title: Clopidogrel and proton pump inhibitors: influence of pharmacological interactions on clinical outcomes and mechanistic explanations.
abstract: Dual antiplatelet therapy with aspirin and clopidogrel is associated with a significant reduction in vascular ischemic events; however, gastrointestinal bleeding events are a major concern in high-risk and older patients. Clinical practice guidelines recommend combination therapy with proton pump inhibitors (PPI) and dual antiplatelet therapy to attenuate gastrointestinal bleeding risk. In addition, high on-treatment platelet reactivity has been associated with recurrent ischemic events. Whether or not the pharmacological interaction between clopidogrel and PPI, which results in diminished antiplatelet effect, adversely influences clinical efficacy is highly controversial and the subject of debate. Based on largely anecdotal post-hoc analyses, the U.S. Federal Drug Administration's and European Medicines Agency's recommendations discourage PPI use (particularly omeprazole) in patients treated with clopidogrel. However, many American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions experts do not support change in clinical practice guidelines recommendations without adequately powered, prospective, randomized clinical trial data.
authors.affiliation: Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland 21215, USA.
authors.forename: Udaya S
authors.initials: US
authors.lastname: Tantry
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Kereiakes
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
mesh_terms: D000818:Animals; D001711:Biotransformation / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D000077144:Clopidogrel; D004347:Drug Interactions; D019317:Evidence-Based Medicine; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D017410:Practice Guidelines as Topic; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine