Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown.
The authors conducted a population-based nested case–control study among patients aged 66 years or older who commenced clopidogrel between April 1, 2002 and December 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. The authors performed a secondary analysis considering events within one year. Event-free controls (at a ratio of 3:1) were matched to cases on age, percutaneous coronary intervention and a validated risk score. They categorized exposure to proton pump inhibitors before the index date as current (within 30 days), previous (31–90 days) or remote (91–180 days).
Among 13,636 patients prescribed clopidogrel following acute myocardial infarction, the investigators identified 734 cases readmitted with myocardial infarction and 2,057 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). The investigators 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).
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.