Impact of clopidogrel resistance on thrombotic events after percutaneous coronary intervention with drug-eluting stent.
OBJECTIVE
This study examines whether patient resistance to clopidogrel is associated with long-term thrombotic events after elective coronary drug-eluting stent (DES) implantation.


METHODS
We prospectively enrolled 386 patients with stable angina who received elective percutaneous coronary intervention (PCI) with DES. Before the procedure, platelet reactivity was measured by light transmittance aggregometry (LTA) at baseline and approximately 24 h after the 300 mg loading dose of clopidogrel. Clopidogrel resistance was conservatively defined as < or = 10% absolute difference between baseline and post-treatment platelet aggregation. All patients received chronic dual antiplatelet treatment (aspirin 300 mg and clopidogrel 75 mg daily) for 12 months. Patients were followed for 1 year after coronary stenting for the occurrence of composite thrombotic events, including cardiovascular death, non-fatal myocardial infarction (MI), stent thrombosis or cerebrovascular ischemic accident (CVA).


RESULTS
Clopidogrel resistance was present in 65 patients (16.8%). During follow-up, composite thrombotic events occurred in 16.9% of clopidogrel resistant patients, yet in only 6.2% of non-resistant patients (p = 0.010). The incidence of definite or probable stent thrombosis was 9.2% in clopidogrel resistant patients and 2.5% in non-resistant patients (p = 0.018). After adjustment for other factors that affect cardiovascular outcome, clopidogrel resistance, diabetes, and left ventricular (LV) dysfunction were independently associated with 1-year composite thrombotic events. The hazard ratio (HR) for clopidogrel resistance was 2.44 (95% CI = 1.09 to 5.45; p = 0.031).


CONCLUSIONS
This study demonstrates the natural history of clopidogrel resistance among patients with stable cardiovascular disease, and shows that this resistance is an independent predictor of thrombotic events in patients undergoing PCI with DES.
Wang
Zhi Jian
ZJ
Department of Cardiology, Anzhen Hospital, Capital Medical University, Anzhenli district, Beijing, China.
Zhou
Yu Jie
YJ
Liu
Yu Yang
YY
Yu
Miao
M
Shi
Dong Mei
DM
Zhao
Ying Xin
YX
Guo
Yong He
YH
Cheng
Wan Jun
WJ
Jia
De An
de A
Cao
Zheng
Z
Nie
Bin
B
Ge
Hai Long
HL
Yang
Shi Wei
SW
Yan
Zhen Xian
ZX
D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000379:methods*; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000209:etiology; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic / Q000592:standards; D020123:Sirolimus / Q000627:therapeutic use; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D020123:Sirolimus