title: Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump Inhibitors Using the FDA Adverse Event Reporting System Database.
abstract: Clopidogrel is an antiplatelet agent widely used in combination with aspirin to limit the occurrence of cardiovascular (embolic/thrombotic) events. Consensus guidelines recommend proton pump inhibitors (PPIs) as a gastrointestinal (GI) prophylactic measure for all patients receiving dual antiplatelet therapy with clopidogrel and aspirin. The objective of this study was to analyze the effect of the simultaneous use of clopidogrel, aspirin, and PPIs on hemorrhagic and embolic/thrombotic events using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reports of hemorrhagic and embolic/thrombotic events between 2004 and 2013 were analyzed with a reporting odds ratio (ROR) algorithm and logistic regression methods. The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify such events. Regarding hemorrhagic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 4.40 (95% confidence interval [CI], 4.02-4.81) and 3.40 (95% CI, 2.84-4.06), respectively. For embolic/thrombotic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 2.37 (95% CI, 2.16-2.59) and 2.38 (95% CI, 2.00-2.84), respectively. Among patients included in the FAERS database, the concurrent use of aspirin and clopidogrel with PPIs reduced the adjusted ROR of GI hemorrhagic events. PPIs had little influence on the adjusted ROR of embolic/thrombotic events. These results support the use of PPIs as a preventive measure against GI hemorrhagic events for patients receiving clopidogrel and aspirin.
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University; 1–25–4 Daigaku-Nishi, Gifu 501–1196 2. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University 1–25–4  Daigaku-Nishi, Gifu 501–1196, Japan.
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Honami
authors.initials: H
authors.lastname: Suzuki
authors.forename: Ryogo
authors.initials: R
authors.lastname: Umetsu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Uranishi
authors.forename: Junko
authors.initials: J
authors.lastname: Abe
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nishibata
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Sekiya
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Miyamura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Teruo
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kinosada
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use; D000077144:Clopidogrel; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004617:Embolism / Q000517:prevention & control*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D013927:Thrombosis / Q000517:prevention & control*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin