Safety of long-term use of potassium-competitive acid blockers: a narrative review

Introduction Potassium-competitive acid blockers (P-CABs) reversibly inhibit gastric H + /K + -ATPase, providing rapid and potent acid suppression. They are increasingly used for gastroesophageal reflux disease, peptic ulcer disease, and Helicobacter pylori eradication. As maintenance therapy expands, long-term safety has drawn growing attention. Objective To evaluate the available evidence on the long-term safety of P-CABs, distinguishing established findings from potential safety signals. Methods This narrative review drew on searches of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov through 30 June 2026. Studies with at least 24 weeks of treatment or follow-up formed the longer-term human evidence base. Evidence was synthesized by safety outcome, considering the specific agent and study design. Conclusion Available comparative evidence, predominantly for vonoprazan, has not shown a substantially higher overall adverse event incidence than with proton pump inhibitors (PPIs). Sustained acid suppression can induce hypergastrinemia, which may be accompanied by parietal-cell hyperplasia, fundic gland dilatation, and other endoscopic mucosal changes. Evidence remains insufficient to determine the risks of rare or long-latency outcomes or to generalize long-term findings to all P-CABs. Long-term prescribing should include periodic reassessment of the indication and individualized monitoring.