Work

Effect of omeprazole on platelet reactivity in patients with diabetes mellitus and coronary artery disease receiving aspirin and clopidogrel: a randomised, placebo-controlled crossover trial (POC-DM)

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Background Proton pump inhibitors are often prescribed with aspirin and clopidogrel to reduce gastrointestinal bleeding risk. However, the European Society of Cardiology diabetes guidelines recommend avoiding concomitant use of omeprazole and clopidogrel due to potential drug–drug interactions. Evidence in patients with diabetes mellitus (DM), who have a higher prevalence of high on-treatment platelet reactivity, remains limited. In Thailand, where omeprazole is the only reimbursed PPI, this potential interaction has important clinical implications. We aimed to evaluate the effect of omeprazole on platelet reactivity, measured as P2Y12 reaction units (PRU), in patients with DM and coronary artery disease (CAD) receiving aspirin and clopidogrel.Methods This double-blind, randomised, placebo-controlled crossover trial enrolled patients with DM and CAD receiving aspirin 81 mg/day and clopidogrel 75 mg/day. Participants received omeprazole 20 mg or a matching placebo for 2 weeks, followed by crossover to the alternate treatment. Platelet reactivity was assessed using the VerifyNow P2Y12 assay. The primary outcome was the change in PRU following omeprazole coadministration compared with both baseline and placebo. Secondary outcomes included changes in clopidogrel responder status (PRU >208) before and after omeprazole treatment and PRU values in each treatment period.Results 50 patients were enrolled (median age 67 years; 58% male). Omeprazole significantly increased PRU by a mean difference of 20.57 units versus baseline (p=0.002) and 16.14 units versus placebo (p=0.006). The proportion of clopidogrel non-responders increased from 44% to 56%, with 25% of baseline responders converting to non-responders.Conclusions Omeprazole significantly attenuated clopidogrel’s antiplatelet effect in patients with diabetes and CAD. Concomitant use may be avoided, especially in those with high thrombotic risk.Trial registration number TCTR20260714003.

Source: Open Heart

DOI: 10.1136/openhrt-2026-004409