Proton pump inhibitor (PPI) medications have been found to interfere with the metabolism of clopi- dogrel. When clopidogrel is started, PPIs are often prescribed prophylactically to prevent gastrointestinal (GI) complica- tions such as ulceration and related bleeding34 due to dual antiplatelet therapy, in particular aspirin and clopidogrel.17 Coupled with concern about the GI precautions, there has been increased emphasis on the prevention of premature discontinuation of dual antiplatelet therapy, particularly in patients who have received a DES for whom 12 months of antiplatelet therapy is recommended.15 There have been retrospective reports of adverse cardio- vascular outcomes (eg, readmission for ACS) when the antiplatelet regimen of clopidogrel and aspirin is accompa- nied by PPIs assessed as a group compared with use of this regimen without a PPI.17,35,36 In a retrospective cohort study Jneid et al 2012 UA/NSTEMI Focused Update 883 from the Veterans Affairs medical records and pharmacy database, concomitant clopidogrel and PPI therapy (with omeprazole, rabeprazole, lansoprazole, or pantoprazole) at any time during follow-up of 8205 patients discharged for ACS was associated with an increased risk of death or rehospitalization for ACS.17 Other post hoc study analyses25 and a retrospective data analysis from the National Heart, Lung, and Blood Institute Dynamic Registry, in which PPIs were assessed as a class in combination with a clopidogrel and an aspirin regimen, have not found an effect of PPI therapy on the clinical effect of clopidogrel in ACS patients, post-ACS patients, and a general post-PCI population, Some studies have suggested that adverse cardiovascular outcomes with the combination of clopidogrel and a PPI are explained by the individual PPI, in particular, the use of a PPI that inhibits CYP450 2C19, including omeprazole, lansopra- zole, or rabeprazole. 