The difference between clopidogrel responsiveness and posttreatment platelet reactivity.
BACKGROUND
Aggregation is the most common measure of platelet reactivity. The relative inhibition of platelet aggregation between pretreatment and posttreatment is the most common estimate of clopidogrel responsiveness. However, patients responsive to clopidogrel may remain with highly reactive platelets and thus have increased thrombotic risk.


METHODS
Platelet reactivity was determined by ADP-induced aggregation (%) in 62 patients undergoing elective coronary stenting at pretreatment and 5 days postprocedure. All patients were on aspirin (325 mg) and received 300 mg of clopidogrel immediately poststenting and 75 mg qd. Pretreatment reactivity was divided into tertiles. Based on clopidogrel drug responsiveness, nonresponders were defined as <10% relative inhibition of pretreatment aggregation, semiresponders as 10-30%, and responders as >30%. We determined the relation between clopidogrel responsiveness and platelet reactivity.


RESULTS
Pretreatment reactivity tertiles by 5 microM ADP were: low (47+/-9%), moderate (64+/-4%), and high (78+/-6%). Eight patients were nonresponders, 18 were semiresponders, and 36 were responders. Clopidogrel responsiveness directly correlated with pretreatment reactivity, 86% of responders had moderate or high pretreatment reactivity, whereas 75% of nonresponders had low pretreatment reactivity. Despite being more responsive, 16% of patients with high pretreatment reactivity and 17% with moderate pretreatment reactivity remained with moderate posttreatment reactivity.


CONCLUSIONS
Measuring clopidogrel responsiveness may overestimate the risk of stent thrombosis in nonresponders with low pretreatment reactivity and underestimate risk in those responders who remain with high posttreatment platelet reactivity. Posttreatment platelet reactivity is a better measure of thrombotic risk than responsiveness to clopidogrel.
Samara
Waiel M
WM
Sinai Center for Thrombosis Research, Hoffberger Building, Suite 56, 2401 West Belvedere Avenue, Baltimore, MD 21215, USA.
Bliden
Kevin P
KP
Tantry
Udaya S
US
Gurbel
Paul A
PA
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D011379:Prognosis; D012306:Risk; D015607:Stents / Q000009:adverse effects; D013927:Thrombosis / Q000209:etiology; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology
D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine