Proton Pump Inhibitors Effect on Clopidogrel Effectiveness: The Clopidogrel Medco Outcomes Study

Ronald E Aubert
16 nov 2008--Background: The anti-platelet properties of clopidogrel are thought to be activated by cytochrome P450 2C19. This isoenzyme is potently inhibited by the most commonly prescribed proton pump inhibitors (PPIs) and therefore may interfere with clopidogrel activation and its anti-platelet effects.

Methods: We investigated the potential impact of PPIs on the effectiveness of clopidogrel to prevent coronary artery stent re-stenosis through a retrospective cohort study using the National Medco Integrated Database file, which covers approximately 19 million lives. We selected patients who underwent stent placement at sometime during a one-year period in 2005–2006, who started taking clopidogrel at the time of stent placement, and who were at least 80% compliant during the ensuing year (n=14,383). We followed these patients for the one-year incidence of major adverse CV events: hospitalization for stroke, MI, angina or CABG. We compared those who took clopidogrel alone (n=9862) vs. those who took clopidogrel with PPIs (n=4521), adjusting for baseline differences in age, gender and comorbidity.

Results: Stent patients with no preceding CV events taking PPIs with clopidogrel showed a 32.5% incidence of a major CV event within one year vs. 21.2% of patients not taking PPIs (adjusted OR 1.79, CI 1.62–1.97). A more pronounced effect was seen among patients with a preceding CV event; 39.8% vs 26.2% (adjusted OR of 1.86, CI 1.63–2.12).

Conclusions: Our findings suggest that the drug interaction between PPIs and clopidogrel may result in serious adverse outcomes within one year of therapy initiation, and further support investigations into the effects of cytochrome P450 2C19 genetic polymorphisms.