Interaction between proton pump inhibitors and clopidogrel
Introduction: Proton pump inhibitors (PPI) may impair the biotransformation of clopidogrel leading to increased major adverse cardiac events (MACE). Available studies have focused solely on patients receiving clopidogrel following a cardiac event. Given the widespread use of this combination, (about 64% in a recent study), this represents a major interaction that deserves further study. The objective of this thesis was to determine if the potential interaction between PPIs and clopidogrel leads to an increase in MACE in high-risk atherosclerotic patients receiving clopidogrel and PPIs as compared to clopidogrel alone. Methods: We conducted a retrospective chart review of patients in the University Hospital System who received clopidogrel between January 1, 2007 and April 30, 2009. Patients were included if they were hospitalized for acute coronary syndromes, stroke/TIA, revascularization (coronary, cerebral or peripheral arteries), or aspirin allergy. The primary outcome was the composite of myocardial infarction (MI), stroke/transient ischemic attack (TIA), coronary artery revascularization, or death (all cause) during the first year following discharge. Secondary outcomes included the composite of MI, stroke /TIA, revascularization (coronary, cerebral or peripheral arteries), or death. Bivariate analyses were conducted using Student’s t test, Mann Whitney U and Chi-square tests where appropriate. Multivariate analysis was conducted to adjust for baseline differences. Results: Overall, 1700 charts were reviewed and 572 patients met study criteria. The median follow-up was 332 days. The most common indication for clopidogrel use was coronary artery revascularization (66%). There were 201 patients in the clopidogrel with PPI group and 371 patients in the clopidogrel without PPI group. Baseline characteristics were evenly matched between both groups except for smoking, liver disease, and prior receipt of a PPI. The primary endpoint occurred in 21 patients in the clopidogrel with PPI group and 38 patients in the clopidogrel without PPI group (10% vs. 10%, p = 0.9, OR 1.02, 95% CI 0.58 – 1.80). The primary endpoint was unchanged after multivariate adjustments for baseline differences (adjusted OR 0.98, 95% CI 0.54 – 1.75). Likewise, there was no difference in the secondary endpoint (14% vs. 15%, p = 0.8, OR 1.02; 95% CI 0.58 – 1.80). The secondary endpoint was also unchanged after multivariate adjustments for baseline differences (adjusted OR 1.04, 95% CI (0.61 – 1.75) Conclusion: Patients receiving clopidogrel with a PPI demonstrated similar rates of MACE when compared to patients receiving clopidogrel without a PPI.