Acute Minor Stroke Research Articles

Impact of Low Ankle-Brachial Index on the Risk of Recurrent Vascular Events.

Background and Purpose- Low ankle-brachial index (ABI) identifies a stroke subgroup with high risk of recurrent stroke, cardiovascular events, and death. However, limited data exist on the relationship between low ABI and stroke in low and middle-income countries. Therefore, we evaluated the prevalence of ABI ≤0.90 (which is diagnostic of peripheral artery disease) in nonembolic stroke patients or transient ischemic attack and assessed the correlation of low ABI with stroke risk, factors, and recurrent vascular events and death. Methods- Patients ≥45 years with acute transient ischemic attack or minor ischemic strokes were recruited consecutively from over 17 low-income and middle-income countries (Latin America [1543 patients], Middle East [1041 patients], North Africa [834 patients], and South Africa [217 patients]). The ABI measurement was performed at a single visit. Stroke recurrence and risk of new vascular events were assessed after 24 months of follow-up. Results- Among 3487 enrolled patients, abnormal ABI (<0.9) was present in 22.3 %. Patients with an ABI of ≤0.9 were more likely ( P<0.05) to be male, older, and have a history of peripheral artery disease, hypertension, and diabetes mellitus. During 2-year follow-up, the rate of major cardiovascular event was higher in patients with ABI <0.9 than those with ABI ≥0.9 (Kaplan-Meier estimates, 22.5%; 95% CI, 19.6-25.8 versus 13.7%; 21.4-15.1; P<0.001), and when ABI was categorized into 4 groups (≤0.6; 95% CI, 0.6-0.9; 0.9-1; 1-1.4), the rate of major cardiovascular event was higher in those with ABI ≤0.6 than the other groups (Kaplan-Meier estimates, 32.6%; 95% CI, 21.0-48.3 for ABI≤0.6 versus 21.7%; 95% CI, 18.8-25.0 for ABI 0.6-0.9 versus 14.3%; 95% CI, 12.4-16.6 for ABI 0.9-1 versus 13.3%; 95% CI, 11.6-15.2 for ABI 1-1.4; P<0.001). Conclusions- Among patients with nonembolic ischemic stroke or transient ischemic attack, those with low ABI had a higher rate of vascular events and death in this population. Screening for ABI in stroke patients may help identify patients at high risk of future events.

Comparison of administration of clopidogrel with aspirin versus aspirin alone in prevention of secondary stroke after transient ischemic attack

BackgroundPatients with transient ischemic attack (TIA) or minor stroke are at risk of strokes. One of the precautionary measures to reduce risk of stroke in these patients is administration of antiplatelet drugs.MethodsThe aim of this study was comparison of clopidogrel with aspirin versus aspirin alone in prevention of stroke following TIA or acute minor stroke. This clinical trial study was carried out in Farshchian Hospital, Hamadan, Iran in 2018. Fifty-four patients with TIA, isolated visual attacks, and minor stroke were randomly assigned to receive aspirin 80 mg/day or aspirin 80 mg/day and clopidogrel 75 mg/day for 3 months.ResultsAfter this period, patients were examined for occurrence of myocardial stroke, hemorrhagic/ischemic stroke and drug complications. Ischemic stroke or TIA occurred in 5 (18.5%) patients in clopidogrel–aspirin group and 10 patients (37.1%) in aspirin group (P = 0.12).ConclusionThe study suggests a trend toward superiority of administration of clopidogrel with aspirin versus aspirin alone in protection against secondary stroke. Studies in larger cohorts of patients are needed to verify these results.

Pharmacoeconomic evaluation of dual antiplatelet therapy in acute minor ischemic stroke

Aim. To make a pharmacoeconomic assessment of dual antiplatelet therapy (DAPT) in acute minor ischemic stroke by cost-effectiveness analysis. Materials and methods. The results were obtained using systemic, analytical and comparative, logical and pharmacoeconomic methods and data on therapeutic equivalence or bioequivalence of pharmaceuticals from three sources: the Orange Book (USA), protocols of the Committee for Medicinal Products for Human Use of the European Medicines Agency and the Rx index, the Directory of Equivalence of Pharmaceuticals (Ukraine), the results of systematic review and meta-analysis of DAPT to prevent early recurrent ischemic stroke as well as information on the minimum purchase prices of pharmaceuticals. Results. According to data obtained from the Orange Book (USA), protocols of the Committee for Medicinal Products for Human Use of the European Medicines Agency and the Rx index, the Directory of Equivalence of Pharmaceuticals (Ukraine), a cost-effectiveness index and an incremental indicator of cost-effectiveness were calculated for those antiplatelet pharmaceuticals for which there was information available on therapeutic equivalence and bioequivalence, since otherwise the extrapolation of the results of the clinical effectiveness of the original pharmaceuticals for generic drugs would not have been appropriate. Conclusions. Based on data from the Orange Book (USA), protocols of the Committee for Medicinal Products for Human Use of the European Medicines Agency and the Rx index, the Directory of Equivalence of Pharmaceuticals (Ukraine), information on the equivalence of registered pharmaceuticals inUkraine such as Clopidogrel and Acetylsalicylic Acid (ASA) was systematized. Through pharmacoeconomic analysis it was established that as of July 2018: Clinical and economical advantage was observed for application of monotherapy in acute minor ischemic stroke with a use of a generic (Acecor Cardio, 100 mg, Intestine Soluble Tablets, Pharmaceutical company Microkhim Ltd., Ukraine) compared to the original pharmaceutical (Aspirin Cardio, 100 mg, Film-coated Intestine Soluble Tablets, Bayer AG, Germany); the need for additional involvement of small funds is inherent in 10 out of 11 combinations of more effective and more expensive DAPT of acute minor ischemic stroke (Clopidogrel + ASA). It ranges from 14.49 UAH per unit of effectiveness (Trombonet, 75 mg, Film-coated Tablets № 60, Farmak JSC, Ukraine + ASA ) to 29.91 UAH per unit of effectiveness (Clopidogrel Zentiva, 75 mg, Film-coated Tablets № 30, Zentiva, Czech Republic + ASA); for CoPlavix, a combination pharmaceutical (Intestinal Soluble Tablets, 75 mg/75 mg, № 28, Sanofi Winthrop Industrie, France) compared with four ASA pharmaceuticals the incremental cost-effectiveness ratio is the lowest, although still significant (185.77 UAH per unit of effectiveness); this is typical in comparison to Aspirin Cardio (100 mg, Film-coated Intestinal Soluble Tablets № 28, Bayer AG, Germany).

Early Identification of High-Risk TIA or Minor Stroke Using Artificial Neural Network.

Background and Purpose: The risk of recurrent stroke following a transient ischemic attack (TIA) or minor stroke is high, despite of a significant reduction in the past decade. In this study, we investigated the feasibility of using artificial neural network (ANN) for risk stratification of TIA or minor stroke patients.Methods: Consecutive patients with acute TIA or minor ischemic stroke presenting at a tertiary hospital during a 2-year period were recruited. We collected demographics, clinical and imaging data at baseline. The primary outcome was recurrent ischemic stroke within 1 year. We developed ANN models to predict the primary outcome. We randomly down-sampled patients without a primary outcome to 1:1 match with those with a primary outcome to mitigate data imbalance. We used a 5-fold cross-validation approach to train and test the ANN models to avoid overfitting. We employed 19 independent variables at baseline as the input neurons in the ANN models, using a learning algorithm based on backpropagation to minimize the loss function. We obtained the sensitivity, specificity, accuracy and the c statistic of each ANN model from the 5 rounds of cross-validation and compared that of support vector machine (SVM) and Naïve Bayes classifier in risk stratification of the patients.Results: A total of 451 acute TIA or minor stroke patients were enrolled. Forty (8.9%) patients had a recurrent ischemic stroke within 1 year. Another 40 patients were randomly selected from those with no recurrent stroke, so that data from 80 patients in total were used for 5 rounds of training and testing of ANN models. The median sensitivity, specificity, accuracy and c statistic of the ANN models to predict recurrent stroke at 1 year was 75%, 75%, 75%, and 0.77, respectively. ANN model outperformed SVM and Naïve Bayes classifier in our dataset for predicting relapse after TIA or minor stroke.Conclusion: This pilot study indicated that ANN may yield a novel and effective method in risk stratification of TIA and minor stroke. Further studies are warranted for verification and improvement of the current ANN model.

Therapeutic Challenges in Patients With Noncardioembolic Acute Ischemic Stroke in Need of Double Antiplatelet Therapy for Coronary Artery Disease.

The risk of ischemic stroke (IS) is significant within 6-12 months from the myocardial revascularization for an acute cardiac event. Consequently, we can expect to have patients with an acute IS occurring right in the time frame of dual antiplatelet therapy (DAPT) imposed by the coronary heart disease (CHD). Until present, there are no evidence-based guidelines for the management of patients with acute IS in need of DAPT for ischemic heart disease. The aim of this article was to go through the available data and to depict the appropriate therapeutic strategy for this category of patients. We have performed a systematic review of the literature through June 2018, using Medline/PubMed database. DAPT (aspirin and only clopidogrel among all P2Y12 inhibitors) might be maintained or initiated for CHD in patients with minor acute stroke and high-risk transient ischemic attack patient with IS attributable to an important intracranial stenosis, as long as this drug combination proved to be safe for them in the prevention of stroke recurrence. In patients with IS receiving thrombolysis, with increased size of infarction or high National Institute of Health Stroke Score (NIHSS), the risk of hemorrhagic transformation under DAPT must be weighed against the risk of stent thrombosis in the coronary arteries, which, on its turn, depends on the clinical form for which myocardial revascularization was performed, the time interval from the complexity of a certain interventional procedure. In the acute phase of an IS, maintenance or initiation of DAPT therapy imposed by CHD relies, on one hand, on the risk of hemorrhagic transformation of the brain injury and, on the other hand, on the risk of stent thrombosis in the coronary arteries. The management of these patients must be carried on by a vascular team, on an individualized basis.

Abstract TP560: Cognitive Impairment Should Be an Independent Predictor of Poor Functional Outcome in Acute Minor Stroke

Objective: The evaluation of cognitive status is not routine in the acute stroke setting. The aim of the study was to elucidate the association between cognitive function and functional outcome in acute minor ischemic stroke patients. Methods: From December 2016 to November 2017, patients with acute minor ischemic stroke (prehospital modified Rankin Scale (mRS) ≤1 and National Institute of Health Stroke Scale (NIHSS) score ≤3) who were admitted to our department were prospectively analyzed. Prestroke cognitive state was estimated by Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) which was completed by the patient’s relative at the time of admission. Cognitive performance was measured using the Japanese version of Montreal Cognitive Assessment (MoCA-J) within the first 7 days of admission. Cognitive impairment was defined as MoCA-J &lt;23. Functional outcomes were assessed using the mRS at the time of discharge. A poor discharge outcome was defined as an mRS score of 3-5 or death (mRS score of 6). The impacts of cognitive function on outcome were assessed by multivariate logistic regression analyses. Results: Overall, 581 consecutive patients with acute ischemic stroke admitted to our department during the study period. Finally, 128 patients with minor ischemic stroke (median age 72years) were enrolled. In total, 74 (58%) patients had impaired cognitive impairment in the acute phase. Age ( P = 0.0161), NIHSS score on admission ( P &lt;0.0001), IQCODE ( P =0.0167), Moca-J ( P &lt;0.0001), dyslipidemia ( P =0.0101), and sex ( P =0.0222) were different between good and poor outcome. Multivariate analysis showed that high NIHSS score (odds ratio [OR], 7.30; 95% confidence interval [CI], 2.33-39.95, P &lt; 0.0001) upon admission as well as low Moca-J score (OR, 1.32; 95% CI, 1.11-1.61, P = 0.0006) was independently associated with poor functional outcome. Conclusion: Cognitive impairment in acute minor ischemic stroke was common and independently associated with poor functional outcome after adjusting for the effects of stroke severity, prestroke cognitive status, and various risk factors.

Abstract TP14: Predictors of Neurological Worsening Among Patients Presenting With Large Vessel Occlusions and Mild Symptoms

Introduction: We aim to evaluate the predictors of poor neurological outcome among patients presenting with large vessel occlusion (LVO) and mild symptoms who did not undergo upfront thrombectomy. Methods: Single-center retrospective study of consecutive patients with NIHSS≤5 and LVO on CT/MR angiography within 24h from symptom onset and baseline modified rankin score (mRS)0-2 from Jan 2014-Dec 2017. Acute neurologic deterioration definition: change in NIHSS≥4 within 24h. Primary outcome: NIHSS shift ≥4 (discharge NIHSS minus admission NIHSS score). Results: Among 1156 patients with acute minor strokes, 134 (11%) met criteria. 78% underwent CTA/22% MRA, performed &lt;4h of arrival in 83%. Median age was 64[53-71]years, 58% were male, and last-normal-to-hospital-arrival was 5[2- 8]h. Median baseline NIHSS 3[1- 4] and initial systolic blood pressure 161[137-177]mmHg. Median glucose was 114[100- 143]mg/dL, ejection fraction 55[52- 60]%, and NCCT ASPECTS 10[9-10]. Occlusion site was intracranial carotid in 10%, middle cerebral M1 30%, M2 26%, M3 9%, anterior cerebral 3%, extracranial carotid 11%, basilar 7%, and posterior cerebral 2%. RAPID CT perfusion was performed in 42%, with median core 0[0-5]cc, Tmax&gt;4s 152[62-232]cc, Tmax&gt;6s 57[25-108]cc, Tmax&gt;10s 10[0-33]cc. Orthostatic challenge was performed in 28 (21%) with NIHSS worsening ≥1 in 46%. Twenty-four (18%) patients had acute neurological deterioration of NIHSS≥4 at a median of 2[1-16] hours from arrival. Median discharge NIHSS was 2[0- 4] and the NIHSS shift -1[-3- 0]. Etiology was cryptogenic in 24%, cardioembolic in 25%, and large vessel atherosclerosis in 26%. Parenchymal hematomas occurred in 7%. Overall, 22% had an unfavorable NIHSS shift ≥1, 15% NIHSS≥2, and 11% had NIHSS shift≥4. At discharge, only 62% were independent (22% mRS0, 27% mRS1, 12% mRS2). Multivariable regression indicated acute neurological deterioration (OR 7.9; 96%CI 1.4-41.9;p=0.01) and discharge mRS (OR 3.6; 96%CI 1.6-8.4;p=0.01) independently associated with NIHSS shift ≥4. Conclusion: Acute neurological worsening occurs early and predicts an NIHSS shift≥4 at discharge, which in turn is associated with worse discharge mRS. The optimal therapeutic window in LVO with mild NIHSS may be relatively narrow.

Abstract TMP24: No Rebound Effect After Clopidogrel Discontinuation in Patients With Acute Transient Ischemic Attack or Minor Stroke: Subanalysis of the CHANCE Trial

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.

Abstract TMP94: Oxidized Low-Density Lipoprotein and Low-Density Lipoprotein Have Combined Utility in Predicting Outcomes of Minor Stroke and TIA

Objective: To estimate the association of different combination of circulating LDL and oxLDL levels with the outcomes of acute minor ischemic stroke and transient ischemic attack (TIA). Methods: In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, a subgroup of 3019 patients with elevated baseline oxLDL and LDL levels were analyzed. Patients were divided into four groups according to different combination of LDL and oxLDL levels. The associations of LDL and oxLDL with prognosis of patients using multivariable Cox regression models. Results: Among 3019 patients included in this study, the median (interquartile range) of oxLDL, and LDL were 13.96 (6.65-28.81) ug/dL, 3.1(2.5-3.8) mmol/L, respectively. Compared with those with low LDL and oxLDL levels (LDL &lt; 3.37mmol/L with oxLDL &lt;13.96 ug/dL), patients with conformably high levels of LDL and oxLDL (LDL ≥3.37mmol/L , oxLDL ≥13.96 ug/dL) were associated with an increased risk of recurrent stroke at 90 days(HR,1.88; 95% CI,1.37-2.57)) and 1 year (HR,1.71; 95% CI,1.29-2.27). Neither elevated level of oxLDL or LDL increased alone showed statistical significance. Similar results were observed for poor functional outcome. Conclusions: Presence of both elevated oxLDL and LDL levels can predict an increased risk of recurrent stroke and poor functional outcome in minor stroke or high- risk TIA patients. The presence of both oxLDL and LDL might have a combined effect.

Dual Antiplatelet Therapy for Acute TIA or Minor Stroke: Clarifying the Benefits

The Platelet-Oriented Inhibition in New TIA and minor ischemic stroke (POINT) trial was published earlier this year and showed benefit with the use of

Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis

ObjectiveTo assess the effectiveness and safety of dual agent antiplatelet therapy combining clopidogrel and aspirin to prevent recurrent thrombotic and bleeding events compared with aspirin alone in patients with acute...

Comparative Effectiveness of Aspirin and Clopidogrel Versus Aspirin in Acute Minor Stroke or Transient Ischemic Attack.

Background and Purpose- This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel-aspirin to that of aspirin monotherapy in patients with acute minor cerebral ischemia using a prospective, nationwide, multicenter, stroke registry database in South Korea. Methods- CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events)-like patients who met eligibility criteria modeled on the CHANCE trial eligibility criteria, including (1) acute minor ischemic stroke defined as National Institutes of Health Stroke Scale score ≤3 or lesion positive transient ischemic attack within 24 hours of onset and (2) noncardioembolic stroke mechanism. Propensity scores using the inverse probability of treatment weighting was used to adjust for baseline imbalances. The primary outcome was the composite of all stroke (ischemic and hemorrhagic), myocardial infarction, and vascular death by 3 months. Results- Among 5590 patients meeting the eligibility criteria, age was 64±13 year and 62.6% were male. Aspirin and combination of clopidogrel-aspirin were administered in 66.1% and 33.9% of patients, respectively. In unadjusted analysis, rates of the 3-month primary vascular event outcome were lower with clopidogrel-aspirin versus aspirin, 9.9% versus 12.2% (hazard ratio, 0.79 [0.67-0.95]). In propensity-weighted Cox proportional hazards regression with robust estimation, clopidogrel-aspirin was associated with a lower risk of the primary vascular event outcome (hazard ratio, 0.76 [0.63-0.92]) and all stroke events (hazard ratio, 0.74 [0.61-0.90]). Among 6 predefined subgroup analyses, 3 showed potential modification of treatment effect, with lesser benefit associated with the absence of prior antiplatelet use (Pinteraction=0.01) and younger age (<75 years, Pinteraction=0.07), and absence of benefit associated with small vessel occlusion subtype (Pinteraction=0.08). Conclusions- Dual antiplatelet therapy with aspirin and clopidogrel was associated with reduced stroke, myocardial infarction, and vascular death in the 3 months following a presenting minor, noncardioembolic ischemic stroke. Benefits may be particularly magnified in patients with a history of prior antiplatelet therapy, older age, and nonsmall vessel disease stroke mechanism.

The association of lipid profile and bleeding in patients with minor stroke or transient ischemic attack on antiplatelet therapy: subgroup analysis of CHANCE

Objective: Abnormalities of lipid profile were considered as risk factors of hemorrhage after ischemic stroke. We aimed to determine the relationship between lipid levels and bleeding in minor stroke or transient ischemic attack (TIA) patients receiving antiplatelet therapy. Methods: Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride were tested in a subgroup of 3 044 consecutive patients from Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Patients were randomized to clopidogrel plus aspirin group or single aspirin group. The primary endpoint was any bleeding within 90 days. The secondary endpoint was severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition. Cox proportional hazards models were used to assess the associations of lipid levels and outcomes. Results: A total of 59 (1.9%) bleeding events occurred at 90 days. High-density lipoprotein cholesterol (adjusted HR=2.16; 95%CI 1.17-4.00, P=0.014) and age (adjusted HR=1.04; 95%CI 1.01-1.06, P=0.006) were significantly associated with any bleeding. High-density lipoprotein cholesterol was also associated with severe bleeding (adjusted HR=3.05; 95%CI 1.39-6.68, per 1 mmol/L increase). No correlations between outcomes and levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were found. There was no interaction of any lipid component level with randomized antiplatelet therapy. Conclusions: Elevated high-density lipoprotein cholesterol is independently associated with any bleeding and severe bleeding in the patients with acute minor stroke or high-risk TIA on antiplatelet therapy.

Utilizing the Time Trade-Off, Standard Gamble, and Willingness to Pay Utility Measures to Evaluate Health-Related Quality of Life Prior to Knee or Hip Arthroplasty

BackgroundTime trade-off, standard gamble, and willingness to pay assess the number of years, risk of death, and income a patient would give up for perfect health. These questions were used to evaluate the impact knee arthritis, hip arthritis, or failed total knee (TKA) or hip arthroplasty (THA) has on patients’ health-related quality of life prior to surgery. MethodsThree hundred sixty patients including 176 undergoing primary TKA, 127 undergoing primary THA, 31 undergoing revision TKA, and 26 undergoing revision THA were assessed. Time trade-off and standard gamble were converted to utility scores with 1.0 suggesting perfect health and 0 suggesting preference for death rather than living in current state. Willingness to pay is the percentage of yearly income that a patient would pay for perfect health. ResultsThe mean time trade-off, standard gamble, and willingness to pay scores were 0.74, 0.83, and 0.32 without significant difference between procedures with the numbers available for study (P = .16, .31, and 0.41, respectively). Increasing body mass index was correlated with decreasing time trade-off scores (P = .014). ConclusionPatients scheduled for primary or revision THA and TKA would accept an average 17% risk of death, lose 2.6 years of an additional 10-year life expectancy, and pay 32% of their income for perfect health. The time trade-off (0.74) was similar to patients with history of acute myocardial infarction (0.74) or minor stroke (0.72) and worse than those with chronic hepatitis C (0.83) or human immunodeficiency virus/acquired immunodeficiency syndrome infection (0.86). These data highlight the high value that patients place on adult reconstructive procedures.

Canadian Stroke Best Practice Recommendations for Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care, 6th Edition, Update 2018.

The 2018 update of the Canadian Stroke Best Practice Recommendations for Acute Stroke Management, 6th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by healthcare providers and system planners caring for persons with very recent symptoms of acute stroke or transient ischemic attack. The recommendations are intended for use by a interdisciplinary team of clinicians across a wide range of settings and highlight key elements involved in prehospital and Emergency Department care, acute treatments for ischemic stroke, and acute inpatient care. The most notable changes included in this 6th edition are the renaming of the module and its integration of the formerly separate modules on prehospital and emergency care and acute inpatient stroke care. The new module, Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care is now a single, comprehensive module addressing the most important aspects of acute stroke care delivery. Other notable changes include the removal of two sections related to the emergency management of intracerebral hemorrhage and subarachnoid hemorrhage. These topics are covered in a new, dedicated module, to be released later this year. The most significant recommendation updates are for neuroimaging; the extension of the time window for endovascular thrombectomy treatment out to 24 h; considerations for treating a highly selected group of people with stroke of unknown time of onset; and recommendations for dual antiplatelet therapy for a limited duration after acute minor ischemic stroke and transient ischemic attack. This module also emphasizes the need for increased public and healthcare provider's recognition of the signs of stroke and immediate actions to take; the important expanding role of paramedics and all emergency medical services personnel; arriving at a stroke-enabled Emergency Department without delay; and launching local healthcare institution code stroke protocols. Revisions have also been made to the recommendations for the triage and assessment of risk of recurrent stroke after transient ischemic attack/minor stroke and suggested urgency levels for investigations and initiation of management strategies. The goal of this updated guideline is to optimize stroke care across Canada, by reducing practice variations and reducing the gap between current knowledge and clinical practice.

Ticagrelor with Aspirin on Platelet Reactivity in Minor Stroke or Transient Ischemic Attack: A Randomised, Open-Label, Blinded-Endpoint Trial

Background: Previous studies have shown the therapeutic benefits of using ticagrelor, aspirin, or clopidogrel for stroke. However, limited data are available on the safety and efficacy of ticagrelor plus aspirin compared with clopidogrel plus aspirin for treating patients with acute stroke or transient ischemic attack (TIA). Methods: In this randomized, open-label, controlled, blinded-endpoint trial conducted at 26 centers in China, we compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) with clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) for reducing high platelet reactivity (defined as P2Y12 reaction unit>208) in 675 patients with acute minor stroke or TIA during 90 days. Findings: At 90 days, high platelet reactivity occurred in 35 of 280 patients (12.5%) in the ticagrelor/aspirin group and 86 of 290 patients (29.7%) in the clopidogrel/aspirin group (odds ratio [OR], 0.34; 95% confidence intervals [CI], 0.22 to 0.52; P<0.001), and 10.8% versus 35.4% (OR, 0.22, 95% CI, 0.12 to 0.40; P<0.001) of patients carrying CYP2C19 loss-of-function alleles (P=0.04 for interaction). Stroke occurred in 21 of 336 patients (6.3%) in the ticagrelor/aspirin group and 30 of 339 patients (8.8%) in the clopidogrel/aspirin group (hazard ratio, 0.70; 95% CI, 0.40 to 1.22; P=0.20). No difference was observed in the rates of major or minor haemorrhagic events between the ticagrelor and clopidogrel groups (4.8% and 3.5%, respectively; P=0.42). Interpretation: Patients with minor stroke or TIA treated with ticagrelor had a lower rate of high platelet reactivity than those treated with clopidogrel, especially in carriers of the CYP2C19 loss-of-function allele. Funding: Ministry of Science and Technology of the People's Republic of China, Beijing Municipal Science and Technology Commission, Beijing Municipal Commission of Health and Family Planning and AstraZeneca. Declaration of interests: Yilong Wang reports grants from Beijing Municipal Science and Technology Commission and Beijing Municipal Commission of Health and Family Planning. Yongjun Wang reports grants from Ministry of Science and Technology of the People’s Republic of China. Ethical Approval Statement: The PRINCE study protocol and data collection were approved by the ethics committee of Beijing Tiantan Hospital and all of the study centres. An interim analysis was pre-planned in the published protocol. All participants or their representatives provided written consent before being enrolled into the study. The design of the trial was published previously.14 The trial was conducted in accordance with the Declaration of Helsinki.

Abstract WP65: Higher Glucose Level Associated With Unfavorable Outcome in Acute Minor Ischemic Stroke After Thrombolytic Therapy

Introduction: In real world practice, patients with minor stroke symptoms are still treated with thrombolytic therapy and majority of them recover with favorable outcomes at 90 days, but there is room to identify avenues to further enhance their outcomes. We aimed to investigate the risk factors associated with the unfavorable outcome at 90 days after thrombolysis for acute minor ischemic stroke (AMIS). Methods: 152 consecutive patients presented with AMIS (NIHSS ≤3) and received intravenous alteplase between December 2012 and February 2017. Baseline clinic-demographic, characteristics and laboratory tests were recorded. Unfavorable outcome was defined as modified Rankin Scale (mRS) of 2-6 at 90 days. Univariate analysis followed by multivariate analysis was used to identify risk factors for unfavorable outcome. A receiver operating characteristic curve was used to evaluate the predictive value. Results: 113 out of 152 patients (74%) were included in the final analysis, age 59 (53-67), 72.6% men. 32 patients (28.3%) experienced unfavorable outcomes. After adjusting for covariates, only serum glucose level on admission remained an independent factor for unfavorable outcome (OR 1.43, 95% CI: 1.10-2.72, p =0.014), with a 0.617 predictive value for the unfavorable outcome. Conclusions: About 28% of patients with AMIS in this cohort had an unfavorable outcome at 3 months after thrombolysis. Addressing higher serum glucose level on admission may be a viable therapeutic strategy to improve prognoses in these patients.

Association between platelet function and recurrent ischemic vascular events after TIAand minor stroke .

Platelet activation and aggregation play an important role in the pathological and physiological processes of recurrent ischemic vascular events in stroke patients. The purpose of this study is to determine the association between platelet function measured in the acute period and recurrent ischemic vascular events in patients with transient ischemic attack (TIA) or minor stroke. A total of 417 patients who were within the 24-hour period of clopidogrel-aspirin therapy after onset of a minor stroke or high-risk transient ischemic attack according to the Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial were included in this study. The platelet aggregation ratio was detected using a method of continuous platelet counting; patients underwent CYP2C19 genotyping, and the baseline data were recorded. The patients underwent a 6-month follow-up period during which the recurrent ischemic vascular events were observed. Logistic regression analysis was performed to obtain the risk factors for recurrent ischemic vascular events. The number of patients with recurrent ischemic events who had an arachidonic acid-induced maximum platelet aggregation ratio (MAR-AA) (aspirin 100 mg) (31.85 ± 12.86 vs. 26.71 ± 12.44, p=0.007) and adenosine diphosphate-induced maximum platelet aggregation ratio (MAR-ADP) after the administration of 75 mg clopidogrel for 12 ± 2 days (65.82 ± 10.72 vs. 53.10 ± 12.98, p<0.001) was significantly higher compared with the no ischemic vascular event group. Multivariate logistic regression analyses showed that being a carrier of the CYP2C19 loss-of-function (LOF) allele (OR=2.308, 95% CI: 1.087~4.901, p=0.029) as well as the MAR-AA (aspirin 100 mg) (OR=1.028, 95%CI: 1.006 ~ 1.052, p=0.014) and MAR-ADP after the administration of 75 mg clopidogrel (OR=1.067, 95% CI: 1.037~1.095, p<0.001) were risk factors for ischemic vascular events. The MAR-ADP after the administration of 75mg clopidogrel was significantly higher in patients who were carriers of the CYP2C19 (LOF) allele compared with non-carriers (57.53 ± 13.32 vs. 50.86 ± 12.55, p<0.001), and no significant differences between the CYP2C19 LOF allele carriers and non-carriers in the MAR-ADP were detected after the administration of 300 mg clopidogrel (37.18 ± 11.36 vs. 35.86 ± 12.49, p=0.264). Being a carrier of the CYP2C19 LOF allele has a significant influence on clopidogrel response. Platelet function is closely related to recurrent ischemic vascular events in acute minor stroke or TIA patients. .

Different levels of blood pressure, different benefit from dual antiplatelet therapy in minor stroke or TIA patients

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 < 0.001) than mono antiplatelet therapy. And patients with DBP ≥ 90 mmHg, clopidogrel-aspirin significantly reduced the risk of recurrent stroke (HR 0.588, 95% CI 0.463–0.746, p < 0.001), compared with aspirin alone. However, in patients with SBP < 140 mmHg or DBP < 90 mmHg, no significant difference was observed between clopidogrel plus aspirin and aspirin alone. there was no difference in bleeding episodes by treatment assignment across categories of SBP or DBP. Patients with SBP ≥ 140 mmHg or DBP ≥ 90 mmHg after minor stroke or TIA got more benefits from dual antiplatelet therapy. Bleeding risk from dual antiplatelet treatment did not increase among patients with higher BP level on admission.

Dabigatran following acute transient ischemic attack and minor stroke II (DATAS II).

Rationale Patients with transient ischemic attack or minor stroke are at high risk of early recurrent cerebrovascular events. Anticoagulation with heparin or warfarin acutely after ischemic stroke is at least as efficacious as aspirin for preventing recurrent events but is associated with an increased risk of clinical worsening due to hemorrhagic transformation. Aim and hypothesis We aim to demonstrate the safety of early anticoagulation with dabigatran, an oral direct thrombin inhibitor, in acute cerebrovascular syndrome patients. The primary hypothesis is that symptomatic hemorrhagic transformation rates in dabigatran and aspirin-treated patients will be similar. Sample size estimates At least 136 participants in two groups required to demonstrate an absolute between-group difference in the rate of hemorrhagic transformation of 5.6% with 80% power, assuming alpha = 5%. Methods and design A randomized, multicenter open-label clinical trial (NCT02295826). Three-hundred participants with a transient ischemic attack/ischemic stroke (National Institutes of Health Stroke Scale ≤ 9) will undergo magnetic resonance imaging within 72 h of symptom onset and will be randomized to aspirin 81 mg daily or dabigatran 150 mg twice daily for 30 days. Participants undergo repeat magnetic resonance imaging at 30 days and clinical assessment to 90 days. Study outcomes The primary outcome is the symptomatic hemorrhagic transformation rate. Secondary outcomes include recurrent stroke and new ischemic lesions on repeat magnetic resonance imaging. Discussion This study will determine the safety of early anticoagulation with dabigatran in patients with acute transient ischemic attack/ischemic stroke and will inform the design of a phase III randomized trial aimed at demonstrating reduced recurrent early ischemic events after acute transient ischemic attack/stroke.