Vonoprazan–amoxicillin dual therapy improves 14-day eradication and reduces adverse events in patients with Helicobacter pylori infection: an updated landmark systematic review and meta-analysis of 11 randomized trials with subgroup analysis

Urvashi Bharia; Anika Goel; FNU Raja; Gowrishankar Palaniswamy; Krishna Sangeetha Gadde; Erine Joseph; Ishita Gupta; Sharath Udaya Kumar; Isha Piyushkumar Shah; Anika Chowdhury; Homi Patel; Kaival Malav Shah; Venkata Dileep Kumar Veldi; Ashesh Das

Authors Urvashi Bharia, Anika Goel, FNU Raja, Gowrishankar Palaniswamy, Krishna Sangeetha Gadde, Erine Joseph, Ishita Gupta, Sharath Udaya Kumar, Isha Piyushkumar Shah, Anika Chowdhury, Homi Patel, Kaival Malav Shah, Venkata Dileep Kumar Veldi, Ashesh Das.

Abstract

Background Vonoprazan, a potassium-competitive acid blocker (P-CAB), may enhance Helicobacter pylori (H. pylori) eradication in combination with amoxicillin. With increasing drug resistance, dual therapy is a potential alternative to standard triple and quadruple regimens. This systematic review and meta-analysis evaluated the efficacy and safety of vonoprazan dual therapy (VDT) as first-line treatment for H. pylori infection.

Methods A comprehensive systematic search on PubMed, Embase, Scopus and Cochrane Library identified 11 randomized controlled trials (RCTs) involving 2877 patients (1439 VDT; 1438 control), comparing VDT with standard triple therapy, quadruple therapy or individualized treatment regimens for H. pylori eradication, up to March 2025. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method for dichotomous outcomes. Random or fixed-effects models were applied based on heterogeneity, assessed using the Higgins I2 statistic. A P-value <0.05 was considered statistically significant.

Results VDT significantly improved eradication rates compared to standard therapy (RR 1.06, 95%CI 1.00-1.12; P<0.001), driven primarily by 14-day regimens (RR 1.08, 95%CI 1.01-1.15; P=0.0001); no benefit was seen for 7-day regimens (RR 0.97, 95%CI 0.91-1.04; P=0.30), with low heterogeneity (8.6%). There was no significant difference in drug compliance (RR 1.02, 95%CI 0.99-1.05; P=0.03), with moderate heterogeneity (50.3%). VDT demonstrated significantly fewer adverse events (RR 0.66, 95%CI 0.52-0.84; P<0.001).

Conclusions VDT is as effective as standard therapies overall, but shows clear superiority in 14-day regimens, with no advantage in 7-day durations. The observed heterogeneity was probably due to differences in treatment duration and regional variability in resistance.

Keywords Helicobacter pylori, vonoprazan, dual therapy, triple therapy, amoxicillin

Ann Gastroenterol 2026; 39 (3): 294-302