title: Inter-individual variability in response to clopidogrel in patients with coronary artery disease.
abstract: BACKGROUND
  Clopidogrel, especially when combined with aspirin, reduces the rate of ischaemic events in patients with coronary artery disease (CAD). There are scare data in literature on the inter-individual variability in response to clopidogrel.
  
  
  OBJECTIVE
  To assess the incidence of clopidogrel resistance using rapid whole blood platelet function assessment, and to examine the possibility of early identification of non-responders.
  
  
  METHODS
  In 31 consecutive patients with stable angina treated with aspirin, the degree of platelet aggregation inhibition (DPAI) in the whole blood was assessed at baseline and 3, 6, 12 as well as 24 hours after administration of loading dose of clopidogrel (300 mg). Response to clopidogrel was measured by calculating the absolute difference between the baseline DPAI and DPAI obtained at the investigated time-points (DPAI).
  
  
  RESULTS
  After 24 hours from clopidogrel administration, seven (22.6%) patients were identified as non-responders (DPAI < or =10%). Demographic and clinical variables as well as baseline DPAI were similar in responders and non-responders (DPAI: 5.8+/-3.7% vs 7.1+/-5.3%, p=NS). Out of the patients who were found to be resistant to clopidogrel at the six-hour time-point, 87.5% remained resistant to this agent 24 hours after drug administration. DPAI calculated at the 24-hour time-point highly correlated with the six-hour DPAI (r=0.74). No differences in the rate of ischaemic or bleeding complications between responders and non-responders were noted.
  
  
  CONCLUSIONS
  The assessment of the degree of platelet aggregation inhibition allows early (six hours from the initiation of treatment) identification of patients who are resistant to clopidogrel. The method of the rapid whole blood platelet function assessment is feasible in every-day clinical practice.
authors.affiliation: 2nd Department of Cardiology, Institute of Cardiology, Jagiellonian University College of Medicine, Cracow, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Dziewierz
authors.forename: Dariusz
authors.initials: D
authors.lastname: Dudek
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Heba
authors.forename: Tomasz
authors.initials: T
authors.lastname: Rakowski
authors.forename: Waldemar
authors.initials: W
authors.lastname: Mielecki
authors.forename: Jacek S
authors.initials: JS
authors.lastname: Dubiel
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine