Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone.In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect.Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of hemorrhagic stroke was 0.3% in each group.Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage. (Funded by the Ministry of Science and Technology of the People's Republic of China; CHANCE ClinicalTrials.gov number, NCT00979589.).
Single small subcortical infarction (SSSI) is an important stroke subtype. The optimal antiplatelet medication for patients with ischemic stroke with an SSSI is still unclear. We aimed to test the efficacy and safety of ticagrelor-aspirin in preventing stroke recurrence among patients with SSSI in the Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial.
Methods
In the CHANCE-2 trial, patients with a minor stroke or TIA who carried CYP2C19 loss-of-function (LOF) alleles were randomly assigned within 24 hours after symptom onset, to either ticagrelor-aspirin (placebo clopidogrel plus a 180 mg loading dose of ticagrelor on day 1, followed by 90 mg twice daily on days 2–90) or clopidogrel-aspirin (placebo ticagrelor plus a 300 mg loading dose of clopidogrel on day 1, followed by 75 mg daily on days 2–90). Aspirin was applied during the first 21 days. Patients who had an SSSI (diffusion-weighted imaging lesion diameter ≤20 mm) were included in this analysis and further categorized into 2 types according to whether they had the responsible intracranial artery stenosis (ICAS): SSSI + ICAS and SSSI − ICAS. The primary efficacy outcome was a new stroke at 90 days.
Results
Among 2,143 eligible patients, 340 had the responsible ICAS, and 1,803 did not. Ticagrelor-aspirin reduced stroke recurrence among all patients with SSSI (hazard ratio [HR]: 0.55; 95% CI 0.38–0.78; p = 0.001) compared with clopidogrel-aspirin. Stroke recurrence occurred in 35/901 (3.9%) patients with SSSI − ICAS on ticagrelor-aspirin and in 72/902 (8.0%) on clopidogrel-aspirin (hazard ratio [HR]: 0.45; 95% CI 0.29–0.68; p < 0.001). In patients with SSSI + ICAS, the corresponding event rates were 14/176 (8.0%) and 13/164 (7.9%), respectively (HR: 1.20; 95% CI 0.45–3.23; p = 0.71; p for interaction = 0.08). The risk of severe or moderate bleeding only occurred in patients with SSSI − ICAS (5/901 [0.6%] vs 5/902 [0.6%]).
Discussion
In this prespecified substudy, ticagrelor-aspirin was superior to clopidogrel-aspirin in reducing the risk of stroke at 90 days among patients with SSSI who carried CYP2C19 LOF allele(s). Although there was no treatment-by-heterogeneous etiology interaction, a greater absolute risk reduction of stroke was observed in patients with SSSI − ICAS than in those with SSSI + ICAS.
Classification of Evidence
This study provides Class II evidence that ticagrelor and aspirin reduced the risk of stroke recurrence compared with clopidogrel with aspirin in adult patients with acute minor SSSI.
Background and Purpose A case-mix adjustment model has been developed and externally validated, demonstrating promise. However, the model has not been thoroughly tested among populations in China. In our study, we evaluated the performance of the model in Chinese patients with acute stroke. Methods The case-mix adjustment model A includes items on age, presence of atrial fibrillation on admission, National Institutes of Health Stroke Severity Scale (NIHSS) score on admission, and stroke type. Model B is similar to Model A but includes only the consciousness component of the NIHSS score. Both model A and B were evaluated to predict 30-day mortality rates in 13,948 patients with acute stroke from the China National Stroke Registry. The discrimination of the models was quantified by c-statistic. Calibration was assessed using Pearson’s correlation coefficient. Results The c-statistic of model A in our external validation cohort was 0.80 (95% confidence interval, 0.79–0.82), and the c-statistic of model B was 0.82 (95% confidence interval, 0.81–0.84). Excellent calibration was reported in the two models with Pearson’s correlation coefficient (0.892 for model A, p<0.001; 0.927 for model B, p = 0.008). Conclusions The case-mix adjustment model could be used to effectively predict 30-day mortality rates in Chinese patients with acute stroke.
To analyze the genetic and clinical characteristics, treatment and prognosis of patients diagnosed with maturity onset of diabetes of the young (MODY) 12 subtype.
Objectives: The combination of clopidogrel and aspirin was superior to aspirin alone in reducing recurrent stroke in patients with acute minor stroke or TIA. Previous studies demonstrated that discontinuation of clopidogrel in patients after ACS was associated with a rebound increase in risk of recurrent events. However, limited data investigated the rebound effect of clopidogrel after discontinuation of clopidogrel therapy in patients with TIA or stroke. Methods: All patients with minor stroke or TIA were recruited from the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Patients who discontinued clopidogrel and switched to aspirin monotherapy during 90 days and 1 year in the clopidogrel plus aspirin arm, and patients who who continued aspirin monotherapy during 90 days and 1 year in the placebo plus aspirin arm were included to our final analysis. The outcomes included risk of recurrent ischemic stroke, recurrent TIA, and composite events during 90 days and 1 year. The prevalence of each outcome was compared between 2 groups for every 30 days. Results: Among 3346 patients included, a total of 34 patients in group who discontinued clopidogrel and switched to aspirin monotherapy presented stroke recurrence, and a total of 42 patients in group continued aspirin monotherapy presented stroke recurrence during the 90 days-1 year period. The inter-group comparisons were not significant, except during day 211 to day 240 (P=0.03). Similar results were found for recurrent ischemic stroke, recurrent TIA, and composite events in these two groups. Conclusions: we found no rebound increase in risk of stroke, ischemic stroke, TIA, and composite events during the 270 days after discontinuation of clopidogrel therapy in patients with TIA or minor stroke.
Small single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and long-term prognoses and the effectiveness of antiplatelet therapy in SSSI.We prospectively enrolled 2890 patients with SSSI from the Third China National Stroke Registry (CNSR-III) database from August 2015 to March 2018. We assessed clinical outcomes and antiplatelet treatment effects in patients with SSSI with and without parent artery stenosis (PAS) identified by magnetic resonance angiography.Among 2890 patients with SSSI in the perforator territory of the middle cerebral artery and the basilar artery, there were 680 (23.53%) patients with PAS and 2210 (76.47%) patients without PAS, respectively. After adjusting for potential confounders, the PAS group had a greater initial stroke severity (OR 1.262, 95% CI 1.058 to 1.505; p=0.0097) and a higher risk of ischaemic stroke recurrence at 3 months (OR 2.266, 95% CI 1.631 to 3.149; p<0.0001) and 1 year (OR 2.054, 95% CI 1.561 to 2.702; p<0.0001), as well as composite vascular events at 3 months (OR 2.306, 95% CI 1.674 to 3.178; p<0.0001) and 1 year (OR 1.983, 95% CI 1.530 to 2.570; p<0.0001), compared with the non-PAS group. In both groups, dual antiplatelet therapy was not superior to single antiplatelet therapy in preventing stroke recurrence, composite vascular events and disability.PAS related to significantly higher rates of short-term and long-term stroke recurrence and composite vascular events, suggesting heterogeneous mechanisms in SSSI subgroups. The effectiveness of antiplatelet therapy for SSSI needs further investigation.
Cognitive impairment usually occurs in the acute phase after stroke, but most stroke survivors experience some form of long-term cognitive deficit. The aim of this study was to establish the cutoff point of the Montreal Cognitive Assessment (MoCA-Beijing) in screening for cognitive impairment (CI) at 6 months of ischemic stroke or transient ischemic attack (TIA).A total of 301 stroke patients and 15 TIA patients were recruited. Patients were assessed at six months by the MoCA-Beijing and a formal neuropsychological battery. The 1.5 SD below the level of the norm on several tests indicated cognitive impairment (CI).Most stroke and TIA patients were in their 60s (61.23 ± 10.60 years old). The optimal cutoff point for MoCA-Beijing in discriminating patients with CI from those with no cognitive impairment (NCI) was 24/25 (sensitivity 63.28%, specificity 71.22%, PPV = 73.68%, NPV = 60.37%, classification accuracy = 66.72%). The predominant cognitive deficits were visuospatial ability (84.85%), and then attention/executive function (79.27%).The MoCA-Beijing cutoff score for differentiating CI from NCI after stroke and TIA at six months was at 24/25, and it is important for routine clinical practice.
Rationale and aim Little is known about the safety and efficacy of the combination of ticagrelor and aspirin in acute ischemic stroke. This study aimed to evaluate whether the combination of ticagrelor and aspirin was superior to that of clopidogrel and aspirin in reducing the 90-day high on-treatment platelet reactivity for acute minor stroke or transient ischemic attack, especially for carriers of cytochrome P450 2C19 loss-of-function allele. Sample size and design This study was designed as a prospective, multicenter, randomized, open-label, active-controlled, and blind-endpoint, phase II b trial. The required sample size was 952 patients. It was registered with ClinicalTrials.gov (NCT02506140). Study outcomes The primary outcome was the proportion of patients with high on-treatment platelet reactivity at 90 days. High on-treatment platelet reactivity is defined as the P2Y12 reaction unit >208 measured using the VerifyNow P2Y12 assay. Conclusion The Platelet Reactivity in Acute Non-disabling Cerebrovascular Events study explored whether ticagrelor combined with aspirin could reduce further the proportion of patients with high on-treatment platelet reactivity at 90 days after acute minor stroke or transient ischemic attack compared with clopidogrel and aspirin.
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