Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis.
OBJECTIVE
We sought to determine whether nonresponsiveness to clopidogrel as revealed by high in vitro post-treatment platelet reactivity is predictive of drug-eluting stent (DES) thrombosis.


BACKGROUND
No data exist about the impact of nonresponsiveness to clopidogrel on the risk of DES thrombosis.


METHODS
We conducted a prospective observational cohort study from July 2005 to August 2006 in an academic hospital. A total of 804 patients who had successful sirolimus- or paclitaxel-eluting stent implantation were assessed for post-treatment platelet reactivity after a loading dose of 600 mg of clopidogrel. Patients with platelet aggregation by 10 mumol adenosine 5'-diphosphate > or =70% were defined as nonresponders. All patients received chronic dual antiplatelet treatment (aspirin 325 mg and clopidogrel 75 mg daily) for 6 months. The primary end point was the incidence of definite/probable early, subacute, and late stent thrombosis at 6-month follow-up.


RESULTS
The incidence of 6-month definite/probable stent thrombosis was 3.1%. All stent thromboses were subacute or late. Of 804 patients, 105 (13%) were not responsive to clopidogrel. The incidence of stent thrombosis was 8.6% in nonresponders and 2.3% in responders (p < 0.001). By multivariate analysis, the predictors of stent thrombosis were as follows: nonresponsiveness to clopidogrel (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.32 to 7.16; p = 0.009), left ventricular ejection fraction (HR 0.95, 95% CI 0.92 to 0.98; p = 0.001), total stent length (HR 1.01, 95% CI 1.00 to 1.02; p = 0.010), and ST-segment elevation acute myocardial infarction (HR 2.41, 95% CI 1.04 to 5.63; p = 0.041).


CONCLUSIONS
Nonresponsiveness to clopidogrel is a strong independent predictor of stent thrombosis in patients receiving sirolimus- or paclitaxel-eluting stents.
Buonamici
Piergiovanni
P
Department of Cardiology, Careggi Hospital, Florence, Italy.
Marcucci
Rossella
R
Migliorini
Angela
A
Gensini
Gian Franco
GF
Santini
Alberto
A
Paniccia
Rita
R
Moschi
Guia
G
Gori
Anna Maria
AM
Abbate
Rosanna
R
Antoniucci
David
D
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D015897:Comorbidity; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000628:therapy; D017239:Paclitaxel / Q000008:administration & dosage; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010979:Platelet Function Tests; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage; D015607:Stents / Q000009:adverse effects*; D013927:Thrombosis / Q000503:physiopathology / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D007166:Immunosuppressive Agents; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D017239:Paclitaxel; D020123:Sirolimus