Summary Background In the randomised Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the primary endpoint did not differ between carotid artery stenting and carotid ...endarterectomy in patients with symptomatic and asymptomatic stenosis. A prespecified secondary aim was to examine differences by sex. Methods Patients who were asymptomatic or had had a stroke or transient ischaemic attack within 180 days before random allocation were enrolled in CREST at 117 clinical centres in the USA and Canada. The primary outcome was the composite of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke within 4 years. We used standard survival methods including Kaplan-Meier survival curves and sex-by-treatment interaction term to assess the relation between patient factors and risk of reaching the primary outcome. Analyses were by intention to treat. CREST is registered with ClinicalTrials.gov , NCT00004732. Findings Between Dec 21, 2000, and July 18, 2008, 2502 patients were randomly assigned to carotid endarterectomy (n=1240) or carotid artery stenting (n=1262), 872 (34·9%) of whom were women. Rates of the primary endpoint for carotid artery stenting compared with carotid endarterectomy were 6·2% versus 6·8% in men (hazard ratio HR 0·99, 95% CI 0·66–1·46) and 8·9% versus 6·7% in women (1·35, 0·82–2·23). There was no significant interaction in the primary endpoint between sexes (interaction p=0·34). Periprocedural events occurred in 35 (4·3%) of 807 men assigned to carotid artery stenting compared with 40 (4·9%) of 823 assigned to carotid endarterectomy (HR 0·90, 95% CI 0·57–1·41) and 31 (6·8%) of 455 women assigned to carotid artery stenting compared with 16 (3·8%) of 417 assigned to carotid endarterectomy (1·84, 1·01–3·37; interaction p=0·064). Interpretation Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy whereas there is little difference in men. Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women. Funding National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions (formerly Guidant).
In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, ...myocardial infarction, or death (7.2% and 6.8%, respectively; P=0.51). Stroke was more common with carotid-artery stenting than carotid endarterectomy; myocardial infarction was more common with carotid endarterectomy. The 4-year rate of stroke or death was 6.4% for carotid-artery stenting and 4.7% for carotid endarterectomy (P=0.03).
In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, myocardial infarction, or death (7.2% and 6.8%, respectively).
Carotid-artery atherosclerosis is an important cause of ischemic stroke.
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Carotid endarterectomy has been established as effective treatment for both symptomatic patients and asymptomatic patients.
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Carotid-artery stenting is another option for treatment. The results of randomized trials comparing carotid-artery stenting and carotid endarterectomy for use in symptomatic patients are conflicting.
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The primary aim of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) was to compare the outcomes of carotid-artery stenting with those of carotid endarterectomy among patients with symptomatic or asymptomatic extracranial carotid stenosis.
Methods
Study Design
CREST is a randomized, controlled trial with blinded end-point adjudication. Ethics review . . .
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.
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.
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.
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.
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).
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).
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.
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.
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.
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).
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.
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.
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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.
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).
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.
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.
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.
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.
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).
The risk of subsequent stroke following ED presentation for TIA is low when the presenting symptoms are isolated dizziness.
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.
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.
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).
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.
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.
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