Low-dose versus high-dose amoxicillin in vonoprazan-based dual therapy for Helicobacter pylori eradication: a systematic review and meta-analysis

Background Vonoprazan-based dual therapy with high dose amoxicillin is comparable to or even better than bismuth quadruple therapy (BQT). It is uncertain whether low-dose amoxicillin can be used instead of high-dose amoxicillin. We conducted a systematic review and meta-analysis to compare the efficacy, safety and compliance in vonoprazan dual therapy with low or high dose amoxicillin. Methods A comprehensive search of the literature from the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to December 15, 2024. Trials comparing H. pylori eradication rates and adverse events between vonoprazan-amoxicillin with a low-dose amoxicillin regimen (L-VA) and a high-dose amoxicillin regimen (H-VA) were included. Data were pooled using fixed- or random-effects models and expressed as relative risk (RR) with corresponding 95% confidence interval (CI). Results Seven randomized controlled trials (RCTs) with 1688 patients were included. The H-VA dual therapy showed superior H. pylori eradication rates compared to the L-VA dual therapy (intention-to-treat [ITT]: 84.0% vs. 79.8%; RR=1.05, 95%CI 1.00-1.09; P=0.03; per-protocol [PP]: 89.4% vs. 85.0%; RR=1.06; 95%CI 1.02-1.09; P=0.001). Subgroup analysis by treatment duration showed no significant difference in eradication rates between the H-VA and L-VA groups for 7-day therapy (67.0% vs. 60.2%; RR=1.13; 95%CI 0.92-1.38; P=0.24), 10-day therapy (87.7% vs. 81.7%; RR=1.06; 95%CI 0.97-1.16; P=0.17), and 14-day therapy (85.3% vs. 83.2%; RR=1.02; 95%CI 0.96-1.08; P=0.50) in the ITT analysis. In the PP analysis, the H-VA group had significantly higher eradication rates compared to the L-VA group over 14 days (93.9% vs. 89.9%; RR=1.04; 95%CI 1.00-1.09; P=0.04; I²=0%). The subgroup analysis for 7-day (68.3% vs. 67.7%; RR=1.02; 95%CI 0.85-1.23; P=0.81; I²=0%) and 10-day therapy (90.7% vs. 84.0%; RR=1.07; 95%CI 0.98-1.16; P=0.11; I²=44%) revealed no significant differences. The incidence of adverse events and treatment compliance were similar between the two groups. Conclusion The H-VA dual therapy demonstrated superior efficacy compared to L-VA therapy in the treatment of H. pylori infection. A 14-day course of H-VA was associated with higher eradication rates when compared to L-VA. Safety and compliance were comparable between the two treatment groups.