Comparative Risk of Ischemic Stroke Among Users of Clopidogrel Together With Individual Proton Pump Inhibitors

BACKGROUND AND PURPOSE: There is controversy and little information about whether individual proton pump inhibitors (PPIs) differentially alter the effectiveness of clopidogrel in reducing ischemic stroke risk. We, therefore, aimed to elucidate the risk of ischemic stroke among concomitant users of clopidogrel and individual PPIs. METHODS: We conducted a propensity score-adjusted cohort study of adult new users of clopidogrel, using 1999 to 2009 Medicaid claims from 5 large states. Exposures were defined by prescriptions for esomeprazole, lansoprazole, omeprazole, rabeprazole, and pantoprazole-with pantoprazole serving as the referent. The end point was hospitalization for acute ischemic stroke, defined by International Classification of Diseases Ninth Revision Clinical Modification codes in the principal position on inpatient claims, within 180 days of concomitant therapy initiation. RESULTS: Among 325 559 concomitant users of clopidogrel and a PPI, we identified 1667 ischemic strokes for an annual incidence of 2.4% (95% confidence interval, 2.3-2.5). Adjusted hazard ratios for ischemic stroke versus pantoprazole were 0.98 (0.82-1.17) for esomeprazole; 1.06 (0.92-1.21) for lansoprazole; 0.98 (0.85-1.15) for omeprazole; and 0.85 (0.63-1.13) for rabeprazole. CONCLUSIONS: PPIs of interest did not increase the rate of ischemic stroke among clopidogrel users when compared with pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel.