RT Journal Article
SR Electronic
T1 A population-based study of the drug interaction between proton pump inhibitors and clopidogrel
JF Canadian Medical Association Journal
JO CMAJ
FD Canadian Medical Association
SP 713
OP 718
DO 10.1503/cmaj.082001
VO 180
IS 7
A1 David N. Juurlink
A1 Tara Gomes
A1 Dennis T. Ko
A1 Paul E. Szmitko
A1 Peter C. Austin
A1 Jack V. Tu
A1 David A. Henry
A1 Alex Kopp
A1 Muhammad M. Mamdani
YR 2009
UL http://www.cmaj.ca/content/180/7/713.abstract
AB 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.