Interaction between clopidogrel and PPI can lead to increased mortality

Emerging evidence indicates that proton-pump inhibitors (PPI) may inhibit cytochrome P450 2C19, an enzyme that plays a critical role in influencing the anti-platelet effect of clopidogrel.  This paper sought to characterize whether the use of clopidogrel and PPI concomitantly was associated with adverse outcomes following hospital discharge for myocardial infarction (MI).

The study was a population-based nested case-control study of patients aged 66 years and older who were discharged from hospital after treatment for acute myocardial infarction.  Cases in the study where those who were readmitted with a myocardial infarction within 90days, and were compared to age- and risk-matched event free controls.  Use of PPI was categorized as current (within 30 days), previous (31-90 days) or remote (91-180 days).

Of 13636 patients prescribed clopidogrel following acute myocardial infarction, 734 cases were readmitted.  After multivariable adjustment, current use of proton pump inhibitors was associated with an increased risk of reinfarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03-1.57); however no association was found with more distant use.  Importantly, no association was found between pantoprazole use and readmission for MI – pantoprazole does not inhibit cytochrome P450 2C19.

Almost all patients taking clopidogrel also take aspirin, and for these patients the use of a PPI must now be considered extremely carefully.  On a broader scale, the result of this study will come as a blow to many advocates of a cardiovascular ‘polypill’.

·       Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009; DOI: 10.1503/cmaj.082001

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