven by fewer total AEs, less nausea, and less bitter taste. As all included trials were conducted in China, generalizability requires further investigation. These findings support VA dual therapy as a viable alternative for first-line H. pylori management.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1108849, identifier: CRD420251108849.

Abstract as published, via PubMed.