Meta-Analysis: Potassium-Competitive Acid Blockers Versus Proton Pump Inhibitors for Gastroprotection in Patients Receiving Antiplatelet Therapy
In brief
Potassium blockers show no clear bleeding advantage over PPIs in antiplatelet users
Across nine studies involving 34,123 patients, potassium-competitive acid blockers and proton pump inhibitors had similar rates of gastrointestinal bleeding. Lower rates of major cardiovascular events and revascularisation with potassium blockers came only from observational studies, which may be confounded; the findings do not establish a cardiovascular benefit or prove the drugs are equivalent, so randomized trials are needed.
- Journal
- Alimentary pharmacology & therapeutics (Q1)
- Published
- 28 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Pedro Giavarini Mansk, Vanisha Kumar, Ana Maria T Fagundes, Erik E Chiong Espinoza, Román Rodríguez Milán, Nikita Patil, et al.
- PMID
- 42949291
- DOI
- 10.1111/apt.71078
Why clinicians should know about it
- Picked for Gastroenterology (top studies of the week, 1 November 2026): Comparative gastroprotection evidence for patients receiving antiplatelets
Abstract
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).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.