Beyond Proton Pump Inhibitors: Vonoprazan as a New Standard in Helicobacter pylori Eradication

Abstract

Helicobacter pylori remains a significant global health burden, driving chronic gastritis, peptic ulcer disease, and gastric cancer. Conventional proton pump inhibitor (PPI)-based eradication therapies have shown declining efficacy due to rising antimicrobial resistance, variable acid suppression, and adherence challenges. Vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), offers rapid, potent, and sustained acid inhibition independent of meal timing or CYP2C19 metabolism. Clinical trials and meta-analyses demonstrate superior or non-inferior eradication rates compared to PPI-based regimens, particularly in clarithromycin-resistant infections, with favourable safety and tolerability profiles. Real-world studies support its effectiveness, adherence benefits, and cost-effectiveness across healthcare systems. Vonoprazan-based dual, triple, and quadruple therapies are increasingly integrated into regional and international guidelines, with fixed-dose formulations and paediatric programmes under development. Future directions include broader global access, long-term safety monitoring, and exploration of novel delivery platforms. Overall, vonoprazan represents a paradigm shift in H. pylori management, providing a reliable alternative to PPIs and addressing key limitations of current eradication strategies.