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A population-based study of the drug interaction between proton pump inhibitors and clopidogrel.
- Source :
-
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne [CMAJ] 2009 Mar 31; Vol. 180 (7), pp. 713-8. Date of Electronic Publication: 2009 Jan 28. - Publication Year :
- 2009
-
Abstract
- Background: Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown.<br />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).<br />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).<br />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.
- Subjects :
- Age Distribution
Aged
Aged, 80 and over
Angioplasty, Balloon, Coronary methods
Case-Control Studies
Clopidogrel
Cohort Studies
Confidence Intervals
Continuity of Patient Care
Drug Therapy, Combination
Female
Follow-Up Studies
Humans
Incidence
Male
Multivariate Analysis
Myocardial Infarction diagnosis
Myocardial Infarction epidemiology
Myocardial Infarction therapy
Odds Ratio
Patient Discharge
Proton Pump Inhibitors administration & dosage
Recurrence
Risk Assessment
Sex Distribution
Survival Rate
Ticlopidine administration & dosage
Ticlopidine adverse effects
Drug Interactions
Myocardial Infarction drug therapy
Patient Readmission statistics & numerical data
Proton Pump Inhibitors adverse effects
Ticlopidine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1488-2329
- Volume :
- 180
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne
- Publication Type :
- Academic Journal
- Accession number :
- 19176635
- Full Text :
- https://doi.org/10.1503/cmaj.082001