title: Genetic and non-genetic factors affecting the response to clopidogrel therapy.
abstract: BACKGROUND
  Clopidogrel (CLP) is a second-generation thienopyridine that prevents platelet aggregation by inhibiting the adenosine diphosphate receptor located on the platelet surface. The use of CLP in combination with aspirin has become standard treatment in patients with acute coronary syndromes and stent implantation. Data suggests that a significant percentage of individuals treated with CLP do not receive the expected therapeutic benefit because of a decreased platelet inhibition. The clinical consequences of an inadequate platelet response are cardiovascular complications, which can lead to acute myocardial infarction, stroke and death. The mechanism underlying CLP resistance is multifactorial and includes genetic polymorphisms and non-genetic causes (such as drug-drug interactions, co-morbidities, age).
  
  
  METHODS
  This article reviews the so-far accumulated evidence on the role of genetic polymorphisms and non-genetic factors, as determinants of the antiplatelet response to CLP. Pharmacodynamic and clinical aspects of the CLP nonresponsiveness are also presented. Relevant papers were identified by an extensive PubMed search using appropriate keywords.
  
  
  CONCLUSIONS
  Impaired platelet inhibition in CLP poor responders is a real problem, as it leads to serious clinical consequences. Therefore, prediction models that include pharmacogenetic knowledge and non-genetic risk factors of low response to the drug are needed in the individualization of antithrombotic therapy. Alternative antiplatelet strategies that should be considered to overcome this problem include dose modification, adjunctive antiplatelet drug usage, and use of newer agents.
authors.affiliation: Poznan University of Medical Sciences, Department of Physical Pharmacy and Pharmacokinetics, 6 Święcickiego Street, 60-781 Poznań, Poland. mkaraz@ump.edu.pl
authors.forename: Marta
authors.initials: M
authors.lastname: Karaźniewicz-Łada
authors.forename: Dorota
authors.initials: D
authors.lastname: Danielak
authors.forename: Franciszek
authors.initials: F
authors.lastname: Główka
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics*; D000077144:Clopidogrel; D004347:Drug Interactions; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine