title: Comparative risk of ischemic stroke among users of clopidogrel together with individual proton pump inhibitors.
abstract: OBJECTIVE
  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.
authors: From the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.). celeonar@mail.med.upenn.edu.
authors: Charles E
authors: CE
authors: Leonard
authors: From the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
authors: Warren B
authors: WB
authors: Bilker
authors: From the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
authors: Colleen M
authors: CM
authors: Brensinger
authors: From the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
authors: David A
authors: DA
authors: Flockhart
authors: From the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
authors: Cristin P
authors: CP
authors: Freeman
authors: From the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
authors: Scott E
authors: SE
authors: Kasner
authors: From the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
authors: Stephen E
authors: SE
authors: Kimmel
authors: From the Center for Clinical Epidemiology and Biostatistics (C.E.L., W.B.B., C.M.B., C.P.F., S.E. Kimmel, S.H.), Center for Pharmacoepidemiology Research and Training (C.E.L., W.B.B., D.A.F., C.P.F., S.E. Kimmel, S.H.), Department of Psychiatry (W.B.B.), Department of Neurology (S.E. Kasner), Division of Cardiovascular Medicine, Department of Medicine (S.E. Kimmel), and Department of Systems Pharmacology and Translational Therapeutics (S.H.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; and Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis (D.A.F.).
authors: Sean
authors: S
authors: Hennessy
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000139:chemically induced* / Q000517:prevention & control; D000077144:Clopidogrel; D003627:Data Interpretation, Statistical; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D064098:Esomeprazole / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D064747:Lansoprazole / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects; D000077402:Pantoprazole; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D064750:Rabeprazole / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012306:Risk; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D064750:Rabeprazole; D000077144:Clopidogrel; D000077402:Pantoprazole; D009853:Omeprazole; D064098:Esomeprazole; D013988:Ticlopidine
keywords: Medicaid; cohort studies; drug interactions; pharmacoepidemiology; platelet aggregation inhibitors; proton pump inhibitors; stroke
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