Meta-Analysis: Potassium-Competitive Acid Blockers Versus Proton Pump Inhibitors for Gastroprotection in Patients Receiving Antiplatelet Therapy.

BACKGROUND: PPIs are standard for gastroprotection during antiplatelet therapy. However, certain PPIs, chiefly omeprazole and esomeprazole, inhibit cytochrome P450 2C19 (CYP2C19), which activates clopidogrel, whereas potassium-competitive acid blockers (P-CABs) are metabolised predominantly by CYP3A4. AIMS: To compare the efficacy of P-CABs with PPIs in preventing gastrointestinal bleeding in adults receiving single or dual antiplatelet therapy. METHODS: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials from inception to 31st May 2026 for randomised and comparative observational studies of P-CABs versus PPIs. Risk ratios (RRs) and mean differences were pooled using random-effects models. The primary outcome was gastrointestinal bleeding; secondary outcomes included major adverse cardiovascular events (MACE), all-cause mortality, myocardial infarction, revascularisation, stroke, upper gastrointestinal bleeding and platelet reactivity. RESULTS: We included nine studies (one randomised, eight observational; 34,123 patients). Gastrointestinal bleeding did not differ between groups (RR 0.89, 95% CI 0.67-1.18). MACE (RR 0.80, 0.65-0.98); revascularisation (RR 0.77, 0.59-0.99) was less frequent with P-CABs (observational studies only). No differences were seen for all-cause mortality, myocardial infarction, stroke, or platelet reactivity. Findings may be confounded by study origin, ulcerogenic and acid-suppressive agents, and outcome definitions. CONCLUSIONS: P-CABs showed no statistically significant difference from PPIs in gastrointestinal bleeding. Lower rates of MACE and revascularisation were from observational studies. Therefore, these findings should be interpreted with caution, as they do not establish non-inferiority or a cardiovascular benefit. Randomised trials are needed to confirm these findings. TRIAL REGISTRATION: PROSPERO CRD420261372513 (International Prospective Register of Systematic Reviews).