Potassium-competitive Acid Blockers in Gastroesophageal Reflux Disease and Functional Dyspepsia: A Korean Expert Review With Original Meta-analyses

Potassium-competitive acid blockers (P-CABs) have emerged as a potent alternative to proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease and functional dyspepsia (FD). This narrative review incorporating original meta-analyses summarizes the latest evidence from randomized controlled trials and meta-analyses, emphasizing the efficacy, safety, and clinical applications of P-CABs such as vonoprazan, tegoprazan, fexuprazan, keverprazan, and zastaprazan. P-CABs demonstrate rapid onset, sustained acid suppression, and superior healing rates in erosive esophagitis (EE), particularly in severe EE (grade C/D). Maintenance therapy in healed EE with P-CABs also yields higher endoscopic remission rates compared to PPIs. In non-erosive reflux disease, P-CABs offer rapid and sustained symptom control compared with placebo. Their pharmacologic profiles, including flexible dosing and rapid action, support on-demand therapy, potentially enhancing patient satisfaction. In addition, P-CABs may help overcome unmet needs from suboptimal efficacy of PPIs in nocturnal heartburn and extraesophageal symptoms. Emerging economic evaluation suggests P-CABs may be cost-effective in Asian healthcare systems. In FD, tegoprazan offers effective symptom relief without delaying gastric emptying, distinguishing it from PPIs. Limited clinical and real-world data indicate that second-generation P-CABs do not exhibit significant hepatotoxicity, however, long-term hypergastrinemia and mucosal changes warrant further surveillance. This review highlights the evolving role of P-CABs in gastroesophageal reflux disease and FD and emphasizes the need for further research to refine their clinical positioning, optimize therapeutic strategies, and evaluate long-term safety outcomes.