Consistent platelet inhibition during long-term maintenance-dose clopidogrel therapy among 359 compliant outpatients with documented vascular disease.
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.
Serebruany
Victor L
VL
HeartDrug Research Laboratories, Johns Hopkins University, Towson, MD 21204, USA. heartdrug@aol.com
Malinin
Alex I
AI
Atar
Dan
D
Hanley
Dan F
DF
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
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