Comparison of Efficacy on First-Line Helicobacter Pylori Eradication Between Potassium-Competitive Acid Blocker (P-CAB)-Based Therapies Versus Proton-Pump Inhibitor (PPI)-Based Therapies

Background: Helicobacter pylori ( H. pylori ) is a gram-negative bacterium that infects over half of the world population, accountable for 89% of all gastric cancer cases. The efficacy of the proton-pump inhibitor (PPI) based-triple therapy is declining, while the novel potassium-competitive acid blocker (P-CAB) based therapy gets new attention. However, it remains unclear regarding the optimal duration and number of comedication(s) for P-CAB-based regimens, which P-CAB is the best-in-class, and whether P-CABs perform better than all PPIs. Objective: To compare the efficacy on first-line H. pylori eradication between P-CAB-based therapies versus PPI-based therapies. Methods: A systematic review on randomized controlled trials, with network meta-analysis conducted under the Frequentist approach. The P -score method was used to rank the probability of being the best intervention. Results: For the first-line treatment eradicating H. pylori infection, the 7-day vonoprazan-based triple therapy (VAC7) has the highest P -score for the probability of being the best intervention (0.96). VAC7 has a significantly higher eradication rate of H. pylori than most PPI-based therapies, including esomeprazole-based, lansoprazole-based, pantoprazole-based, and omeprazole-based regimens, as well as the other P-CAB based regimens, such as tegroprazan-based triple regimen (OR: 2.41, 95% CI: 1.13-5.15). Conclusion: Vonoprazan-based triple therapy has a higher eradication rate than PPI-based triple therapies, as well as other P-CABs based regimens. It remains unclear whether VAC7 is superior over vonoprazan-based dual therapy (VA7). Overall, VAC7 should be recommended for clinical and public health interventions, with VA7 as a possible alternative considering the local antimicrobial resistance profiles.