Potassium-competitive acid blockers for erosive reflux disease and stress ulcer prophylaxis: a narrative review

Potassium-competitive acid blockers (P-CABs) are the first mechanistically distinct oral acid suppressants to challenge proton pump inhibitors (PPIs) in routine practice. By reversibly inhibiting gastric H+/K+-ATPase without requiring acid activation, they provide rapid onset of action, durable 24-hour acid control, and less dependence on meal timing and CYP2C19 variability. These pharmacologic features are clinically relevant in acid-related disorders, but the clinical evidence is not uniform across individual compounds. Within the class, the most mature efficacy and safety data are derived from vonoprazan, whereas newer agents, including zastaprazan, remain supported by a more limited evidence base. In erosive esophagitis, randomized trials indicate that P-CABs are effective acid suppressants, but compound-specific conclusions are more appropriate than broad assumptions of interchangeable class effects. For zastaprazan specifically, phase III data show that 20 mg is noninferior to esomeprazole 40 mg at week 8, with higher week-4 healing rates in a predominantly low-grade population. By contrast, no clinical trials have directly evaluated any P-CAB for stress ulcer prophylaxis in critically ill adults. Current intensive care unit guidelines continue to support PPIs or histamine-2 receptor antagonists for patients at high risk of stress-related gastrointestinal bleeding, and pantoprazole remains the best-established benchmark. This review integrates mechanistic, pharmacokinetic, efficacy, safety, regulatory, and guideline data relevant to P-CABs, with particular attention to zastaprazan, while distinguishing compound-specific findings from broader class-level considerations.