IMPORTANCE Data are limited regarding the association between CYP2C19 genetic variants and clinical outcomes of patients with minor stroke or transient ischemic attack treated with clopidogrel. OBJECTIVE To estimate the association between CYP2C19 genetic variants and clinical outcomes of clopidogrel-treated patients with minor stroke or transient ischemic attack. DESIGN, SETTING, AND PARTICIPANTS Three CYP2C19 major alleles (*2, *3, *17) were genotyped among 2933 Chinese patients from 73 sites who were enrolled in the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) randomized trial conducted from January 2, 2010, to March 20, 2012. INTERVENTIONS Patients with acute minor ischemic stroke or transient ischemic attack in the trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone. MAIN OUTCOMES AND MEASURESThe primary efficacy outcome was new stroke. The secondary efficacy outcome was a composite of new composite vascular events (ischemic stroke, hemorrhagic stroke, myocardial infarction, or vascular death). Bleeding was the safety outcome. RESULTS Among 2933 patients, 1948 (66.4%) were men, with a mean age of 62.4 years. Overall, 1207 patients (41.2%) were noncarriers and 1726 patients (58.8%) were carriers of loss-of-function alleles (*2, *3). After day 90 follow-up, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers but not in the carriers of the loss-of-function alleles (P = .02 for interaction; events among noncarriers, 41 [6.7%] with clopidogrel-aspirin vs 74 [12.4%] with aspirin; hazard ratio [HR], 0.51 [95% CI, 0.35-0.75]; events among carriers, 80 [9.4%] with clopidogrel-aspirin vs 94 [10.8%] with aspirin; HR, 0.93 [95% CI, 0.69 to 1.26]). Similar results were observed for the secondary composite efficacy outcome (noncarriers: 41 [6.7%] with clopidogrel-aspirin vs 75 [12.5%] with aspirin; HR, 0.50 [95% CI, 0.34-0.74]; carriers: 80 [9.4%] with clopidogrel-aspirin vs 95 [10.9%] with aspirin; HR, 0.92 [95% CI, 0.68-1.24]; P = .02 for interaction). The effect of treatment assignment on bleeding did not vary significantly between the carriers and the noncarriers of the loss-of-function alleles (2.3% for carriers and 2.5% for noncarriers in the clopidogrel-aspirin group vs 1.4% for carriers and 1.7% for noncarriers in the aspirin only group; P = .78 for interaction). CONCLUSIONS AND RELEVANCE Among patients with minor ischemic stroke or transient ischemic attack, the use of clopidogrel plus aspirin compared with aspirin alone reduced the risk of a new stroke only in the subgroup of patients who were not carriers of the CYP2C19 loss-of-function alleles. These findings support a role of CYP2C19 genotype in the efficacy of this treatment.

IntroductionSpontaneous intracerebral hemorrhage (ICH) is one of leading causes of mortality and morbidity worldwide. Several predictive models have been developed for ICH; however, none of them have been consistently used in routine clinical practice or clinical research. In the study, we aimed to develop and validate a risk score for predicting 1-year functional outcome after ICH (ICH Functional Outcome Score, ICH-FOS). Furthermore, we compared discrimination of the ICH-FOS and 8 existing ICH scores with regard to 30-day, 3-month, 6-month, and 1-year functional outcome and mortality after ICH.MethodsThe ICH-FOS was developed based on the China National Stroke Registry, in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Poor functional outcome was defined as modified Rankin Scale score (mRS) ≥3 at 1 year after ICH. Multivariable logistic regression was performed to determine independent predictors, and β-coefficients were used to generate scoring system of the ICH-FOS. The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration.ResultsThe overall 1-year poor functional outcome (mRS ≥ 3) was 46.7% and 44.9% in the derivation (n = 1,953) and validation (n = 1,302) cohorts, respectively. A 16-point ICH-FOS was developed from the set of independent predictors of 1-year poor functional outcome after ICH including age (P < 0.001), admission National Institutes of Health Stroke Scale score (P < 0.001), Glasgow Coma Scale score (P < 0.001), blood glucose (P = 0.002), ICH location (P < 0.001), hematoma volume (P < 0.001), and intraventricular extension (P < 0.001). The ICH-FOS showed good discrimination (AUROC) in the derivation (0.836, 95% CI: 0.819-0.854) and validation (0.830, 95% CI: 0.808-0.852) cohorts. The ICH-FOS was well calibrated (Hosmer-Lemeshow test) in the derivation (P = 0.42) and validation (P = 0.39) cohort. When compared to 8 prior ICH scores, the ICH-FOS showed significantly better discrimination with regard to 1-year functional outcome and mortality after ICH (all P < 0.0001). Meanwhile, the ICH-FOS also demonstrated either comparable or significantly better discrimination for poor functional outcome and mortality at 30-day, 3-month, and 6-month after ICH.ConclusionThe ICH-FOS is a valid clinical grading scale for 1-year functional outcome after ICH. Further validation of the ICH-FOS in different populations is needed.

Background and Purpose-The association between hypertension (HTN) and stroke recurrence is unclear, but may be influenced by different subtypes of stroke. This study aims to explore whether HTN contributes to the recurrence of certain subtypes of ischemic stroke (IS). Methods-Data from the China National Stroke Registry was examined and 1-year follow-up data for stroke recurrence was analyzed. Trial of Org 10172 in Acute Stroke Treatment criteria was used to classify the subtypes of all IS. HTN was defined when resting blood pressure was ≥140/90 mm Hg on repeated measurements during hospitalization or a patient had been on antihypertensive medication. Recurrent stroke was defined as a new neurological deficit compatible to IS or intracerebral hemorrhage. The association between HTN and stroke recurrence in patients with different IS subtypes was analyzed by using univariable and multivariable logistic regression models. Results-Of 11 560 patients with IS, 8409 (72.7%) had HTN and 2050 (17.7%) experienced a recurrent stroke within 1 year.Patients with HTN had an insignificantly higher stroke recurrence rate than those without (18.0% versus 17.0%; P=0.21).After stratification by Trial of Org 10172 in Acute Stroke Treatment subtypes, multivariable analysis revealed a significant association between HTN and stroke recurrence in small-artery occlusion subtype (odds ratio, 1.52; 95% confidence interval, 1.03-2.31), but not in the other subtypes (large-artery atherosclerosis: odds ratio, 0.99; 95% confidence interval, 0.81-1.21; cardioembolic: odds ratio, 1.14; 95% confidence interval, 0.75-1.73; other: odds ratio, 0.88; 95% confidence interval, 0.71-1.09). (2) Patients with SAO had one of the traditional clinical lacunar syndromes (including pure motor stroke, pure sensorimotor stroke, pure sensory stroke, ataxic hemiparesis, or clumsy hand dysarthria) and did not have evidence of cerebral cortical dysfunction. Infarct areas were <1.5 cm in diameter on CT or MRI. A history of HTN or diabetes mellitus supports the clinical diagnosis. Evidence of cardiac sources of embolism was absent and large extracranial arteries had a stenosis of <50% in an ipsilateral artery. (3) Patients with CE had at least one cardiac source for an embolus, including rheumatic mitral valve disease, nonvalvular atrial fibrillation, sick sinus syndrome, recent myocardial infarction (<4 weeks), cardiac thrombus, valvular vegetation, akinetic left ventricular segment, atrial myxoma, dilated cardiomyopathy, prosthetic mitral or aortic valve, and paradoxical emboli. Clinical and brain imaging findings are similar to those described for LAA. The angiogram or ultrasonogram does not show significant (≥50%) stenosis or ulcerated plaques in the proximal large-artery supply. (4) Patients with stroke of other determined pathogenesis had rare causes of stroke, including nonatherosclerotic vasculopathies, hypercoagulable states, or hematologic disorders. (5) Stroke of undetermined pathogenesis was defined when any of the following criteria were met: (a) no ca...

Background and Purpose-It remains uncertain whether lower dose intravenous tissue-type plasminogen activator (tPA) for stroke is as effective and safe as the standard dose. Methods-We analyzed data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMSChina). Patients who were treated within 4.5 hours after symptom onset were included. These patients were divided into 5 groups according to tPA doses given: <0.5, 0.5 to 0.7, 0.7 to 0.85, 0.85 to 0.95, and ≥0.95 mg/kg. Symptomatic intracranial hemorrhage, mortality, and 90-day outcome assessed by modified Rankin scale were analyzed. Results-A total of 919 patients were enrolled. Among them, 9 had <0.5 mg/kg, 75 had 0.5 to 0.7 mg/kg, 131 had 0.

Background and purpose High periprocedural complication rate is a key limitation of endovascular treatment of intracranial atherosclerotic disease (ICAD), despite potential risk reduction of recurrent stroke. Taking lessons from the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Arterial Stenosis (SAMMPRIS) trial, targeting a selected patient population, we prospectively evaluated the feasibility and safety of tailored angioplasty and/or stenting for patients with ICAD. Methods From November 2011 to October 2012, 158 patients with symptomatic ICAD caused by hypoperfusion combined with poor collateral flow were consecutively recruited into a prospective single center study. Patients were divided into three groups based on arterial access and lesion morphology: balloon mounted stent group (group BS) for smooth access and Mori A lesion, angioplasty plus self-expanding stent group (group AS) for tortuous access and Mori B or C lesion, and angioplasty group (group AG) for tortuous access and Mori A lesion. The primary endpoints were successful procedure rate and any vascular event within 30 days. Results Overall technical success rate was 96.3% (154/158). There were significant differences in the technical success rate: 89.7% (35/39) in group AG compared with 97.5% (79/81) in group BS and 100% (38/38) in group AS (p=0.042). The 30 day composite stroke, myocardial infarction, or death rate was 4.4% (7/158). Stroke within 30 days occurred in four patients in group BS and in three patients in group AS. Conclusions Individualized treatment of ICAD using tailored devices according to arterial access and lesion morphology was feasible and safe in symptomatic patients caused by hypoperfusion with poor collateral flow.

This study suggests that intravenous rtPA treatment at 3 to 4.5 h of symptom onset remains safe and effective in Chinese patients with AIS.

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Background and PurposeIntracranial Artery Stenosis (ICAS) is one of the most common causes of ischemic stroke in Asia. Previous studies have shown the number of ideal cardiovascular health (CVH) metrics was associated with lower risk of stroke. This study aimed to investigate the relationship between ideal CVH metrics and prevalence of ICAS.MethodsA random sample of 5,412 participants (selected from Kailuan Study as a reference population) aged 40 years or older (40.10% women), free of stroke, transient ischemic attack, and coronary disease, were enrolled in the Asymptomatic Polyvascular Abnormalities Community study from 2010 to 2011. We collected information on the seven CVH metrics (including smoking, body mass index, dietary intake, physical activity, blood pressure, total cholesterol and fasting blood glucose); and assessed ICAS by transcranial Doppler. The relationship between the ideal CVH metrics and prevalence of ICAS was analyzed using the multivariate logistic regression.ResultsAfter adjusting for age, sex, and other potential confounders, the adjusted odds ratios(95% confidence interval) for ICAS were 0.76(0.58–0.99), 0.55(0.43–0.72), 0.49(0.37–0.65), 0.43(0.31–0.61), and 0.36(0.22–0.62), respectively, for those having 2, 3, 4, 5, and 6–7 ideal CVH metrics compared with those having 0–1 ideal metric(p-trend<0.0001). Similar inverse associations were observed in different age and gender groups (all p-trends<0.05).ConclusionWe found a clear gradient relationship between the number of ideal CVH metrics and lower prevalence of ICAS in a Chinese population, which supports the importance of ideal health behaviors and factors in the prevention of ICAS.