Ariane Mackey

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.)

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 sex on outcomes of stenting versus endarterectomy: a subgroup analysis of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)

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).

The output organization of the substantia nigra in primate as revealed by a retrograde double labeling method

The cellular origin and degree of collateralization of the efferent projections of the substantia nigra pars reticulata (SNr) in the squirrel monkey (Saimiri sciureus) were studied using the following combinations of fluorescent retrograde tracers: Evans blue and DAPI-Primuline, Fast blue and Nuclear yellow, True blue and Nuclear yellow. In a first series of experiments one tracer was injected in the ventral anterior (VA) and ventral lateral (VL) thalamic nuclei, and the complementary tracer was delivered in the peribrachial area of midbrain tegmentum. After thalamo-tegmental injections numerous nigrothalamic neurons occur in clusters, particularly in rostrolateral part of SNr, whereas the nigrotegmental neurons prevail in caudomedial segment of SNr. However, a significant overlap exists between these two populations. The nigrothalamic and nigrotegmental neurons are present in about equal number in SNr with as much as 60% of these neurons being double-labeled. In a second series of experiments injections were made concomitantly in VA/VL nuclei and in superior colliculus. After thalamo-collicular injections the nigrothalamic neurons are found in larger number than the nigrocollicular neurons which are mostly confined to the middle third of SNr. About 15-20% of all SNr positive neurons are double-labeled, although this proportion climbs to 30-40% in certain sections taken through the middle third of SNr. Finally, injections were made concomittantly in superior colliculus and in midbrain tegmentum. In contrast to the findings obtained after thalamo-tegmental and thalamo-collicular injections, only about 10% of SNr neurons appear to be double-labeled after colliculo-tegmental injections. All injections made in present study have produced retrograde cell labeling in contralateral SNr. However, by far the largest number of contralateral labeled neurons is found after superior colliculus injection. These findings reveal that the SNr neurons in primate, as those in rat and cat, display a high degree of axonal branching. As such, the output organization of SNr appears to differ markedly from that of the substantia nigra pars compacta, but is remarkably similar to that of the internal pallidum which is the other major output structure of the basal ganglia.

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.

Does Sex Matter? Thirty-Day Stroke and Death Rates After Carotid Artery Stenting in Women Versus Men: Results From the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) Lead-in Phase

Background and Purpose— Several carotid endarterectomy randomized, controlled trials and series have reported higher perioperative stroke and death rates for women compared with men. The potential for this same relationship with carotid artery stenting was examined in the lead-in phase of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Methods— CREST compares efficacy of carotid endarterectomy and carotid artery stenting in preventing stroke, myocardial infarction, and death in the periprocedural period and ipsilateral stroke over the follow-up period. CREST included a “lead-in” phase of symptomatic (≥50% stenosis) and asymptomatic (≥70% stenosis) patients. Patients were examined by a neurologist preprocedure, at 24 hours, and at 30 days. Review of stroke and death was by an independent events committee. The association of sex with periprocedural stroke and death was examined in 1564 patients undergoing carotid artery stenting (26.5% symptomatic). Results— Women comprised 37% of the lead-in cohort and did not differ from men by age, symptomatic status, or characteristics of the internal carotid artery. The 30-day stroke and death rate for women was 4.5% (26 of 579; 95% CI, 3.0% to 6.5%) compared with 4.2% (41 of 985; 95% CI, 3.0% to 5.6%) for men. The difference in stroke and death rate was not significant nor were there any significant differences by sex after adjustment for age, arterial characteristics, or cardiovascular risk factors. Conclusions— These results do not provide evidence that women have a higher carotid artery stenting stroke and death rate compared with men. The potential differential periprocedural risk by sex will be prospectively addressed in the randomized phase of CREST.

Atherosclerotic Burden Findings in Young Cryptogenic Stroke Patients With and Without a Patent Foramen Ovale

Background and Purpose— To further determine the mechanisms of cryptogenic stroke or transient ischemic attack in young patients, we evaluated indices of atherosclerosis in patients ≤55 years old diagnosed with cryptogenic cerebrovascular event comparing those with patent foramen ovale (PFO) with those without PFO. Methods— This was a prospective study including 100 consecutive patients ≤55 years old (mean age, 45±8 years; 56 males) diagnosed with cryptogenic stroke/transient ischemic attack. PFO was identified in 59 of these patients with the use of transesophageal echocardiography with contrast study. The following surrogate markers of atherosclerosis were evaluated in all patients: carotid intima media thickness as measured by carotid ultrasonography and endothelial function as determined by brachial flow-mediated vasodilation. The same measurements were obtained in a control group of 50 age- and sex-matched control subjects. Results— Patients without PFO were more likely to be current smokers and obese and more frequently had a history of hypertension and dyslipidemia. Carotid intima media thickness measurements were higher (P<0.0001) in patients without PFO (1.03±0.31 mm) compared with those with PFO (0.75±0.20 mm) and control subjects (0.79±0.17 mm). The absence of PFO was also associated with lower brachial flow-mediated vasodilation (without PFO: 5.04±3.39%; with PFO: 7.16±4.09%; control subjects: 7.33±4.07%; P=0.02). There were no differences in carotid intima media thickness and flow-mediated vasodilation between patients with stroke/transient ischemic attack with PFO and control subjects. The presence of PFO was independently associated with reduced carotid intima media thickness (P<0.0001) and increased flow-mediated vasodilation (P=0.019). Conclusions— In patients ≤55 years old diagnosed with cryptogenic stroke/transient ischemic attack, the presence of PFO was associated with a lower atherosclerotic burden as measured by carotid intima media thickness and endothelial function with no differences compared with a control group without cerebrovascular event. These results suggest that an atherosclerotic-mediated mechanism may be involved in cryptogenic stroke/transient ischemic attack in patients without PFO, whereas a nonatherosclerotic mechanism may mediate the cerebrovascular event in the presence of PFO.

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.

Incidence, Timing, and Predictive Factors of New-Onset Migraine Headache Attack After Transcatheter Closure of Atrial Septal Defect or Patent Foramen Ovale

The objectives of this study were to evaluate the incidence, predictive factors, and duration of migraine headache attack (MHA) after transcatheter atrial septal defect (ASD) or patent foramen ovale (PFO) closure. A total of 260 consecutive patients who underwent ASD or PFO closure in our center answered a structured headache questionnaire focused in 3 period times, including (1) at baseline (just before closure), (2) within the 3 months after ASD-PFO closure, and (3) at the last (median 27 months, range 6 to 80 months) follow-up. All questionnaires were evaluated by a neurologist who established the diagnosis of MHA with or without aura, according to International Headache Society criteria. The Amplatzer ASD or PFO device was used in 95% of the patients, and aspirin, for at least 6 months, was the antithrombotic treatment in 91% of the cases. A total of 185 patients (71%) had no history of MHA before ASD-PFO closure, and these constituted the study population (mean age 39 +/- 21 years). MHA occurred in 13 patients (7%) after ASD-PFO closure, with aura in 9 of them. MHA appeared after a median of 10 days (range 0.3 to 30 days) after the procedure and were still present at the last follow-up (23 +/- 17 months) in 9 patients (69%). The median number of MHA within the 3 months after the procedure was 4 per month (interquartile range 1 to 23), and decreased to 1 per month (interquartile range 0.3 to 1) at the latest follow-up (p = 0.03). Compared with the patients who did not develop MHA, patients with MHA after ASD-PFO closure were younger (26 +/- 16 vs 39 +/- 21 years; p = 0.02) and were more likely to have undergone ASD closure (100% vs 58%; p = 0.001). In the multivariate analysis, ASD closure was the only predictor of MHA occurrence after the procedure (odds ratio 7.7; 95% confidence interval 1.5 to 22; p = 0.01). In conclusion, MHA, mostly with aura, occurred in 7% of patients after transcatheter ASD-PFO closure and persisted in most of them after a mean follow-up of 2 years. ASD closure was the only independent predictor of MHA occurrence after the procedure. These results suggest that mechanisms other than device composition are involved in the occurrence of MHA in these cases.

Enhanced Thrombogenesis but Not Platelet Activation Is Associated With Transcatheter Closure of Patent Foramen Ovale in Patients With Cryptogenic Stroke

Background and Purpose— No studies have yet determined whether antiplatelet or anticoagulant therapy is the more appropriate treatment after transcatheter closure of patent foramen ovale (PFO) in patients with cryptogenic stroke. The objective of this study was to prospectively evaluate the presence, degree, and timing of activation of the platelet and coagulation systems after transcatheter closure of PFO in patients with cryptogenic stroke. Methods— Twenty-four consecutive patients (mean age, 44±10 years; 11 men) with previous cryptogenic stroke who had undergone successful transcatheter closure of PFO were included in the study. Prothrombin fragment 1+2 (F1+2) and thrombin–antithrombin III (TAT) were used as markers of coagulation activation, and soluble P-selectin and soluble CD40 ligand were used as markers of platelet activation. Measurements of all hemostatic markers were taken at baseline just before the procedure and at 7, 30, and 90 days after device implantation. Results— F1+2 and TAT levels increased from 0.41±0.16 nmol/L and 2.34±1.81 ng/mL, respectively, at baseline to a maximal value of 0.61±0.16 nmol/L and 4.34±1.83 ng/mL, respectively, at 7 days, gradually returning to baseline levels at 90 days (P<0.001 for both markers). F1+2 and TAT levels at 7 days after PFO closure were higher than those obtained in a group of 25 healthy controls (P<0.001 for both markers). Levels of soluble P-selectin and soluble CD40 ligand did not change at any time after PFO closure. Conclusions— Transcatheter closure of PFO is associated with significant activation of the coagulation system, with no increase in platelet activation markers. These findings raise the question of whether optimal antithrombotic treatment after PFO closure should be short-term anticoagulant rather than antiplatelet therapy.