Background and Purpose—The relationship between high plasma 20-hydroxyeicosatetraenoic acid (20-HETE) levels and neurological deterioration (ND) has not been investigated in patients with acute minor ischemic stroke. Method—We conducted a prospective, multicenter observational study in patients with acute minor ischemic stroke. Plasma levels of 20-HETE were measured at admission in all patients. The primary end point of the study was ND within 10 days after admission. The degree of disability was assessed using modified Rankin scale at 3 months after admission. Results—A total of 322 patients were enrolled, of which 85 patients (26.4%) developed ND. Mean 20-HETE level was 1687±158 pmol/L. On multivariate analyses, high level (>1675 pmol/L) of 20-HETE was an independent predictor of ND (third and fourth quartiles). Neurological deterioration was associated with a higher risk of poor outcome (modified Rankin scale scores 3–6) at 3 months. Conclusions—ND is fairly common in acute minor ischemic stroke and is associated with poor prognosis. Elevated plasma level of 20-HETE may be a predictor for ND in acute minor ischemic stroke.

Clopidogrel is an antiplatelet drug primarily used to treat or prevent acute ischemic stroke (IS) or myocardial infarction (MI). This prodrug requires biotransformation to an active metabolite by cytochrome P450 (CYP) enzymes, and CYP single nucleotide polymorphisms (SNPs) could affect the efficiency of such biotransformation. A total of 375 consecutive IS patients were genotyped for eight CYP SNPs using mass spectrometry. Platelet aggregation activity was measured before and after the 7-10 day treatment. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients received clopidogrel therapy and were followed up for six months. Primary outcomes were evaluated as a composite of recurrent ischemic stroke (RIS), MI, and death. The secondary outcome was the modified Rankin Scale (mRS). Clopidogrel resistance occurred in 153 patients (40.8%). The frequency of CYP3A5 (rs776746) GG/AG and CYP2C19*2 (rs4244285) AA/AG genotypes was significantly higher in clopidogrel-resistant patients than in sensitive patients. There was a significant gene-gene interaction between CYP3A5 (rs776746) and CYP2C19*2 (rs4244285). CYP2C19*2 AA and its interaction with CYP3A5 GG were independent predictors of clopidogrel resistance and affected the activity of platelet aggregation. Diabetes mellitus, CYP2C19*2 (rs4244285), clopidogrel resistance, and the interaction of CYP2C19*2 with CYP3A5 were all independent risk factors for the primary outcomes of clopidogrel treatment. Clopidogrel-resistant patients were more likely to have poor outcomes (mRS ＞2 points) compared with clopidogrel-sensitive patients. CYP SNPs and their interactions are associated with drug resistance and outcomes in acute IS patients.

Aims: To evaluate the effects of treatments with clopidogrel plus aspirin (dual therapy) on early neurological deterioration (END) and outcomes at 6 months in patients with acute large artery atherosclerosis (LAA) stroke. Methods: A total of 574 patients with LAA stroke were randomly assigned to receive either dual therapy or aspirin alone (monotherapy). The primary outcome was END. Secondary outcomes included recurrent ischemic stroke (RIS) and outcomes at 6 months. Results: The prevalence of END and RIS was lower in patients on dual therapy than in those on monotherapy during the 30 days. At 6 months, dual therapy improved outcomes among older patients and those with symptomatic stenosis in the posterior circulation and basilar artery. Conclusion: Clopidogrel plus aspirin is superior to aspirin alone for reducing END and RIS within 30 days and improves outcomes in certain subgroups at 6 months.