Notably, the PPI omeprazole has been reported to significantly decrease the inhibitory effect of clopidogrel on platelet aggregation.38,39 One study reported that the PPI pantoprazole was not associated with recurrent MI among patients receiving clopidogrel, possibly due to pantoprazole s lack of inhibition of CYP450 2C19.35 Other studies have examined the P2Y12 receptor inhibitor prescribed with the PPI. One open-label drug study evaluated the effects of the PPI lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy subjects given single doses of prasugrel 60 mg and clopidogrel 300 mg with and without concurrent lansoprazole 30 mg per day. The data suggest that inhibition of platelet aggregation was reduced in patients who took the combina- tion of clopidogrel and lansoprazole, whereas platelet aggre- gation was unaffected after a prasugrel dose.40 Another study36 assessed the association of PPIs with the pharmacodynamics and clinical efficacy of clopidogrel and prasugrel, based on populations from 2 randomized trials, the PRINCIPLE (Prasugrel In Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation) TIMI-44 trial41 and the TRITON TIMI 38 trial.7 The findings indi- cated that first, PPI treatment attenuated the pharmacody- namic effects of clopidogrel and, to a lesser extent, those of prasugrel. Second, PPI treatment did not affect the clinical outcome of patients given clopidogrel or prasugrel. This finding was true for all PPIs that were studied, including omeprazole and pantoprazole. Observational trials may be confounded by selection bias. In the COGENT (Clopidogrel and the Optimization of Gas- trointestinal Events) study,42 omeprazole was compared with placebo in 3627 patients starting dual antiplatelet therapy with aspirin and clopidogrel. 