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Aims We aimed to validate the predictive value of the ABCD3-I score for short-term and long-term stroke risk after transient ischemic attack (TIA) and to evaluate the influence of symptomatic intracranial artery stenosis (sICAS) on the performance of ABCD3-I. Methods We recruited TIA patients from the Third China National Stroke Registry study. Outcome parameters were stroke events during the 14-day, 3-month, 6-month, and 12-month points. The area under the curve (AUC) was calculated as a measure of predictive ability. A multivariable-adjusted Cox proportional hazards model was used to assess the hazard ratio of risk factors for stroke. Results Among 986 patients, 3.9%, 5.1%, 6.5 %, and 8.2% of participants experienced a stroke event during the 14-day, 3-month, 6-month, and 12-month points post TIA, respectively. The AUCs of ABCD3-I score for the prediction of stroke were 0.786, 0.732, 0.715, and 0.699 at the 14-day, 3-month, 6-month, and 12-month points, respectively. The AUCs were 0.774, 0.690, 0.617, and 0.611 in patients with sICAS, 0.789, 0.748, and 0.758 and 0.734 in those without sICAS. P values of the interaction between ABCD3-I categories and sICAS were 0.0618 for 14-day, 0.0098 for 3-month, 0.0318 for 6-month, and 0.0294 for 12-month. Conclusions ABCD3-I score performed well in predicting short-term risk of a stroke after an index TIA in patients with or without sICAS. However, the predictive power decayed with the prolonged period, and the decayed extent was more pronounced among those with sICAS. The assessment of sICAS is a non-ignorable item when using the ABCD3-I score for long-term stroke risk prediction in patients with TIA.

Background S100A8/A9 is implicated in inflammation mechanisms related to atherosclerosis and plaque vulnerability, but it remains unclear whether S100A8/A9 is associated with the prognosis of ischemic stroke. The aim of this study was to investigate these associations in 2 independent multicenter cohorts. Methods Plasma S100A8/A9 concentrations at baseline were measured among 4785 patients with ischemic stroke from 2 independent cohorts: Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke (IIPAIS) and China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite outcome of death or major disability at 3 months after ischemic stroke. Secondary outcomes were major disability, death, and a composite outcome of death or vascular events. Results Among the combined participants of IIPAIS and CATIS, the adjusted odds ratios associated with the highest quartile of plasma S100A8/A9 were 2.11 (95% CI, 1.66–2.68) for the primary outcome and 1.62 (95% CI, 1.27–2.07) for the secondary outcome of major disability; adjusted hazard ratios were 4.14 (95% CI, 2.10–8.15) for the secondary outcome of death and 2.08 (95% CI, 1.38–3.13) for the composite outcome of death or vascular events. Each SD increase of log-transformed S100A8/A9 was associated with 28% (95% CI, 18%–39%; P Conclusions High plasma S100A8/A9 concentrations at baseline were independently associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that S100A8/A9 might have a role as a prognostic marker of ischemic stroke.

Aim: The impact of international normalized ratio (INR) on prognosis after acute ischemic stroke without anticoagulation therapy is unclear. Herein, the association between baseline INR and stroke outcomes in patients without anticoagulation therapy was investigated. Methods: A total of 14,782 ischemic stroke patients from the China National Stroke Registry II were included in this analysis. The period of follow-up was 1 year after stroke onset. Multivariate logistic regression models were used to estimate the relationship between INR and stroke outcomes including all-cause death, recurrent stroke, composite end point, and poor functional outcome. Results: Of 14,782 patients with stroke, all-cause death occurred in 1080 (7.3%), recurrence stroke in 538 (3.9%), combined end point in 1319 (8.9%), and poor functional outcome in 3001 (20.3%). Compared with the medium INR group (0.9–1.1), the odds ratios with confidence intervals of 95% for the high INR group (> 1.1) were 1.58 (1.32–1.98) for all-cause death, 1.40 (1.10–1.79) for stroke recurrence, 1.52 (1.29–1.79) for combined end point, and 1.21 (1.06–1.39) for poor functional outcome. No association between low INR (< 0.9) and any stroke outcomes was found compared with the medium group. Conclusions: Increased admission INR was associated with adverse stroke outcomes among acute ischemic stroke patients without atrial fibrillation or anticoagulation therapy.

Objective: Serum cystatin C (CysC) is a sensitive marker of renal function to predict cardiovascular diseases. We aimed to investigate the predictive value of CysC for clinical outcomes independent of renal function in patients with acute ischemic stroke (AIS).Methods: We measured serum CysC levels in 10,256 AIS patients from Third China National Stroke Registry (CNSR-III). The primary outcome was a combination of all-cause mortality and major disability (modified Rankin scale score, 3–6). Secondary outcomes included stroke recurrence and combined vascular events at 1 year. Outcomes were analyzed using logistic regression and Cox proportional hazards models, respectively.Results: The median CysC of included patients was 0.95 mg/l (interquartile range, 0.83–1.10 mg/l). A U-shaped association was observed between CysC and primary outcome (all-cause mortality or major disability) [quartile (Q)1 vs. Q2: adjusted odds ratio (aOR) 1.29, 95% CI 1.06–1.58, p = 0.012; Q3 vs. Q2: aOR 1.12, 95% CI 0.93–1.35, p = 0.242; Q4 vs. Q2: aOR 1.35, 95% CI 1.10–1.65, p = 0.004]. A similar trend also existed in “preserved renal function” patients. Adding CysC to a model containing conventional risk factors improved the model performance with integrated discrimination improvement (IDI) of 0.13% (p = 0.016) and net reclassification index (NRI) of 13.10% (p Conclusions: CysC showed a U-shaped correlation with 1-year stroke clinical outcome, suggesting that serum CysC may not only be a simple candidate marker of renal function.

Previous study reported that acute phase systolic blood pressure (BP) trajectories were associated with subsequent clinical outcomes among patients with ischemic stroke. However, the association between discharge systolic BP trajectories and ischemic stroke prognosis is not well characterized. A total of 3479 patients with ischemic stroke with 3 BP measurements after hospital discharge from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) were included in this analysis. Discharge systolic BP trajectories were identified by latent mixture modeling. Study outcomes related to mortality, major disability, recurrent stroke, and cardiovascular events were collected 24 months after stroke onset. Logistic regression and Cox proportional hazards models were used to examine the association of systolic BP trajectories with clinical outcomes during follow-up. We identified 4 discharge systolic BP trajectories: high-stable, high-decreasing, low-increasing, and low-stable. Compared with participants in the high-stable systolic BP trajectory group, those in the high-decreasing and low-stable trajectory groups had a decreased risk of the composite outcome of death or major disability, with multiple-adjusted odds ratios (95% CIs) of 0.56 (0.31–0.97) and 0.50 (0.24–0.89), respectively, and a decreased risk of mortality, with multiple-adjusted hazard ratios (95% CIs) of 0.36 (0.13–0.99) and 0.19 (0.07–0.50), respectively. Patients in the low-stable trajectory group had the lowest risk of recurrent stroke, cardiovascular events, and the composite outcome of death or cardiovascular events. This implicates that patients with a high-decreasing or low-stable systolic BP trajectory after discharge had a lower risk of adverse clinical outcomes among patients with ischemic stroke.

Background and purposeThe association between annual household income and prognosis of ischaemic stroke remains debatable. We aimed to prospectively investigate the relationship between annual household income and prognosis at 3 months after ischaemic stroke.MethodsWe included 3975 participants from the China Antihypertensive Trial in Acute Ischemic Stroke. All participants were categorised into three groups according to annual household income per capita: ResultsWithin 3 months after ischaemic stroke, 1002 participants (25.20%) experienced primary outcome (880 major disabilities and 122 deaths). After multivariate adjustment, low annual household income level was associated with increased risk of the primary outcome (OR 1.60; 95% CI: 1.12 to 2.31; Ptrend=0.034) when two extreme groups were compared. The meta-analysis confirmed the significant association between income level and death or major disability after stroke (pooled relative risk for lowest vs highest income level, 1.31 (95% CI: 1.18 to 1.45)).ConclusionsLow annual household income per capita was significantly associated with increased risks of adverse clinical outcomes at 3 months after ischaemic stroke, independently of established risk factors. Further studies from other samples are needed to replicate our findings due to a reason for excluding some patients who had a severe stroke in this study.Trial registration numberClinicalTrials.gov (http://wwwclinicaltrialsgov) Registry (NCT01840072).

AimCerebrovascular disease is the leading cause of death and disability in China, causing a huge burden among patients and their families. Hence, stroke prevention is critical, especially in the high-risk population. Here, we present the evidence-based guideline suitable for the Chinese population.MethodsLiterature search of PubMed and Cochrane library (from January 1964 to June 2019) was done. After thorough discussion among the writing group members, recommendations were listed and summarised. This guideline was reviewed and discussed by the fellow writing committees of the Chinese Stroke Association’s Stroke.ResultsThis evidence-based guideline was written in three parts: controlling the risk factors of stroke, utilisation of antiplatelet agents and assessing the risks of first-ever stroke. All recommendations were listed along with the recommending classes and levels of evidence.ConclusionsThis guideline provides recommendations for primary prevention of cerebrovascular disease among high-risk population in China. Controlling related risk factors, appropriately using antiplatelet agents, assessing the risk of developing first-ever stroke should help reduce the rate of cerebrovascular disease in China.

BackgroundsEmbolic stroke is one of the main mechanisms of ischaemic stroke. Even if treated with recommended antithrombotic agents, stroke recurrence remains high. The Shuxuetong injection, a purified extract of traditional Chinese medicine widely used for thrombus diseases in clinical practice in China, could be a promising agent to prevent stroke recurrence.AimsTo describe the design of the Shuxuetong injection for prevention of recurrence in acute ischaemic stroke with embolism mechanisms.DesignThe Shuxuetong for Prevention of recurrence in Acute Cerebrovascular events with Embolism (SPACE) trial is a multicentre, randomised, double-blind, placebo-controlled, parallel-group, superiority trial to evaluate the efficacy and safety of Shuxuetong injection in reducing recurrence or silent new ischaemic lesions on patients with acute embolic stroke within 10 days. An estimated 2416 patients with embolic stroke within 72 hours of symptom onset from 80 hospitals will be randomly assigned to one of two groups receiving Shuxuetong injection or placebo injection for 10 days. The primary endpoint is symptomatic or asymptomatic new cerebral infarction within 10 days after randomisation.ConclusionThe SPACE Trial will provide valuable evidence for the efficacy and safety of Shuxuetong injection for the prevention of stroke recurrence in patients with imaging-defined embolic stroke.Clinical trial registrationNCT03090113.

Background Conventional prognostic risk factors can only partly explain the adverse clinical outcomes after ischemic stroke. We aimed to establish a set of prognostic metrics and evaluate its public health significance on the burden of adverse clinical outcomes of ischemic stroke. Methods All patients were from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). We established prognostic metrics of ischemic stroke from 20 potential biomarkers in a propensity-score-matched extreme case sample (n = 146). Pathway analysis was conducted using Ingenuity Pathway Analysis. In the whole CATIS population (n = 3575), we evaluated effectiveness of these prognostic metrics and estimated their population-attributable fractions (PAFs) related to the risk of clinical outcomes. The primary outcome was a composite outcome of death or major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Results Matrix metalloproteinase-9 (MMP-9), S100A8/A9, high-sensitivity C-reactive protein (hsCRP), and growth differentiation factor-15 (GDF-15) were selected as prognostic metrics for ischemic stroke. Pathway analysis showed significant enrichment in inflammation and atherosclerosis signaling. All 4 prognostic metrics were independently associated with poor prognosis of ischemic stroke. Compared with patients having 1 or 0 high-level prognostic metrics, those with 4 had higher risk of primary outcome (OR: 3.84, 95%CI: 2.67–5.51; PAF: 37.4%, 95%CI: 19.5%–52.9%). Conclusion The set of prognostic metrics, enriching in inflammation and atherosclerosis signaling, could effectively predict the prognosis at 3 months after ischemic stroke and would provide additional information for the burden of adverse clinical outcomes among patients with ischemic stroke.

We aimed to assess the association between systolic blood pressure (SBP) and clinical outcome in 2,397 ischemic stroke (IS) or transient ischemic attack (TIA) patients from the Blood Pressure and Clinical Outcome in TIA or Ischemic Stroke (BOSS) study. BOSS study was a hospital-based, prospective cohort study. The SBP was defined as mean value of 90 days self-measured SBP after onset. Cox proportional hazards models were conducted to test the risk of combined vascular events (CVE) and stroke recurrence among different SBP categories. Restricted cubic splines were used to explore the shape of associations between SBP and clinical outcomes. A J-shaped association of SBP with CVE and stroke recurrence within 90 days was observed (P nonlinearity

Background The impact of estimated glomerular filtration rate ( eGFR ) on clinical short‐term outcomes after stroke thrombolysis with tissue plasminogen activator remains controversial. Methods and Results We analyzed 18 320 ischemic stroke patients who received intravenous tissue plasminogen activator at participating hospitals in the Chinese Stroke Center Alliance between June 2015 and November 2017. Multivariate logistic regression models were used to evaluate associations between eGFR (2 ) and in‐hospital mortality and symptomatic intracerebral hemorrhage, adjusting for patient and hospital characteristics and the hospital clustering effect. Of the 18 320 patients receiving tissue plasminogen activator, 601 (3.3%) had an eGFR eGFR 45 to 59, 3679 (20.1%) had an eGFR 60 to 89, and 13 415 (73.2%) had an eGFR ≥90. As compared with eGFR ≥90, eGFR values CI , 2.18–5.91), 45 to 59 (4.0% versus 0.9%, adjusted odds ratio, 2.00; 95% CI , 1.18–3.38), and 60 to 89 (2.5% versus 0.9%, adjusted odds ratio, 1.67; 95% CI , 1.20–2.34) were independently associated with increased odds of in‐hospital mortality. However, there was no statistically significant association between eGFR and symptomatic intracerebral hemorrhage. Conclusions eGFR was associated with an increased risk of in‐hospital mortality in acute ischemic stroke patients after treatment with tissue plasminogen activator. eGFR is an important predictor of poststroke short‐term death but not of symptomatic intracerebral hemorrhage.

Using data from the Blood Pressure and Clinical Outcome in TIA or Ischemic Stroke (BOSS) study, we aim to test the applicability and feasibility of stroke secondary prevention recommendations from the 2017 American College of Cardiology/American Heart Association guideline. Patients were categorized based on their blood pressure (BP) status at 3 months. The nonhypertension group was defined as those without a diagnosis of hypertension. The other patients were further divided into three subgroups according to office BP measured at 3-month visit (BP

Key Points Question Is early antihypertensive therapy associated with different outcomes among patients with ischemic stroke with or without a history of hypertension? Findings In this prespecified subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke randomized clinical trial, early antihypertensive treatment was not associated with different death and major disability outcomes among 4071 patients with ischemic stroke with or without hypertension. However, early antihypertensive therapy was associated with significantly decreased 3-month rates of recurrent stroke among patients with prior hypertension. Meaning These findings suggest that continuing antihypertensive treatment may decrease the risk of recurrent stroke among patients with acute ischemic stroke and prior hypertension, and the decision to decrease blood pressure should be based on individual clinical judgment, requiring caution for those without prior hypertension., Importance Clinical trials have generally shown a neutral effect of early blood pressure (BP) decreases on clinical outcomes after acute ischemic stroke. Whether the effect of early antihypertensive therapy differs for patients with ischemic stroke with or without prior hypertension is unclear. Objective To investigate the association between immediate antihypertensive treatment and patient outcomes according to the presence or absence of hypertension before stroke onset. Design, Setting, and Participants This study was a prespecified subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS), a multicenter, single-blind, blinded end-points randomized clinical trial of 4071 patients with acute ischemic stroke and elevated systolic BP. Patients were recruited from August 2009 to May 2013, and this statistical analysis was performed using the intention-to-treat population from January to October 2018. Interventions Participants were randomly assigned to receive antihypertensive treatment (aimed at decreasing systolic BP by 10%-25% within the first 24 hours after randomization, achieving systolic BP, This prespecified subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) randomized clinical trial evaluates the association between immediate antihypertensive treatment and patient outcomes among patients with acute ischemic stroke with vs without a history of hypertension.

Jie Xu,1,2,* Yi Liu,3,* Yongli Tao,4 Xuewei Xie,1,2 Hongqiu Gu,1,2 Yuesong Pan,1,2 Xingquan Zhao,1,2 Yongjun Wang,1,2 Aoshuang Yan,3 Yilong Wang1,21Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, 2China National Clinical Research Center for Neurological Diseases, 3Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, 4Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China*These authors contributed equally tothis workBackground: The relationship between poststroke blood pressure (BP) and clinical outcomes in ischemic stroke (IS) is still controversial. However, there is no large BP database for IS or transient ischemic attack (TIA) in China. This study aims to describe the rationale, study design, and baseline characteristics of a nationwide BP database in IS or TIA patients in China.Materials and methods: The BOSS (blood pressure and clinical outcome in TIA or ischemic stroke) study was a hospital-based, prospective cohort study aiming to assess BP parameters and clinical outcome in IS/TIA patients. BP parameters were based on office BP, ambulatory BP, and home BP. Clinical outcomes included stroke recurrence, combined vascular events, and disability. Electronic case-report forms were used to record baseline and follow-up data. The patients were followed up for clinical outcomes at 3 months through face-to-face interview and at 12 months by telephone.Results: Between October 2012 and February 2014, the BOSS registry recruited 2,608 patients from 61 hospitals, with a mean age of 62.5 years, 32.4% of whom were female, 88.9% with an entry diagnosis of IS, and 86% diagnosed with hypertension. The rates of patients lost-to-follow-up were 3.1% at 3 months and 5.1% at 1 year; 93% of patients completed ambulatory BP monitoring during hospitalization and 94.7% finished a 3-month BP diary.Conclusion: The BOSS registry will provide important evidence about BP management in the acute phase and secondary prevention for IS/TIA patients. Keywords: blood pressure, ischemic stroke, transient ischemic attack

Background and Purpose: To investigate the association of renal function with in-hospital death and recurrent stroke in patients with acute stroke. Methods: Data were from the Chinese Stroke Center Alliance (CSCA) with a sample of 511 036 patients. Baseline eGFR was calculated with the Chinese modification of CKD-EPI equation and categorized into 4 groups. Logistic regression models with generalized estimating equations were used to evaluate the risks for in-hospital death and recurrent stroke among eGFR categories with and without stratification for hypertension, diabetes mellitus (DM) and atrial fibrillation (AF). A cubic spline smoothing technique was used to interpolate the overall trend of risks through the range of eGFR. Results: Of 501 497 patients, 70.1% had an eGFR ≥90, 21.7% an eGFR 60 to 89, 4.1% an eGFR 45 to 59, 4.1% an eGFR2 . In-hospital death occurred in 3.0% of patients with an eGFR of P =0.001). The other results were almost consistent in stratified analyses by hypertension, DM or AF. There was a J-shaped relationship between eGFR and in-hospital death. A linear relationship was observed between eGFR and recurrent stroke. Conclusions: Low eGFR was associated with increased risk of all-cause mortality but not with recurrent stroke in patient with acute stroke.

Objective— Serum Dkk-1 (dickkopf-1) level has been shown to be elevated in patients with ischemic stroke, but its impact on clinical outcomes of ischemic stroke remains unclear. The aim of this study is to investigate the association between serum Dkk-1 and prognosis of ischemic stroke. Approach and Results— We measured serum Dkk-1 levels in 3178 patients with ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was a combination of all-cause mortality and major disability (modified Rankin scale score, ≥3) at 1 year after stroke. Secondary outcomes were stroke recurrence and vascular events. After multivariate adjustment, elevated Dkk-1 levels were associated with an increased risk of primary outcome (odds ratio, 1.40; 95% CI, 1.03–1.89; P trend =0.015) when 2 extreme quartiles were compared. Each SD increase of log-transformed Dkk-1 was associated with 12% (95% CI, 1%–24%) increased risk of primary outcome. Multiple-adjusted spline regression model showed a linear association between serum Dkk-1 and risk of primary outcome ( P for linearity, 0.039). Subgroup analyses further confirmed these associations. The addition of serum Dkk-1 to conventional risk factors improved the predictive power for primary outcome (net reclassification improvement: 10.11%, P =0.029; integrated discrimination improvement: 0.21%, P =0.028). Conclusions— High serum Dkk-1 levels at baseline were associated with poor prognosis at 1 year after ischemic stroke, suggesting that serum Dkk-1 may be a potential prognostic biomarker for ischemic stroke. Further studies from other samples of patients with ischemic stroke are needed to replicate our findings and to clarify the potential mechanisms.

The study aimed to evaluate whether the benefits of dual antiplatelet therapy would be influenced by blood pressure (BP) levels, among acute minor stroke or transient ischemic attack (TIA). In CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling cerebrovascular Events) trail, Patients were stratified by systolic BP (SBP) and diastolic BP (DBP) level measured on admission, respectively, using the supine position BP within 24 hours after symptoms onset. The primary efficacy outcome was stroke recurrence, bleeding was the safety outcome. Patients with SBP ≥ 140 mmHg, dual antiplatelet treatment could reduce the risk of stroke recurrence significantly (HR 0.654, 95% CI 0.529–0.793, p

Objective Our objective is to compare the predictive accuracy of 4 recently established stroke mortality scores in the Chinese population, including the Get With The Guidelines-Stroke risk score, the iScore prediction rule for 30-day mortality, the iScore prediction rule for 1-year mortality, and the PLAN score. Methods We analyzed data from 9698 hospitalized patients with acute ischemic stroke in the China National Stroke Registry (September 2007–August 2008). Outcome measures were in-hospital mortality, 30-day mortality, and 1-year mortality. To evaluate the performance of each model, we calculated the area under the receiver operating characteristic curve. The areas under the curve (AUCs) were compared using the z -test. Results Among 9698 patients, the mean age was 65.5 years and 38.6% were female. Overall in-hospital mortality, 30-day mortality, and 1-year mortality were 3.0%, 5.9%, and 14.6%, respectively. The AUC values of 4 scores for each outcome were all more than .75. The z -test did not show significant difference among the AUC values of these 4 scores. For patients who received thrombolysis therapy, these 4 scores had apparent reductions in the AUC values. Conclusions We could confirm the predictive value of all these 4 scores for short-term and long-term mortalities in Chinese IS patients. However, these 4 scores need to be interpreted with caution in the patients who received thrombolysis therapy.

The effects of erythropoietin (EPO) on plasticity of nervous synapse in CA1 region of hippocampal of vascular dementia (VaD) rats were studied. The Wistar rats reaching standard were randomly divided into three groups: Sham control group, VaD group, VaD + EPO injection treatment (E) group. The bilateral common carotid arteries of rats were permanently ligated to establish VaD model. Special study and memory were observed by Y-maze test. The expressions relative rate of MAP-2 and SYN in CA1 region of hippocampus at different time were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Immunohistochemistry (ICH). 4, 8 and 12 weeks after operation, there were obvious decrease in MAP-2 and SYN expression in both VaD and E groups, while it was much more for VaD group. EPO could comparatively increase the MAP-2 and SYN protein and mRNA expression in the hippocampal CA1 region of VaD rats. These results suggested that EPO might develop its improvement by regulating the plasticity of nervous synapse, which were in terms of increasing MAP-2 and SYN protein and mRNA expression in the CA1 region of hippocampal of VaD rats. Key words: Erythropoietin, vascular dementia, nervous synapse, MAP-2, SYN.

BackgroundIn patients with a minor ischaemic stroke or transient ischaemic attack (TIA), separate trials have shown that dual antiplatelet therapy with clopidogrel plus aspirin (clopidogrel–aspirin) or ticagrelor plus aspirin (ticagrelor–aspirin) are more effective than aspirin alone in stroke secondary prevention. However, these two sets of combination have not been directly compared. Since clopidogrel was less effective in stroke patients who were CYP2C19 loss-of-function (LOF) allele carriers, whether ticagrelor–aspirin is clinically superior to clopidogrel–aspirin in this subgroup of patients with stroke is unclear.AimTo describe the rationale and design considerations of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE-2) trial.DesignCHANCE-2 is a randomised, double-blind, double-dummy, placebo-controlled, multicentre trial that compares two dual antiplatelet strategies for minor stroke or TIA patients who are CYP2C19 LOF allele carriers: ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily on days 2–90) or clopidogrel (300 mg loading dose on day 1 followed by 75 mg daily on days 2–90), plus open-label aspirin with a dose of 75–300 mg on day 1 followed by 75 mg daily on day 2–21. All will be followed for 1 year.Study outcomesThe primary efficacy outcome is any stroke (ischaemic or haemorrhagic) within 3 months and the primary safety outcome is any severe or moderate bleeding event within 3 months.DiscussionThe CHANCE-2 trial will evaluate whether ticagrelor–aspirin is superior to clopidogrel–aspirin for minor stroke or TIA patients who are CYP2C19 LOF allele carriers.Trial registration numberNCT04078737.

BackgroundsIncreased blood pressure (BP) for patients who had an acute ischaemic stroke is associated with poor functional outcome, however the optimal timing of antihypertensive therapy is unknown.AimsWe aim to compare early antihypertensive treatment to delayed antihypertensive treatment for reducing the risk of composite major disability and mortality at 3 months in acute ischaemic stroke.DesignThe China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) trial is a multicentre, randomised, open-label, blinded-endpoints trial that will be conducted in 100 hospitals in China. The primary outcome is the composite of death and major disability (modified Rankin Scale score ≥3) at 3 months of randomisation. Antihypertensive treatment will be received immediately after randomisation in the early treatment group, aimed at average systolic BP by 10%–20% reduction within the first 24 hours, and achieving an average BP level of ConclusionThe CATIS-2 trial will be testing the hypotheses that early BP lowering leads to improved functional outcome without any other harms, and developing clinical guidelines of the BP management for patients who had an acute ischaemic stroke.Trial registration numberNCT03479554.