Pooling nine studies and 34,123 adults on single or dual antiplatelet therapy, potassium-competitive acid blockers (P-CABs) did not differ from proton pump inhibitors in gastrointestinal bleeding (RR 0.89, 95% CI 0.67-1.18). P-CAB users had fewer major adverse cardiovascular events (RR 0.80, 0.65-0.98) and less revascularisation (RR 0.77, 0.59-0.99), but only in observational data. Mortality, myocardial infarction, stroke and platelet reactivity showed no difference. Only one study was randomised.
The interesting hypothesis is pharmacological: omeprazole and esomeprazole inhibit CYP2C19, the enzyme that activates clopidogrel, while P-CABs such as vonoprazan are cleared mainly via CYP3A4. Yet platelet reactivity did not differ here, which undercuts the proposed mechanism for any cardiovascular edge. Those MACE signals more plausibly reflect confounding by indication, regional prescribing patterns (most P-CAB data come from East Asia) and differing acid-suppressant co-therapy, which the authors acknowledge. The confidence intervals on bleeding are also wide enough to hide a meaningful difference in either direction, so equivalence is not shown. Editorially, this is confirmatory and hypothesis-generating, not practice-changing: PPIs remain the evidence-based default for gastroprotection, and pantoprazole is already a common choice to sidestep the clopidogrel interaction. Anyone taking aspirin or clopidogrel long term should not switch or stop acid suppression on this basis; the question worth raising with a doctor is which gastroprotective agent suits their specific antiplatelet. Adequately powered randomised trials with cardiovascular endpoints are needed before P-CABs displace PPIs.