Some PPIs reduce the effects of clopidogrel

Korean researchers have examined the effects of co-administration of proton pump inhibitors (PPIs) or statins with clopidogrel, using pharmacoepidemiological data. The basis for the study was that PPIs or CYP3A4‐metabolized statins might increase thee risk for thrombotic events by reducing the effects of clopidogrel by diminishing thee formation of the active metabolite of clopidogrel by altering the activity of CYP enzyme. Korean nationwide claims  was used to examine the cases of 59,233 patients who initiated clopidogrel and statins after coronary stenting, comparing thrombotic risks by PPI or CYP3A4‐metabolized statin use or both. The concurrent use of PPIs with clopidogrel was associated with increased thrombotic risks (hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12–1.45), but this was not observed with co-administration of CYP3A4‐metabolized statins (HR 1.03, 95% CI 0.98–1.07). The use of PPIs with high activity in inhibiting CYP2C19 were more relevant than those with low potential (HR 1.28, 95% CI 1.02–1.61). More information about thee study can be viewed here, but the take home message is that caution is needed if clopidogrel is concurrently used for people treated with PPIs, in particular esomeprazole, omeprazole and lansoprazole. A cautionary note in interpretation – as the study involved a Korean population, the profile of CYP2C19 in this group may not necessary reflect that seen for people of other ethnicities.