A population-based study of the drug interaction between proton pump inhibitors and clopidogrel

David N. Juurlink, Tara Gomes, Dennis T. Ko, Paul E. Szmitko, Peter C. Austin, Jack V. Tu, David A. Henry, Alex Kopp, Muhammad Mamdani

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Abstract

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 (91180 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.

Original languageEnglish
Pages (from-to)713-718
Number of pages6
JournalCMAJ
Volume180
Issue number7
DOIs
Publication statusPublished - 31 Mar 2009
Externally publishedYes

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clopidogrel
Proton Pump Inhibitors
Drug Interactions
Myocardial Infarction
Population
Odds Ratio
Confidence Intervals
Percutaneous Coronary Intervention
Cytochrome P-450 Enzyme System
Case-Control Studies

Cite this

Juurlink, D. N., Gomes, T., Ko, D. T., Szmitko, P. E., Austin, P. C., Tu, J. V., ... Mamdani, M. (2009). A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ, 180(7), 713-718. https://doi.org/10.1503/cmaj.082001
Juurlink, David N. ; Gomes, Tara ; Ko, Dennis T. ; Szmitko, Paul E. ; Austin, Peter C. ; Tu, Jack V. ; Henry, David A. ; Kopp, Alex ; Mamdani, Muhammad. / A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. In: CMAJ. 2009 ; Vol. 180, No. 7. pp. 713-718.
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abstract = "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 (91180 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.",
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Juurlink, DN, Gomes, T, Ko, DT, Szmitko, PE, Austin, PC, Tu, JV, Henry, DA, Kopp, A & Mamdani, M 2009, 'A population-based study of the drug interaction between proton pump inhibitors and clopidogrel' CMAJ, vol. 180, no. 7, pp. 713-718. https://doi.org/10.1503/cmaj.082001

A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. / Juurlink, David N.; Gomes, Tara; Ko, Dennis T.; Szmitko, Paul E.; Austin, Peter C.; Tu, Jack V.; Henry, David A.; Kopp, Alex; Mamdani, Muhammad.

In: CMAJ, Vol. 180, No. 7, 31.03.2009, p. 713-718.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Gomes, Tara

AU - Ko, Dennis T.

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AU - Austin, Peter C.

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AU - Henry, David A.

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AU - Mamdani, Muhammad

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N2 - 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 (91180 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.

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Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-718. https://doi.org/10.1503/cmaj.082001