P-CAB - amoxicillin dual therapy for H. pylori eradication: a narrative review of efficacy, safety, and guideline positioning.

Abstract

Background: Eradication rates of clarithromycin-based standard triple therapy have fallen below 80% in many regions, where primary clarithromycin resistance exceeds 30%. Bismuth-containing quadruple therapy (BQT) and concomitant therapy are limited by regimen complexity, high adverse event rates, and reduced adherence. Potassium-competitive acid blockers (P-CABs) provide rapid, potent acid suppression that is less affected by CYP2C19 polymorphisms than that achieved with PPIs, potentially enhancing the pH-dependent activity of amoxicillin.

Main text: Several randomized controlled trials and meta-analyses, largely based on East Asian cohorts, report eradication rates with P-CAB-amoxicillin dual therapy that are non-inferior or superior to BQT. In a network meta-analysis of 25 randomized controlled trials (7,605 patients), P-CAB-amoxicillin dual therapy achieved a pooled ITT eradication rate of 85.2% (95% CI, 83.7-86.7%) and ranked first for combined efficacy and safety (SUCRA, 92.7%). Compared with BQT, it was associated with fewer adverse events (OR, 0.32; 95% CI, 0.28-0.38) and higher compliance (OR, 1.49; 95% CI, 1.26-1.76). The 2024 ACG guideline conditionally suggests vonoprazan-amoxicillin dual therapy as an alternative first-line option, while BQT remains preferred. Maastricht VI/Florence similarly positions P-CAB-amoxicillin dual therapy as an alternative regimen. The 2025 revised Korean guidelines recognize P-CABs as alternatives to PPIs in antibiotic-containing eradication regimens but do not recommend P-CAB-amoxicillin dual therapy as a first-line regimen.

Conclusions: P-CAB-amoxicillin dual therapy is a promising, antibiotic-sparing candidate for H. pylori eradication, with efficacy comparable to BQT and a potentially lower adverse-event burden. Comparative evidence against concomitant therapy remains limited. Dedicated regional RCTs are needed before incorporation into national guidelines.