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

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.

The first six-month clinical outcomes and risk factors associated with high on-treatment platelet reactivity of clopidogrel in patients undergoing coronary interventions

“…In our study, we observed similar association in patients with coronary artery disease. High total cholesterol levels were also associated with HTPR in patients with cerebral infarct undergoing clopidogrel treatment ( 40 ). Moreover, we observed the same association in patients with coronary artery disease.…”

Stent alone treatment for dissections and dissecting aneurysms involving the basilar artery

“…Ischemic complications after treatment occurred in two patients. Previous reports indicated that levels of P2Y12, a platelet membrane protein receptor which plays a key role in platelet activation, vary in individuals and influence the effect of antiplatelet therapy 26 27. To reduce ischemic complications for these patients receiving reconstructive endovascular treatment, P2Y12 platelet function tests, to evaluate if there is P2Y12 resistance to antiplatelet therapy, and coagulogram tests, such as thrombelastography to monitor blood coagulation, may be helpful 27.…”

Platelet Function Testing in Patients with Acute Ischemic Stroke: An Observational Study

“…The finding of a lower responsiveness to Clopidogrel therapy in our stroke population is consistent with a wide variety of previous studies. 19,27,44 The phenomenon named "Clopidogrel resistance," highly variable in different populations (ranging from 15.9% to 49.5%), 45 has been widely reported in association with worse clinical outcomes in patients with cardiovascular events. The cause of this phenomenon is known to be multifactorial because it seems to be dependent on several issues: choice of assay and cutoff value, 6 timing of testing, pharmacokinetic, drugdrug interactions, comorbidities, age, genetic polymorphisms, and poor compliance.…”