title: Consistent platelet inhibition during long-term maintenance-dose clopidogrel therapy among 359 compliant outpatients with documented vascular disease.
abstract: BACKGROUND
  Numerous reports have dichotomized responses after clopidogrel therapy using varying definitions and platelet tests in patients immediately after acute vascular events; however, no large study has assessed platelet characteristics in outpatients receiving long-term treatment for more than 30 days with the maintenance dose (75 mg/d) of clopidogrel. The aim of this study was to describe the responses of ex vivo measures of platelet aggregation and activation to long-term clopidogrel therapy in a large population of outpatients after coronary stenting or ischemic stroke.
  
  
  METHODS
  We conducted a secondary post hoc analysis of a data set represented by presumably compliant patients after coronary stenting (n = 237) or a documented ischemic stroke (n = 122) treated with clopidogrel-and-aspirin combination antiplatelet therapy.
  
  
  RESULTS
  The mean duration of treatment was 5.8 months (range 1-21 months). Every patient exhibited a significant inhibition of adenosine diphosphate-induced platelet aggregation (mean 52.9%, range 36%-70%) as compared with the preclopidogrel measures. Inhibition of aggregation strongly correlated with a diminished expression of PECAM-1 (platelet/endothelial cell adhesion molecule 1, r = 0.75), glycoprotein IIb/IIIa (r = 0.62), and PAR-1 (protease-activated receptor 1, r = 0.71). None of the patients developed hyporesponsiveness (reduction from the baseline <15%) or profound inhibition (residual platelet activity <10%).
  
  
  CONCLUSIONS
  In contrast to the wide variability of responses that exists in the acute setting, long-term therapy with clopidogrel leads to consistent and much less variable platelet inhibition. Lack of nonresponse and profound inhibition with clopidogrel allow for the maintenance of a delicate balance between proven efficacy and acceptable bleeding risks for long-term secondary prevention in outpatients after acute vascular events.
authors.affiliation: HeartDrug Research Laboratories, Johns Hopkins University, Towson, MD 21204, USA. heartdrug@aol.com
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
authors.forename: Alex I
authors.initials: AI
authors.lastname: Malinin
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.forename: Dan F
authors.initials: DF
authors.lastname: Hanley
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D039661:Integrin beta3 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D010979:Platelet Function Tests; D040201:Platelet Membrane Glycoprotein IIb / Q000097:blood; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014652:Vascular Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D039661:Integrin beta3; D010975:Platelet Aggregation Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040201:Platelet Membrane Glycoprotein IIb; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin