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PPIs and clopidogrel
Increasing evidence suggests that proton pump inhibitors (PPIs) may attenuate the effect of clopidogrel on platelet aggregation. PPIs are often used prophylactically in patients with acute coronary syndrome (ACS), as patients on clopidogrel and aspirin may be at higher risk for GI bleeding. A new study from VA researchers was set up to determine if there are clinical implications from the interaction between PPIs and clopidogrel.
In a retrospective cohort study of 8205 patients with ACS taking clopidogrel, 63.9% were also prescribed a PPI at discharge, during follow-up, or both. Death or rehospitalization for ACS occurred in 20.8% of patients taking clopidogrel without a PPI and 29.8% patients taking clopidogrel with a PPI. Use of clopidogrel plus a PPI was associated with an increased risk of death or rehospitalization for ACS compared with use of clopidogrel without a PPI (adjusted odds ratio, 1.25; 95% confidence interval, 1.11-1.41). Patients taking a combination of the two drugs were at higher risk for hospitalizations for ACS and revascularization procedures, but not for all-cause mortality. Patients taking a PPI without clopidogrel were not at higher risk for rehospitalization. The authors conclude that concomitant use of clopidogrel and a PPI after hospital discharge for ACS is associated with an increase risk of adverse outcomes, suggesting that PPIs may attenuate the benefits of clopidogrel, and that PPIs should only be used with clopidogrel if there is a clear indication, and not for routine prophylaxis (JAMA 2009;301:937-944).