Introduction
Potassium-competitive acid blockers (P-CABs) represent a novel class of gastric acid suppressants with distinct pharmacological properties compared to proton pump inhibitors (PPIs). Vonoprazan and tegoprazan, the most extensively studied P-CABs, have demonstrated rapid, potent, and sustained acid suppression independent of meal timing and CYP2C19 polymorphisms. Despite accumulating evidence from randomized controlled trials (RCTs), the comparative efficacy and safety of P-CABs versus PPIs across acid-related disorders remain incompletely synthesized.
Aims & Methods
We conducted an umbrella review from meta-analyses and systematic reviews comparing P-CABs with PPIs for the treatment of Helicobacter pylori infection, gastroesophageal reflux disease (GERD), erosive esophagitis (EE), and peptic ulcer disease (PUD), with particular attention to efficacy stratified by clarithromycin susceptibility, mucosal healing at 4 and 8 weeks, symptom resolution, and safety outcomes including hypergastrinemia and hepatotoxicity. We searched multiple databases and extracted pooled effect estimates, absolute rates, confidence intervals, and GRADE assessments, where reported.
Results
We identified 30 high-quality systematic reviews and meta-analyses. For H. pylori eradication, vonoprazan-based triple therapy demonstrated overall superiority over PPI-based regimens (RR 1.09, 95% CI 1.03–1.15; 13 RCTs) , driven predominantly by marked superiority in clarithromycin-resistant infections (eradication rate 74.9% vs 41.5%; RR 1.64, 95% CI 1.21–2.23) [1], while showing no advantage in clarithromycin-susceptible strains (92.5% vs 90.1%; RR 1.01, 95% CI 0.98–1.04) [1]. Network meta-analyses ranked 2-week vonoprazan-based triple therapy highest for eradication efficacy [2]. For erosive esophagitis, vonoprazan demonstrated healing rates of 91.7% (95% CI 86.8–94.8%) at 4 weeks and 88.5% (95% CI 69.7–96.2%) at 8 weeks in PPI-resistant GERD, with network meta-analysis showing superior healing versus rabeprazole (OR 3.94, 95% CrI 1.15–14.03) and numerical advantages versus other PPIs at 8 week. Meta-analyses of P-CABs in GERD reported pooled healing advantage (OR 1.67, 95% CI 1.24–2.24). Tegoprazan demonstrated noninferiority to PPIs at both 4 weeks (RR ~1.05, 95% CI 0.96–1.16) and 8 weeks (RR ~1.02, 95% CI 0.98–1.06). Vonoprazan significantly improved GERD symptom scores versus PPIs (MD −3.88, 95% CI −5.48 to −2.28; moderate GRADE evidence). Safety profiles were generally comparable, with no significant differences in overall adverse events or serious adverse events between P-CABs and PPIs [1,3]. One tegoprazan meta-analysis identified higher drug-related treatment-emergent adverse events (RR 1.23, 95% CI 1.03–1.48) .Pooled data on hypergastrinemia and liver enzyme elevations were not consistently reported across reviews.
Conclusion
P-CABs, particularly vonoprazan, demonstrate superior efficacy to PPIs for H. pylori eradication in clarithromycin-resistant infections and comparable or superior efficacy for erosive esophagitis healing, with generally similar safety profiles. Tegoprazan shows noninferiority for EE healing. The evidence base is predominantly Asian, and clarithromycin susceptibility testing should guide therapy selection. Future research should address geographic diversity, long-term safety outcomes, and cost-effectiveness in diverse populations.
References
[1]Chen, P. Y., Tsai, F. P., Chen, M. J., Yang, H. Y., Wu, M. S., & Liou, J. M. (2024). Vonoprazan-based versus proton pump inhibitor-based therapy in Helicobacter pylori eradication: an updated systematic review and meta-analysis of randomised trials. Gut, 73(5), 872–874. https://doi.org/10.1136/gutjnl-2023-329826
[2]Jung, Y. S., Kim, E. H., & Park, C. H. (2017). Systematic review with meta-analysis: the efficacy of vonoprazan-based triple therapy on Helicobacter pylori eradication. Alimentary pharmacology & therapeutics, 46(2), 106–114. https://doi.org/10.1111/apt.14130
[3] Ouyang, M., Zou, S., Cheng, Q., Shi, X., & Sun, M. (2024). Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers and Proton Pump Inhibitors for First-Line Helicobacter pylori Eradication Therapy: A Systematic Review and Network Meta-Analysis. Helicobacter, 29(6), e13150. https://doi.org/10.1111/hel.13150