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Commentary on Douglas IJ Evans SJ Hingorani AD . Clopidogrel and interaction with proton pump inhibitors: comparison between cohort and within person study designs . BMJ 2012 ; 345 : e4388
Context
Clopidogrel inhibits the P2Y12 platelet receptor and is used in patients with acute coronary syndromes or ischaemic stroke to prevent recurrent vascular events. Proton pump inhibitors (PPIs), however, have been shown to reduce the pharmacodynamic effect of clopidogrel upon platelet inhibition, and have been linked in retrospective studies to a higher rate of ischaemic outcomes in patients taking clopidogrel.
Methods
A total of 24 471 patients in the General Practice Research Database in the UK (beginning in 2003) concurrently prescribed aspirin and clopidogrel were included. There were 12 439 (50%) patients receiving a PPI at some point during the study. The exposure of interest was prescription of a PPI, divided into strong CYP 2C19 inhibitors (omeprazole, esomeprazole and lansoprazole) and not strong inhibitors (other PPIs). Exposure to other strong 2C19 inhibitors (fluoxetine and paroxetine) was also assessed. The primary outcome was a composite of myocardial infarction (MI) or all-cause mortality; secondary outcomes included MI, all-cause mortality, vascular mortality and non-vascular mortality. Patients were followed from 2003 until 2009, although some were censored if...