Combination of Proton Pump Inhibitors and Clopidogrel Associated with Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome or Myocardial Infarction
Two recent retrospective studies have examined cardiovascular outcomes associated with combining clopidogrel with proton pump inhibitors (PPIs). A case-control study with 13,636 elderly patients taking clopidogrel after hospitalization for acute myocardial infarction analyzed PPI use in patients readmitted for acute MI in < 90 days compared to event-free controls. Because pantoprazole is a much weaker inhibitor of cytochrome P450 2C19 than other PPIs, exposure to this agent was studied separately. Use of PPIs (other than pantoprazole) at < 30 days after discharge was significantly higher among the cases than controls (20.2% vs. 14.5%), but there was no difference in the rate of pantoprazole usage (6.1% vs. 6.3%) (level 2 [mid-level] evidence). There were no differences in mortality at 90 days or at 1 year. No relation was found between rehospitalization and use of H2 blockers (CMAJ 2009 Mar 31;180(7):713).
In a cohort study of 8,205 patients with acute coronary syndrome (ACS) taking clopidogrel at hospital discharge, concomitant use of PPIs was associated with higher rehospitalization rate for ACS (14.6% vs. 6.9%, p < 0.05, NNH 12) and more revascularization procedures (15.5% vs. 11.9%, p < 0.05, NNH 27) compared to non-use (level 2 [mid-level] evidence). These differences remained significant after adjustment for baseline differences in age and comorbidities. There was also a non-significant increase in all-cause mortality in the PPI group (19.9% vs. 16.6%). Use of PPIs was not associated with either death or rehospitalization for acute coronary syndrome in an additional cohort of 6,450 patients who were not taking clopidogrel after hospital discharge (JAMA 2009 Mar 4;301(9):937).
For more information, see the Antiplatelet agents for coronary artery disease, Antiplatelet agents for acute coronary syndrome, and Clopidogrel topics in DynaMed.
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