Dynamic changes and associated factors of clopidogrel resistance in patients after cerebral infarction

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Abstract
Stroke victims often exhibit clopidogrel resistance (CR). This prospective study was undertaken to observe changes that influence CR in the secondary prevention of cerebral infarction (CI). The study included 56 cases at high risk of stroke (HRS), 147 cases of CI and 68 control subjects. The CI and HRS groups were divided into CR and NCR (none clopidogrel resistance) subgroups using standard criteria. The NCR group was subdivided into DCR (dynamic CR) and CNCR (continuous NCR) groups. Platelet aggregation rate (PAR) was assessed at baseline and after 2 weeks treatment with clopidogrel 75 mg/day in the CI and HRS groups. In the NCR group, PAR was evaluated after 3 and 6 months of clopidogrel (75 mg/day) treatment. Baseline PAR was higher in the CI group than in the HRS or control groups (P < 0.01). The incidence of CR was 28.6 % in the CI and 13.6 % in the HRS group (P = 0.018). Diabetes mellitus, (OR 16.627; 95 % CI 4.691–58.934) and history of TIA (OR 13.711; 95 % CI 1.667–112.784) (both P < 0.05) were both associated with CR. Other independent risk factors included high total cholesterol, calcium antagonist or ACEI/ARB use. A total of 36 CR and 85 NCR cases completed 6 months follow-up. High total cholesterol was an independent risk factor for DCR (OR 0.415; 95 % CI 0.213–0.808; P = 0.01) which developed in 15 subjects at 6 months. PAR decreased by >10 % after 2 weeks in 71.4 % of patients with CR who subsequently changed drugs or received combination therapy. Dynamic CR may occur after CI. Many factors including DM\TIA\HCT\P2Y12 εC coexistence CYP2Y19 εA\combination drug, associate CR or DCR. Our results highlight the need for PAR monitoring.

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