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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 antiplatelet effect of clopidogrel. This paper sought to characterise whether the use of clopidogrel and PPI concomitantly was associated with adverse outcomes after hospital discharge for myocardial infarction (MI).
The study was a population-based nested case–control study of patients aged ⩾66 years who were discharged from hospital after treatment for acute MI. Cases in the study were those who were readmitted with MI within 90 days, and were compared with age- and risk-matched event-free controls. Use of PPI was categorised as current (within 30 days), previous (31–90 days) or remote (91–180 days).
Of 13 636 patients prescribed clopidogrel after acute MI, 734 cases were readmitted. After multivariable adjustment, current use of PPI was associated with an increased risk of reinfarction (adjusted odds ratio = 1.27, 95% confidence interval 1.03 to 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.
A randomised trial is now required to prove if a clinically significant association exists, as is suggested by this study. If this proves to be the case, then the use of a PPI will have to be considered very carefully in patients taking combination therapy of aspirin and clopidogrel.
▸ Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009 Jan 28. [Epub ahead of print]. DOI: 10.1503/cmaj.082001.
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