Eradication of Helicobacter pylori With Vonoprazan–Amoxicillin Dual Therapy as an Alternative for Bismuth-Based Quadruple Therapy: A Systematic Review and Noninferiority Meta-Analysis

Introduction: Whether the efficacy of vonoprazan–amoxicillin dual therapy (VADT) for Helicobacter pylori eradication is clinically acceptable compared with guideline-recommended bismuth-based quadruple therapy (BQT) remains uncertain. Prior analyses have largely relied on superiority frameworks. Methods: PubMed, EMBASE, and CENTRAL were searched through December 23, 2025, for randomized controlled trials (RCTs) comparing VADT with BQT for H. pylori eradication. Intention-to-treat and per-protocol eradication were summarized through Bayesian meta-analysis as absolute risk differences. Noninferiority margins were prespecified at −10%, −5%, and 0% (superiority). Adverse events (AEs) were evaluated as secondary outcomes. Evidence certainty was assessed using GRADE. Results: Eighteen Asian RCTs (5866 participants) were included. In intention-to-treat analyses, VADT achieved an absolute eradication increase of +2.27% compared with BQT (95% credible interval [CrI] −1.34% to +5.71%). The posterior probability of noninferiority exceeded 99% for the −10% and −5% margins but declined to 90.41% at 0%. In per-protocol analyses, eradication showed an absolute decrease of 0.28% (95% CrI −3.30% to +4.17%), with noninferiority probabilities exceeding 99% for the −10% and −5% margins, but declining to 56.43% at 0%. VADT was associated with significantly lower rates of dysgeusia, dizziness/headache, nausea/vomiting, and overall mild AEs. Evidence certainty was moderate for intention-to-treat noninferiority in Eastern populations and low or very low for all other Eastern and Western analyses. Discussion: VADT may be a reasonable alternative in East Asian settings where tolerability or regimen simplicity is a priority, but evidence is insufficient to support generalization to Western or non-Asian populations. © 2026 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.