title: Platelet function variability and non-genetic causes.
abstract: Dual antiplatelet therapy (DAPT) has been established for the treatment of coronary artery disease, especially in and after acute coronary syndromes, and after coronary interventions. Data suggest that a significant percentage of individuals treated with clopidogrel do not receive the expected therapeutic benefit because of a decreased responsiveness of their platelets, which is caused by several extrinsic and intrinsic mechanisms. The clinical consequence of clopidogrel non-responsiveness is severe cardiovascular complications. Besides genetic variability in response to antiplatelet therapy, non-genetic causes such as drug interactions (proton-pump inhibitors, statins, calcium-channel blockers, coumarin derivates, antibiotics, antimycotics) and co-morbidities (diabetes mellitus, renal failure, obesity) are responsible for this phenomenon. Large clinical trials with standardised laboratory methods and hard clinical endpoints are needed to identify these interactions with clopidogrel and predictors for its non-responsiveness.
authors.affiliation: 3rd Department of Medicine, Cardiology and Emergency Medicine, Wilhelminenhospital, Montleartstrasse 37, Vienna, Austria.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Tentzeris
authors.forename: Jolanta
authors.initials: J
authors.lastname: Siller-Matula
authors.forename: Serdar
authors.initials: S
authors.lastname: Farhan
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jarai
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002986:Clinical Trials as Topic; D000077144:Clopidogrel; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000453:epidemiology*; D004347:Drug Interactions; D004351:Drug Resistance; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine