A population-based study of the drug interaction between proton pump inhibitors and clopidogrel
By D. Juurlink, T. Gomes, Dennis T. Ko, P. Szmitko, Peter C. Austin, J. Tu, D. Henry, A. Kopp, M. Mamdani. Canadian Medical Association Journal, 2009
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Background: Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown. Methods: We conducted a population-based nested case–control study among patients aged 66 years or older who commenced clopidogrel between Apr. 1, 2002, and Dec. 31, 2007, following hospital discharge after treatment of acute myocardial infarction. The cases in our study were those readmitted with acute myocardial infarction within 90 days after discharge. We performed a secondary analysis considering events within 1 year. Event-free controls (at a ratio of 3:1) were matched to cases on age, percutaneous coronary intervention and a validated risk score. We categorized exposure to proton pump inhibitors before the index date as current (within 30 days), previous (31–90 days) or remote (91–180 days). Results: Among 13 636 patients prescribed clopidogrel following acute myocardial infarction, we identified 734 cases readmitted with myocardial infarction and 2057 controls. After extensive 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). We found no association with more distant exposure to proton pump inhibitors or in multiple sensitivity analyses. In a stratified analysis, pantoprazole, which does not inhibit cytochrome P450 2C19, had no association with readmission for myocardial infarction (adjusted OR 1.02, 95% CI 0.70–1.47). Interpretation: Among patients receiving clopidogrel following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopidogrel and an increased risk of reinfarction.
Subfields: Cardiology and Cardiovascular Medicine, Pharmacology
View Paper: https://www.semanticscholar.org/paper/5cde262ec9ccb99b02bf85c8ae5f4852dc02fac0
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In Cardiology and Cardiovascular Medicine
Citations in the corpus
- 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST‐Elevation Myocardial Infarction (Updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (Updating the 2005 Guideline and 2007 Focused Update) (2009, background): “One study reported that the PPI pantoprazole was not associated with recurrent MI among patients receiving clopidogrel, possibly because of its lack of inhibition of CYP450 2C19.(33) Other studies have examined the thienopyridine agent prescribed with the PPI.”