Prospective Validation of Computed Tomography to Identify Patients at High Risk for Stroke After Transient Ischemic Attack or Minor Stroke.

BACKGROUND: Computed tomography (CT) findings of acute and chronic ischemia are associated with subsequent stroke risk in patients with transient ischemic attack. We sought to validate these associations in a large prospective cohort of patients with transient ischemic attack or minor stroke. METHODS: This prospective cohort study enrolled emergency department patients from 13 hospitals with transient ischemic attack who had CT imaging. Primary outcome was stroke within 90 days. Secondary outcomes were stroke within 2 or 7 days. CT findings were abstracted from radiology reports and classified for the presence of acute ischemia, chronic ischemia, or microangiopathy. Multivariable logistic regression was used to test associations with primary and secondary end points. RESULTS: From 8670 prospectively enrolled patients between May 2010 and May 2017, 8382 had a CT within 24 hours. From this total population, 4547 (54%) patients had evidence of acute ischemia, chronic ischemia, or microangiopathy on CT, of whom 175 had a subsequent stroke within 90 days (3.8% subsequent stroke rate; adjusted odds ratio [aOR], 2.33 [95% CI, 1.62-3.36]). This was in comparison to those with CT imaging without ischemia. Findings associated with an increased risk of stroke at 90 days were isolated acute ischemia (6.0%; aOR, 2.42 [95% CI, 1.03-5.66]), acute ischemia with microangiopathy (10.7%; aOR, 3.34 [95% CI, 1.57-7.14]), chronic ischemia with microangiopathy (5.2%; aOR, 1.83 [95% CI, 1.34-2.50]), and acute ischemia with chronic ischemia and microangiopathy (10.9%; aOR, 3.49 [95% CI, 1.54-7.91]). Acute ischemia with chronic ischemia and microangiopathy were most strongly associated with subsequent stroke within 2 days (aOR, 4.36 [95% CI, 1.31-14.54]) and 7 days (aOR, 4.50 [95% CI, 1.73-11.69]). CONCLUSIONS: In patients with transient ischemic attack or minor stroke, CT evidence of acute ischemia with chronic ischemia or microangiopathy significantly increases the risk of subsequent stroke within 90 days of index visit. The combination of all 3 findings results in the greatest early risk.

Long-Term Results of Stenting versus Endarterectomy for Carotid-Artery Stenosis.

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial, we found no significant difference between the stenting group and the endarterectomy group with respect to the primary composite end point of stroke, myocardial infarction, or death during the periprocedural period or any subsequent ipsilateral stroke during 4 years of follow-up. We now extend the results to 10 years. METHODS: Among patients with carotid-artery stenosis who had been randomly assigned to stenting or endarterectomy, we evaluated outcomes every 6 months for up to 10 years at 117 centers. In addition to assessing the primary composite end point, we assessed the primary end point for the long-term extension study, which was ipsilateral stroke after the periprocedural period. RESULTS: Among 2502 patients, there was no significant difference in the rate of the primary composite end point between the stenting group (11.8%; 95% confidence interval [CI], 9.1 to 14.8) and the endarterectomy group (9.9%; 95% CI, 7.9 to 12.2) over 10 years of follow-up (hazard ratio, 1.10; 95% CI, 0.83 to 1.44). With respect to the primary long-term end point, postprocedural ipsilateral stroke over the 10-year follow-up occurred in 6.9% (95% CI, 4.4 to 9.7) of the patients in the stenting group and in 5.6% (95% CI, 3.7 to 7.6) of those in the endarterectomy group; the rates did not differ significantly between the groups (hazard ratio, 0.99; 95% CI, 0.64 to 1.52). No significant between-group differences with respect to either end point were detected when symptomatic patients and asymptomatic patients were analyzed separately. CONCLUSIONS: Over 10 years of follow-up, we did not find a significant difference between patients who underwent stenting and those who underwent endarterectomy with respect to the risk of periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke. The rate of postprocedural ipsilateral stroke also did not differ between groups. (Funded by the National Institutes of Health and Abbott Vascular Solutions; CREST ClinicalTrials.gov number, NCT00004732.).

Influence of multiple stents on periprocedural stroke after carotid artery stenting in the Carotid Revascularization Endarterectomy versus Stent Trial (CREST).

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stent Trial (CREST), carotid artery atherosclerotic lesion length and nature of the lesions were important factors that predicted the observed difference in stroke rates between carotid endarterectomy and carotid artery stenting (CAS). Additional patient-related factors influencing CAS outcomes in CREST included age and symptomatic status. The importance of the operator's proficiency and its influence on periprocedural complications have not been well defined. We evaluated data from CREST to determine the impact of use of multiple stents, which we speculate may be related to technical proficiency. METHODS: CREST includes CAS performed for symptomatic ≥50% carotid stenosis and asymptomatic ≥70% stenosis. Both symptomatic and asymptomatic patients were enrolled in the trial and in the lead-in registry. Data from patients enrolled in the CREST registry and randomized trial from 2000 to 2008 were reviewed for patient- and lesion-related characteristics along with number of stents deployed. The occurrence of 30-day stroke and demographic and clinical features were recorded. Odds ratios for 30-day stroke associated with the use of multiple stents were calculated in univariate analysis and on multivariable analysis after adjustment for demographics (age, sex, symptomatic status), lesion characteristics (length, ulceration, eccentric, percentage stenosis), and risk factors (diabetes, hypertension, dyslipidemia, and smoking). RESULTS: The registry (n = 1531) and trial (n = 1121) enrolled 2652 patients undergoing CAS. The mean age was 69 years; 36% were women, and 38% were symptomatic. The mean diameter stenosis was 78%, and the mean lesion length was 18 mm (±standard deviation, 8 mm). Risk factors included hypertension (85%), diabetes (32%), dyslipidemia (84%), and smoking (23%). All patients received Acculink stents (Abbott Vascular, Abbott Park, Ill) that were 20, 30, or 40 mm in length (straight or tapered) and Accunet (Abbot Vascular) embolic protection when possible. Most patients received one stent (n = 2545), whereas 98 patients received two stents and 9 patients received three stents (P < .001) to treat the lesion. Patients receiving more than one stent were older (P = .01) but did not differ in other demographic or risk factors. Strokes occurred in 118 (4.5%) of all CAS procedures, in 102 (4%) with the use of one stent, and in 16 (15%) with the use of two or three stents. After adjustment for demographics, lesion characteristics, and risk factors, the use of more than one stent resulted in 2.90 odds (95% confidence interval, 1.49-5.64) for a stroke. CONCLUSIONS: Although we know that lesion characteristics (length, ulceration) play an important role in CAS outcomes, in this early experience with carotid stenting, a significant and independent relationship existed between the number of stents used and procedural risk of CAS. We postulate that this was an indicator of the operator's inexperience with the procedure.

Computed tomography identifies patients at high risk for stroke after transient ischemic attack/nondisabling stroke: prospective, multicenter cohort study.

BACKGROUND AND PURPOSE: Ischemia on computed tomography (CT) is associated with subsequent stroke after transient ischemic attack. This study assessed CT findings of acute ischemia, chronic ischemia, or microangiopathy for predicting subsequent stroke after transient ischemic attack. METHODS: This prospective cohort study enrolled patients with transient ischemic attack or nondisabling stroke that had CT scanning within 24 hours. Primary outcome was subsequent stroke within 90 days. Secondary outcomes were stroke at ≤2 or >2 days. CT findings were classified as ischemia present or absent and acute or chronic or microangiopathy. Analysis used Fisher exact test and multivariate logistic regression. RESULTS: A total of 2028 patients were included; 814 had ischemic changes on CT. Subsequent stroke rate was 3.4% at 90 days and 1.5% at ≤2 days. Stroke risk was greater if baseline CT showed acute ischemia alone (10.6%; P=0.002), acute+chronic ischemia (17.4%; P=0.007), acute ischemia+microangiopathy (17.6%; P=0.019), or acute+chronic ischemia+microangiopathy (25.0%; P=0.029). Logistic regression found acute ischemia alone (odds ratio [OR], 2.61; 95% confidence interval [CI[, 1.22-5.57), acute+chronic ischemia (OR, 5.35; 95% CI, 1.71-16.70), acute ischemia+microangiopathy (OR, 4.90; 95% CI, 1.33-18.07), or acute+chronic ischemia+microangiopathy (OR, 8.04; 95% CI, 1.52-42.63) was associated with a greater risk at 90 days, whereas acute+chronic ischemia (OR, 10.78; 95% CI, 2.93-36.68), acute ischemia+microangiopathy (OR, 8.90; 95% CI, 1.90-41.60), and acute+chronic ischemia+microangiopathy (OR, 23.66; 95% CI, 4.34-129.03) had greater risk at ≤2 days. Only acute ischemia (OR, 2.70; 95% CI, 1.01-7.18; P=0.047) was associated with a greater risk at >2 days. CONCLUSIONS: In patients with transient ischemic attack/nondisabling stroke, CT evidence of acute ischemia alone or acute ischemia with chronic ischemia or microangiopathy was associated with increased subsequent stroke risk within 90 days.

Incidence, outcomes, and effect on quality of life of cranial nerve injury in the Carotid Revascularization Endarterectomy versus Stenting Trial.

OBJECTIVE: Cranial nerve injury (CNI) is the most common neurologic complication of carotid endarterectomy (CEA) and can cause significant chronic disability. Data from prior randomized trials are limited and provide no health-related quality of life (HRQOL) outcomes specific to CNI. Incidence of CNIs and their outcomes for patients in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) were examined to identify factors predictive of CNI and their impact on HRQOL. METHODS: Incidence of CNIs, baseline and procedural characteristics, outcomes, and HRQOL scores were evaluated in the 1151 patients randomized to CEA and undergoing surgery ≤30 days. Patients with CNI were identified and classified using case report forms, adverse event data, and clinical notes. Baseline and procedural characteristics were compared using descriptive statistics. Clinical outcomes at 1 and 12 months were analyzed. All data were adjudicated by two neurologists and a vascular surgeon. HRQOL was evaluated using the Medical Outcomes Short-Form 36 (SF-36) Health Survey to assess general health and Likert scales for disease-specific outcomes at 2 weeks, 4 weeks, and 12 months after CEA. The effect of CNI on SF-36 subscales was evaluated using random effects growth curve models, and Likert scale data were compared by ordinal logistic regression. RESULTS: CNI was identified in 53 patients (4.6%). Cranial nerves injured were VII (30.2%), XII (24.5%), and IX/X (41.5%), and 3.8% had Horner syndrome. CNI occurred in 52 of 1040 patients (5.0%) receiving general anesthesia and in one of 111 patients (0.9%) operated on under local anesthesia (P = .05). No other predictive baseline or procedural factors were identified. Deficits resolved in 18 patients (34%) at 1 month and in 42 of 52 patients (80.8%) by 1 year. One patient died before the 1-year follow-up visit. The HRQOL evaluation showed no statistical difference between groups with and without CNI at any interval. By Likert scale analysis, the group with CNI showed a significant difference in the difficulty eating/swallowing parameter at 2 and 4 weeks (P < .001) but not at 1 year. CONCLUSIONS: In CREST, CNI occurred in 4.6% of patients undergoing CEA, with 34% resolution at 30 days and 80.8% at 1 year. The incidence of CNI was significantly higher in patients undergoing general anesthesia. CNI had a small and transient effect on HRQOL, negatively affecting only difficulty eating/swallowing at 2 and 4 weeks but not at 1 year. On the basis of these findings, we conclude that CNI is not a trivial consequence of CEA but rarely results in significant long-term disability.

Characteristics of participants consenting versus declining follow-up for up to 10 years in a randomized clinical trial.

BACKGROUND: With patients living a decade or longer post-procedure, long-term data are needed to assess the durability of carotid artery stenting versus carotid endarterectomy. Identifying characteristics of those consenting or declining to continue in long-term follow-up may suggest strategies to improve retention in clinical trials. PURPOSE: This report describes differences between patients choosing or declining to continue follow-up for up to 10 years in the Carotid Revascularization Endarterectomy versus Stenting Trial. METHODS: Following completion of the primary outcome, patients who were in active Carotid Revascularization Endarterectomy versus Stenting Trial follow-up were asked to continue beyond their original 4-year commitment for a maximum of 10 years. The characteristics of those who consented were compared with those who declined. Univariate and multivariable logistic regression were used for analysis, and backwards stepwise logistic regression (the most parsimonious model) was used to determine the factors associated with continuation. RESULTS: Of the 1921 active Carotid Revascularization Endarterectomy versus Stenting Trial participants for whom consent to extend follow-up was requested, 1695 (88%; mean age: 68.4) consented; 226 (12%; mean age: 69.6) declined. Of those who did not consent versus those who consented, 66% versus 48% were symptomatic at baseline (p<0.0001), at follow-up 28% versus 20% were smokers (p=0.009), 85% versus 90% were hypertensive (p=0.01), and 84% versus 94% were dyslipidemic (p<0.0001). Additional factors that differed between those who did not consent and those who consented included the mean number of years in the study at time of consent (4.8 years vs 3.7 years (p=<0.0001)) and patients from sites that enrolled <30 patients compared to sites randomizing 30 or more (70% vs 52% (p<0.0001)). Multivariable logistic regression indicated that those with lesser odds of consenting to the extended follow-up were older (odds ratio: 0.80; 95% confidence interval: 0.67, 0.96), more likely to be symptomatic (odds ratio: 0.58; 95% confidence interval: 0.42, 0.80), smokers (odds ratio: 0.48; 95% confidence interval: 0.34, 0.70), were in the study 5+ years versus <3 (odds ratio: 0.21; 95% confidence interval: 0.13, 0.34), and at a site that randomized <30 patients (odds ratio: 0.46; 95% confidence interval: 0.33, 0.63), while patients with dyslipidemia at follow-up had increased odds of consenting (odds ratio: 2.28 (1.47, 3.54)). CONCLUSION: Symptomatic status, increasing age, randomized at lower volume centers, and longer time in follow-up were associated with reduced odds of consenting to long-term follow-up. Identifying factors associated with reduced willingness to extend participation long-term can suggest targeted strategies to improve retention in future clinical trials.

A prospective cohort study of patients with transient ischemic attack to identify high-risk clinical characteristics.

BACKGROUND AND PURPOSE: The occurrence of a transient ischemic attack (TIA) increases an individual's risk for subsequent stroke. The objectives of this study were to determine clinical features of patients with TIA associated with impending (≤7 days) stroke and to develop a clinical prediction score for impending stroke. METHODS: We conducted a prospective cohort study at 8 Canadian emergency departments for 5 years. We enrolled patients with a new TIA. Our outcome was subsequent stroke within 7 days of TIA diagnosis. RESULTS: We prospectively enrolled 3906 patients, of which 86 (2.2%) experienced a stroke within 7 days. Clinical features strongly correlated with having an impending stroke included first-ever TIA, language disturbance, longer duration, weakness, gait disturbance, elevated blood pressure, atrial fibrillation on ECG, infarction on computed tomography, and elevated blood glucose. Variables less associated with having an impending stroke included vertigo, lightheadedness, and visual loss. From this cohort, we derived the Canadian TIA Score which identifies the risk of subsequent stroke≤7 days and consists of 13 variables. This model has good discrimination with a c-statistic of 0.77 (95% confidence interval, 0.73-0.82). CONCLUSIONS: Patients with TIA with their first TIA, language disturbance, duration of symptoms≥10 minutes, gait disturbance, atrial fibrillation, infarction on computed tomography, elevated platelets or glucose, unilateral weakness, history of carotid stenosis, and elevated diastolic blood pressure are at higher risk for an impending stroke. Patients with vertigo and no high-risk features are at low risk. The Canadian TIA Score quantifies the impending stroke risk following TIA.

Derivation of a clinical prediction score for the diagnosis of clinically significant symptomatic carotid artery disease.

OBJECTIVES: Emergent vascular imaging identifies a subset of patients requiring immediate specialized care (i.e. carotid stenosis > 50%, dissection or free-floating thrombus). However, most TIA patients do not have these findings, so it is inefficient to image all TIA patients in crowded emergency departments (ED). Our objectives were to derive and internally validate a clinical prediction score for clinically significant carotid artery disease in TIA patients. METHODS: This was a planned secondary analysis of a prospective cohort study from 14 Canadian EDs. Among 11555 consecutive adult ED patients with TIA/minor stroke symptoms over 12 years, 9882 had vascular imaging and were included in the analysis. Our main outcome was clinically significant carotid artery disease, defined as extracranial internal carotid stenosis ≥ 50%, dissection, or thrombus in the internal carotid artery, with contralateral symptoms. RESULTS: Of 9882 patients, 888 (9.0%) had clinically significant carotid artery disease. Logistic regression was used to derive a 13-variable reduced model. We simplified the model into a score (Symcard [Symptomatic carotid artery disease] Score), with suggested cut-points for high, medium, and low-risk stratification. A substantial portion (38%) of patients were classified as low-risk, 33.8% as medium risk, and 28.2% as high risk. At the low-risk cut-point, sensitivity was 92.9%, specificity 41.1%, and diagnostic yield 1.7%. CONCLUSIONS: This simple score can predict carotid artery disease in TIA patients using readily available information. It identifies low-risk patients who can defer vascular imaging to an outpatient or specialty clinic setting. Medium-risk patients may undergo imaging immediately or with slight delay, depending on local resources. High-risk patients should undergo urgent vascular imaging.

RéSUMé: OBJECTIFS: L'imagerie vasculaire émergente permet d'identifier un sous-ensemble de patients nécessitant des soins spécialisés immédiats (c.-à-d. sténose carotidienne >50 %, dissection ou thrombus flottant). Cependant, la plupart des patients atteints de RTI ne présentent pas ces résultats, il est donc inefficace d'effectuer une imagerie de tous les patients atteints de RTI dans les services d'urgence (ER) surpeuplés. Nos objectifs étaient de calculer et de valider en interne un score de prédiction clinique pour la maladie carotide cliniquement significative chez les patients atteints d'une AIT MéTHODES: Il s'agissait d'une analyse secondaire planifiée d'une étude de cohorte prospective menée auprès de 14 DE canadiens. Parmi les 11555 patients adultes consécutifs atteints d'un EI présentant des symptômes d'AIT/AVC mineur au cours des 12 dernières années, 9882 ont reçu une imagerie vasculaire et ont été inclus dans l'analyse. Notre principal critère de jugement était la maladie carotide cliniquement significative, définie comme une sténose extracrânienne de la carotide interne à 50 %, une dissection ou un thrombus dans l'artère carotide interne, avec des symptômes contralatéraux. RéSULTATS: Sur 9882 patients, 888 (9,0 %) présentaient une maladie de l'artère carotide cliniquement significative. La régression logistique a été utilisée pour obtenir un modèle réduit à 13 variables. Nous avons simplifié le modèle en un score (Symcard [Symptomatic carotid artery disease] Score), avec des points de coupure suggérés pour la stratification à risque élevé, moyen et faible. Une proportion importante (38,0 %) des patients ont été classés à faible risque, 33,8 % à risque moyen et 28,2 % à risque élevé. Au seuil de faible risque, la sensibilité était de 92,9 %, la spécificité de 41,1 % et le rendement diagnostique de 1,7 %. CONCLUSIONS: Ce score simple permet de prédire la maladie de l'artère carotide chez les patients atteints d'AIT en utilisant des informations facilement disponibles. Il identifie les patients à faible risque qui peuvent reporter l'imagerie vasculaire à un établissement de consultation externe ou de spécialité. Les patients à risque moyen peuvent subir une imagerie immédiatement ou avec un léger délai, selon les ressources locales. Les patients à haut risque doivent subir une imagerie vasculaire urgente.

A Multicentre Prospective Cohort Study to Identify High-Risk Transient Ischemic Attack/Minor Stroke Patients Benefitting from Echocardiography.

BACKGROUND: We aimed to derive a clinical decision rule to identify patients with transient ischemic attack (TIA) or minor stroke most likely to benefit from echocardiography. METHODS: This multicentre prospective cohort study enrolled adults diagnosed with TIA/minor stroke in the emergency department who underwent echocardiograms within 90 days, from 13 Canadian academic emergency departments from October 2006 to May 2017. Our outcome was clinically significant echocardiogram findings. RESULTS: In 7149 eligible patients, a clinically significant finding was found in 556 (7.8%). There were a further 2421 (33.9%) with potentially significant findings. History of heart failure (adjusted odds ratio [OR], 3.9) or coronary artery disease (OR, 2.7) were the factors most strongly associated with clinically significant echocardiogram findings, whereas young age, male sex, valvular heart disease, and infarct (any age) on neuroimaging were modestly associated (OR, 1.3-1.9). The model combining these predictors into a score (range: 0-15), had a C-statistic of 0.67 (95% confidence interval [CI], 0.65-0.70). A cut point of 6 points or more classified 6.6% of cases as high likelihood, defined as > 15% for clinically significant echocardiogram findings. CONCLUSIONS: Echocardiography is a very useful test in the investigations of patients with TIA/minor stroke. We identified high-risk clinical features-combined to create a clinical decision rule-to identify which patients with TIA/minor stroke are likely to have clinically significant echocardiogram findings requiring an immediate change in management. These patients should have echocardiography prioritized, whereas others may continue to have echocardiography conducted in a less urgent fashion.

Stroke after carotid stenting and endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).

BACKGROUND: Stroke occurs more commonly after carotid artery stenting than after carotid endarterectomy. Details regarding stroke type, severity, and characteristics have not been reported previously. We describe the strokes that have occurred in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). METHODS AND RESULTS: CREST is a randomized, open-allocation, controlled trial with blinded end-point adjudication. Stroke was a component of the primary composite outcome. Patients who received their assigned treatment within 30 days of randomization were included. Stroke was adjudicated by a panel of board-certified vascular neurologists with secondary central review of clinically obtained brain images. Stroke type, laterality, timing, and outcome were reported. A periprocedural stroke occurred among 81 of the 2502 patients randomized and among 69 of the 2272 in the present analysis. Strokes were predominantly minor (81%, n=56), ischemic (90%, n=62), in the anterior circulation (94%, n=65), and ipsilateral to the treated artery (88%, n=61). There were 7 hemorrhages, which occurred 3 to 21 days after the procedure, and 5 were fatal. Major stroke occurred in 13 (0.6%) of the 2272 patients. The estimated 4-year mortality after stroke was 21.1% compared with 11.6% for those without stroke. The adjusted risk of death at 4 years was higher after periprocedural stroke (hazard ratio, 2.78; 95% confidence interval, 1.63-4.76). CONCLUSIONS: Stroke, particularly severe stroke, was uncommon after carotid intervention in CREST, but stroke was associated with significant morbidity and was independently associated with a nearly 3-fold increased future mortality. The delayed timing of major and hemorrhagic stroke after revascularization suggests that these strokes may be preventable.

Stenting versus endarterectomy for treatment of carotid-artery stenosis.

BACKGROUND: Carotid-artery stenting and carotid endarterectomy are both options for treating carotid-artery stenosis, an important cause of stroke. METHODS: We randomly assigned patients with symptomatic or asymptomatic carotid stenosis to undergo carotid-artery stenting or carotid endarterectomy. The primary composite end point was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke within 4 years after randomization. RESULTS: For 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P=0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P=0.84) or sex (P=0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P=0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P=0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P=0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P=0.18), for stroke (4.1% vs. 2.3%, P=0.01), and for myocardial infarction (1.1% vs. 2.3%, P=0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P=0.85). CONCLUSIONS: Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy. (ClinicalTrials.gov number, NCT00004732.)

Ninety-Day Stroke or Transient Ischemic Attack Recurrence in Patients Prescribed Anticoagulation in the Emergency Department With Atrial Fibrillation and a New Transient Ischemic Attack or Minor Stroke.

Background For patients with atrial fibrillation seen in the emergency department (ED) following a transient ischemic attack (TIA) or minor stroke, the impact of initiating oral anticoagulation immediately rather than deferring the decision to outpatient follow-up is unknown. Methods and Results We conducted a planned secondary data analysis of a prospective cohort of 11 507 adults in 13 Canadian EDs between 2006 and 2018. Patients were eligible if they were aged 18 years or older, with a final diagnosis of TIA or minor stroke with previously documented or newly diagnosed atrial fibrillation. The primary outcome was subsequent stroke, recurrent TIA, or all-cause mortality within 90 days of the index TIA diagnosis. Secondary outcomes included stroke, recurrent TIA, or death and rates of major bleeding. Of 11 507 subjects with TIA/minor stroke, atrial fibrillation was identified in 11.2% (1286, mean age, 77.3 [SD 11.1] years, 52.4% male). Over half (699; 54.4%) were already taking anticoagulation, 89 (6.9%) were newly prescribed anticoagulation in the ED. By 90 days, 4.0% of the atrial fibrillation cohort had experienced a subsequent stroke, 6.5% subsequent TIA, and 2.6% died. Results of a multivariable logistic regression indicate no association between prescribed anticoagulation in the ED and these 90-day outcomes (composite odds ratio, 1.37 [95% CI, 0.74-2.52]). Major bleeding was found in 5 patients, none of whom were in the ED-initiated anticoagulation group. Conclusions Initiating oral anticoagulation in the ED following new TIA was not associated with lower recurrence rates of neurovascular events or all-cause mortality in patients with atrial fibrillation.

Impact of disability status on ischemic stroke costs in Canada in the first year.

BACKGROUND: Longitudinal, patient-level data on resource use and costs after an ischemic stroke are lacking in Canada. The objectives of this analysis were to calculate costs for the first year post-stroke and determine the impact of disability on costs. METHODOLOGY: The Economic Burden of Ischemic Stroke (BURST) Study was a one-year prospective study with a cohort of ischemic stroke patients recruited at 12 Canadian stroke centres. Clinical history, disability, health preference and resource utilization information was collected at discharge, three months, six months and one year. Resources included direct medical costs (2009 CAN$) such as emergency services, hospitalizations, rehabilitation, physician services, diagnostics, medications, allied health professional services, homecare, medical/assistive devices, changes to residence and paid caregivers, as well as indirect costs. Results were stratified by disability measured at discharge using the modified Rankin Score (mRS): non-disabling stroke (mRS 0-2) and disabling stroke (mRS 3-5). RESULTS: We enrolled 232 ischemic stroke patients (age 69.4 ± 15.4 years; 51.3% male) and 113 (48.7%) were disabled at hospital discharge. The average annual cost was $74,353; $107,883 for disabling strokes and $48,339 for non-disabling strokes. CONCLUSIONS: An average annual cost for ischemic stroke was calculated in which a disabling stroke was associated with a two-fold increase in costs compared to NDS. Costs during the hospitalization to three months phase were the highest contributor to the annual cost. A "back of the envelope" calculation using 38,000 stroke admissions and the average annual cost yields $2.8 billion as the burden of ischemic stroke.

Risk of stroke is low after transient ischemic attack presentation with isolated dizziness.

OBJECTIVE: Stroke presenting as dizziness is a diagnostic challenge in frontline settings, given the multitude of benign conditions that present similarly. The risk of stroke after episodic dizziness is unknown, leading to divergent guidance on optimal workup and management. Prior TIA risk scores have shown a history of dizziness is a negative predictor of subsequent stroke. Our objective was to assess the subsequent stroke risk within 90 days following emergency department assessment (ED) for isolated dizziness diagnosed as TIA during the index visit. METHODS: We conducted prospective, multicenter cohort studies at 13 Canadian EDs over 11 years. We enrolled patients diagnosed with TIA and compared patients with isolated dizziness to those with other neurological deficits. Our primary outcome was subsequent stroke within 90 days. Secondary outcomes were subsequent stroke within 2, 7, and 30 days, respectively, as well as subsequent TIA within 90 days. RESULTS: Only 4/483 (0.8%) patients with isolated dizziness had a stroke within 90 days compared to 320/11024 (2.9%) of those with any focal neurological sign or symptom (RR 0.29, 95% CI 0.11-0.76). Over the first 90 days, the two groups differ significantly in their probability of stroke (p = 0.007). Subsequent TIA was also significantly less common in the isolated dizziness group (1.7% vs. 5.6%, p = 0.001) with a relative risk of 0.30 (95% CI 0.15-0.60). CONCLUSION: The risk of subsequent stroke following ED presentation for TIA is low when the presenting symptoms are isolated dizziness.

RéSUMé: OBJECTIF: Les accidents vasculaires cérébraux (AVC) se présentant sous forme de vertiges constituent un défi diagnostique en première ligne, étant donné la multitude d'affections bénignes qui se présentent de la même manière. Le risque d'accident vasculaire cérébral (AVC) après des vertiges épisodiques est inconnu, ce qui donne lieu à des conseils divergents sur le bilan et la prise en charge optimaux. Des scores de risque d'AIT antérieurs ont montré que des antécédents de vertiges sont un facteur prédictif négatif d'accident vasculaire cérébral ultérieur. Notre objectif était d'évaluer le risque ultérieur d'accident vasculaire cérébral (AVC) dans les 90 jours suivant l'évaluation aux urgences d'un étourdissement isolé diagnostiqué comme un AIT lors de la visite de référence. MéTHODES: Nous avons mené des études de cohorte prospectives multicentriques dans 13 services d'urgence canadiens pendant 11 ans. Nous avons recruté des patients ayant reçu un diagnostic d'AIT et avons comparé les patients présentant des vertiges isolés à ceux présentant d'autres déficits neurologiques. Nous avons inscrit des patients ayant reçu un diagnostic d'AIT et comparé des patients ayant des étourdissements isolés à ceux présentant d'autres déficits neurologiques. Notre résultat primaire était l'AVC subséquent dans les 90 jours. Les résultats secondaires étaient l'AVC subséquent dans les 2, 7 et 30 jours, respectivement, ainsi que l'AIT subséquent dans les 90 jours. RéSULTATS: Seuls 4/483 (0,8 %) des patients présentant des vertiges isolés ont eu un AVC dans les 90 jours, contre 320/11 024 (2,9 %) de ceux présentant un signe ou symptôme neurologique focal (RR 0,29, IC 95 % 0,11-0,76). Au cours des 90 premiers jours, les deux groupes diffèrent significativement en termes de probabilité d'AVC (p = 0,007). L'AIT ultérieur était également significativement moins fréquent dans le groupe des vertiges isolés (1,7 % contre 5,6 %, p = 0,001) avec un risque relatif de 0,30 (IC 95 % 0,15-0,60). CONCLUSIONS: Le risque d'AVC ultérieur après une présentation aux urgences pour un AIT est faible lorsque les symptômes présentés sont des étourdissements isolés.

Safety of stenting and endarterectomy by symptomatic status in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

BACKGROUND AND PURPOSE: The safety of carotid artery stenting (CAS) and carotid endarterectomy (CEA) has varied by symptomatic status in previous trials. The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) data were analyzed to determine safety in symptomatic and asymptomatic patients. METHODS: CREST is a randomized trial comparing safety and efficacy of CAS versus CEA in patients with high-grade carotid stenoses. Patients were defined as symptomatic if they had relevant symptoms within 180 days of randomization. The primary end point was stroke, myocardial infarction, or death within the periprocedural period or ipsilateral stroke up to 4 years. RESULTS: For 1321 symptomatic and 1181 asymptomatic patients, the periprocedural aggregate of stroke, myocardial infarction, and death did not differ between CAS and CEA (5.2% versus 4.5%; hazard ratio, 1.18; 95% CI, 0.82 to 1.68; P=0.38). The stroke and death rate was higher for CAS versus CEA (4.4% versus 2.3%; hazard ratio, 1.90; 95% CI, 1.21 to 2.98; P=0.005). For symptomatic patients, the periprocedural stroke and death rates were 6.0%±0.9% for CAS and 3.2%±0.7% for CEA (hazard ratio, 1.89; 95% CI, 1.11 to 3.21; P=0.02). For asymptomatic patients, the stroke and death rates were 2.5%±0.6% for CAS and 1.4%±0.5% for CEA (hazard ratio, 1.88; 95% CI, 0.79 to 4.42; P=0.15). Rates were lower for those aged <80 years. CONCLUSIONS: There were no significant differences between CAS versus CEA by symptomatic status for the primary CREST end point. Periprocedural stroke and death rates were significantly lower for CEA in symptomatic patients. However, for both CAS and CEA, stroke and death rates were below or comparable to those of previous randomized trials and were within the complication thresholds suggested in current guidelines for both symptomatic and asymptomatic patients.

Prospective validation of the ABCD2 score for patients in the emergency department with transient ischemic attack.

BACKGROUND: The ABCD2 score (Age, Blood pressure, Clinical features, Duration of symptoms and Diabetes) is used to identify patients having a transient ischemic attack who are at high risk for imminent stroke. However, despite its widespread implementation, the ABCD2 score has not yet been prospectively validated. We assessed the accuracy of the ABCD2 score for predicting stroke at 7 (primary outcome) and 90 days. METHODS: This prospective cohort study enrolled adults from eight Canadian emergency departments who had received a diagnosis of transient ischemic attack. Physicians completed data forms with the ABCD2 score before disposition. The outcome criterion, stroke, was established by a treating neurologist or by an Adjudication Committee. We calculated the sensitivity and specificity for predicting stroke 7 and 90 days after visiting the emergency department using the original "high-risk" cutpoint of an ABCD2 score of more than 5, and the American Heart Association recommendation of a score of more than 2. RESULTS: We enrolled 2056 patients (mean age 68.0 yr, 1046 (50.9%) women) who had a rate of stroke of 1.8% at 7 days and 3.2% at 90 days. An ABCD2 score of more than 5 had a sensitivity of 31.6% (95% confidence interval [CI] 19.1-47.5) for stroke at 7 days and 29.2% (95% CI 19.6-41.2) for stroke at 90 days. An ABCD2 score of more than 2 resulted in sensitivity of 94.7% (95% CI 82.7-98.5) for stroke at 7 days with a specificity of 12.5% (95% CI 11.2-14.1). The accuracy of the ABCD2 score as calculated by either the enrolling physician (area under the curve 0.56; 95% CI 0.47-0.65) or the coordinating centre (area under the curve 0.65; 95% CI 0.57-0.73) was poor. INTERPRETATION: This multicentre prospective study involving patients in emergency departments with transient ischemic attack found the ABCD2 score to be inaccurate, at any cut-point, as a predictor of imminent stroke. Furthermore, the ABCD2 score of more than 2 that is recommended by the American Heart Association is nonspecific.

Predictors of neurologists confirming or overturning emergency physicians' diagnosis of TIA or stroke.

BACKGROUND: Transient ischemic attack (TIA) and non-disabling stroke are common emergency department (ED) presentations. Currently, there are no prospective multicenter studies determining predictors of neurologists confirming a diagnosis of cerebral ischemia in patients discharged with a diagnosis of TIA or stroke. The objectives were to (1) calculate the concordance between emergency physicians and neurologists for the outcome of diagnosing TIA or stroke, and (2) identify characteristics associated with neurologists diagnosing a stroke mimic. METHODS: This was a planned sub-study of a prospective cohort study at 14 Canadian EDs enrolling patients diagnosed with TIA or non-disabling stroke from 2006 to 2017. Logistic regression was used to identify factors associated with neurologists' diagnosis of cerebral ischemia. Our primary outcome was the composite outcome of cerebral ischemia (TIA or non-disabling stroke) based on the neurologists' assessment. RESULTS: The diagnosis of cerebral ischemia was confirmed by neurologists in 5794 patients (55.4%). The most common identified stroke mimics were migraine (18%), peripheral vertigo (7%), syncope (4%), and seizure (3%). Over a third of patients (38.4%) ultimately had an undetermined aetiology for their symptoms. The strongest predictors of cerebral ischemia confirmation were infarct on CT (OR 1.83, 95% CI 1.65-2.02), advanced age (OR comparing 75th-25th percentiles 1.67, 1.55-1.80), language disturbance (OR 1.92, 1.75-2.10), and smoking (OR 1.67, 1.46-1.91). The strongest predictors of stroke mimics were syncope (OR 0.59, 0.48-0.72), vertigo (OR 0.52, 0.45-0.59), bilateral symptoms (OR 0.60, 0.50-0.72), and confusion (OR 0.50, 0.44-0.57). CONCLUSION: Physicians should have a high index of suspicion of cerebral ischemia in patients with advanced age, smoking history, language disturbance, or infarcts on CT. Physicians should discriminate in which patients to pursue stroke investigations on when deemed at minimal risk of cerebral ischemia, including those with isolated vertigo, syncope, or bilateral symptoms.

RéSUMé: CONTEXTE: L'accident ischémique transitoire (AIT) et l'accident vasculaire cérébral (AVC) non invalidant sont des présentations courantes dans les services d'urgence. Actuellement, il n'existe pas d'études prospectives multicentriques déterminant les facteurs prédictifs de la confirmation par les neurologues d'un diagnostic d'ischémie cérébrale chez les patients sortis de l'hôpital avec un diagnostic d'AIT ou d'AVC. Les objectifs étaient de (1) calculer la concordance entre les urgentistes et les neurologues pour le résultat du diagnostic de l'AIT ou de l'AVC, et (2) identifier les caractéristiques associées au diagnostic par les neurologues d'une imitation d'AVC. MéTHODES: Il s'agissait d'une sous-étude planifiée d'une étude de cohorte prospective dans 14 services d'urgence canadiens recrutant des patients diagnostiqués avec un AIT ou un AVC non invalidant de 2006 à 2017. Une régression logistique a été utilisée pour identifier les facteurs associés au diagnostic d'ischémie cérébrale par les neurologues. Notre résultat principal était le résultat composite de l'ischémie cérébrale (AIT ou accident vasculaire cérébral non invalidant) selon l'évaluation des neurologues. RéSULTATS: Le diagnostic d'ischémie cérébrale a été confirmé par des neurologues chez 5 794 patients (55,4 %). Les imitateurs d'AVC identifiés les plus courants étaient la migraine (18 %), le vertige périphérique (7 %), la syncope (4 %) et les convulsions (3 %). Plus d'un tiers des patients (38,4 %) avaient finalement une étiologie indéterminée pour leurs symptômes. Les prédicteurs les plus forts de la confirmation de l'ischémie cérébrale étaient l'infarctus au scanner (OR 1.83, IC 95 % 1.65­2.02), l'âge avancé (OR comparant les 75e et 25e percentiles 1.67, 1.55­1.80), les troubles du langage (OR 1.92, 1.75­2.10) et le tabagisme (OR 1.67, 1.46­1.91). Les prédicteurs les plus forts d'imitateurs d'AVC étaient la syncope (OR 0.59, 0.48­0.72), le vertige (OR 0.52, 0.45­0.59), les symptômes bilatéraux (OR 0.60, 0.50­0.72) et la confusion (OR 0.50, 0.44­0.57). CONCLUSION: Les médecins devraient avoir un indice élevé de suspicion d'ischémie cérébrale chez les patients ayant un âge avancé, des antécédents de tabagisme, des troubles du langage ou des infarctus au scanner. Les médecins doivent distinguer les patients sur lesquels poursuivre des investigations sur un AVC lorsqu'ils sont jugés à risque minimal d'ischémie cérébrale, y compris ceux présentant des vertiges isolés, une syncope ou des symptômes bilatéraux.

Prospective validation of Canadian TIA Score and comparison with ABCD2 and ABCD2i for subsequent stroke risk after transient ischaemic attack: multicentre prospective cohort study.

OBJECTIVE: To validate the previously derived Canadian TIA Score to stratify subsequent stroke risk in a new cohort of emergency department patients with transient ischaemic attack. DESIGN: Prospective cohort study. SETTING: 13 Canadian emergency departments over five years. PARTICIPANTS: 7607 consecutively enrolled adult patients attending the emergency department with transient ischaemic attack or minor stroke. MAIN OUTCOME MEASURES: The primary outcome was subsequent stroke or carotid endarterectomy/carotid artery stenting within seven days. The secondary outcome was subsequent stroke within seven days (with or without carotid endarterectomy/carotid artery stenting). Telephone follow-up used the validated Questionnaire for Verifying Stroke Free Status at seven and 90 days. All outcomes were adjudicated by panels of three stroke experts, blinded to the index emergency department visit. RESULTS: Of the 7607 patients, 108 (1.4%) had a subsequent stroke within seven days, 83 (1.1%) had carotid endarterectomy/carotid artery stenting within seven days, and nine had both. The Canadian TIA Score stratified the risk of stroke, carotid endarterectomy/carotid artery stenting, or both within seven days as low (risk ≤0.5%; interval likelihood ratio 0.20, 95% confidence interval 0.09 to 0.44), medium (risk 2.3%; interval likelihood ratio 0.94, 0.85 to 1.04), and high (risk 5.9% interval likelihood ratio 2.56, 2.02 to 3.25) more accurately (area under the curve 0.70, 95% confidence interval 0.66 to 0.73) than did the ABCD2 (0.60, 0.55 to 0.64) or ABCD2i (0.64, 0.59 to 0.68). Results were similar for subsequent stroke regardless of carotid endarterectomy/carotid artery stenting within seven days. CONCLUSION: The Canadian TIA Score stratifies patients' seven day risk for stroke, with or without carotid endarterectomy/carotid artery stenting, and is now ready for clinical use. Incorporating this validated risk estimate into management plans should improve early decision making at the index emergency visit regarding benefits of hospital admission, timing of investigations, and prioritisation of specialist referral.