Brott, Thomas G.

Rationale: Asymptomatic carotid stenosis is commonly seen in medical practice. CREST-2 is a pair of concurrent two-arm multi-site randomized trials of intensive medical management versus intensive medical management in combination with revascularization by endarterectomy or stenting. It is not known how often patients entering the trials have opportunities for further risk factor reduction at study entry and whether these opportunities vary across trial centers. Methods: Baseline data on 683 patients from 109 clinical sites were used for these analyses. We determined the rates of control at baseline for systolic blood pressure (SBP), defined as <140 mmHg (or ≥140 with >15mmHg orthostatic drop), and low density lipoprotein (LDL), defined as <70 mg/dl. We then tested differences in these baseline control rates by site-related characteristics, including site type, StrokeNet site vs. not, specialty of site Principal Investigator (PI), type of hospital, central vs local IRB, type of research team and whether site is enrolling in one or both trials. P-value <0.05 was considered significant. Results: At baseline, the mean SBP was 140.4±20.5 mmHg, but only 62% of participants were in target. The mean LDL at baseline was 83.7±36.9, mg/dl, with 42% in target. None of the site characteristics were associated with a higher level of control for SBP at baseline. The only characteristic associated with having a higher level of LDL control was sites enrolling in only the CAS trial (57%) compared to those enrolling in the CEA only (24%) or in both trials (42%) (p=0.02). Conclusions: Opportunities to improve on risk factors are common among CREST-2 participants, but site characteristics did not predict the likelihood of being at goal for SBP while sites enrolling in only the CAS trial had a higher level of LDL control.

Rationale For patients with asymptomatic high-grade carotid stenosis, clinical investigations have focused on preventing cerebral infarction, yet stenosis that reduces cerebral blood flow may independently impair cognition. Whether revascularization of a hemodynamically significant carotid stenosis can alter the course of cognitive decline has never been investigated in the context of a randomized clinical trial. Hypothesis Among patients randomized in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis (CREST-2) trials, the magnitude of treatment differences (revascularization versus medical management alone) with regard to cognition will differ between those with flow impairment compared to those without flow impairment. Sample size We will enroll approximately 500 patients from CREST-2, of which we anticipate 100 will have hemodynamic impairment. We estimate 93% power to detect a clinically meaningful treatment difference of 0.5 SD. Methods and design We will use perfusion-weighted magnetic resonance imaging to stratify by hemodynamic status. Linear regression will compare treatment differences, controlling for baseline cognitive status, age, depression, prior cerebral infarcts, silent infarction, white matter hyperintensity volume, and cerebral microbleeds. Study outcomes The primary outcome is change in cognition at one year. Secondary outcomes include silent infarction, change in white matter hyperintensity volume, number of cerebral microbleeds, and cortical thickness over one year. Discussion If cognitive impairment can be shown to be reversible by revascularization, then we can redefine “symptomatic carotid stenosis” to include cognitive impairment and identify a new population of patients likely to benefit from revascularization. Trial Registration US National Institutes of Health (NIH) clinicaltrials.gov NCT03121209

Background and Purpose— Prediction models may help physicians to stratify patients with high and low risk for periprocedural complications or long-term stroke risk after carotid artery stenting or carotid endarterectomy. We aimed to evaluate external performance of previously published prediction models for short- and long-term outcome after carotid revascularization in patients with symptomatic carotid artery stenosis. Methods— From a literature review, we selected all prediction models that used only readily available patient characteristics known before procedure initiation. Follow-up data from 2184 carotid artery stenting and 2261 carotid endarterectomy patients from 4 randomized trials (EVA-3S [Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis], SPACE [Stent-Protected Angioplasty Versus Carotid Endarterectomy], ICSS [International Carotid Stenting Study], and CREST [Carotid Revascularization Endarterectomy Versus Stenting Trial]) were used to validate 23 short-term outcome models to estimate stroke or death risk ≤30 days after the procedure and the original outcome measure for which the model was developed. Additionally, we validated 7 long-term outcome models for the original outcome measure. Predictive performance of the models was assessed with C statistics and calibration plots. Results— Stroke or death ≤30 days after the procedure occurred in 158 (7.2%) patients after carotid artery stenting and in 84 (3.7%) patients after carotid endarterectomy. Most models for short-term outcome after carotid artery stenting (n=4) or carotid endarterectomy (n=19) had poor discriminative performance (C statistics ranging from 0.49–0.64) and poor calibration with small absolute risk differences between the lowest and highest risk groups and overestimation of risk in the highest risk groups. Long-term outcome models (n=7) had a slightly better performance with C statistics ranging from 0.59 to 0.67 and reasonable calibration. Conclusions— Current models did not reliably predict outcome after carotid revascularization in a trial population of patients with symptomatic carotid stenosis. In particular, prediction of short-term outcome seemed to be difficult. Further external validation of existing prediction models or development of new prediction models is needed before such models can be used to support treatment decisions in individual patients.

OBJECTIVE The overall risk of ischemic stroke from a chronically occluded internal carotid artery (COICA) is around 5%–7% per year despite receiving the best available medical therapy. Here, authors propose a radiographic classification of COICA that can be used as a guide to determine the technical success and safety of endovascular recanalization for symptomatic COICA and to assess the changes in systemic blood pressure following successful revascularization. METHODS The radiographic images of 100 consecutive subjects with COICA were analyzed. A new classification of COICA was proposed based on the morphology, location of occlusion, and presence or absence of reconstitution of the distal ICA. The classification was used to predict successful revascularization in 32 symptomatic COICAs in 31 patients, five of whom were female (5/31 [16.13%]). Patients were included in the study if they had a COICA with ischemic symptoms refractory to medical therapy. Carotid artery occlusion was defined as 100% cross-sectional occlusion of the vessel lumen as documented on CTA or MRA and confirmed by digital subtraction angiography. RESULTS Four types (A–D) of radiographic COICA were identified. Types A and B were more amenable to safe revascularization than types C and D. Recanalization was successful at a rate of 68.75% (22/32 COICAs; type A: 8/8; type B: 8/8; type C: 4/8; type D: 2/8). The perioperative complication rate was 18.75% (6/32; type A: 0/8 [0%]; type B: 1/8 [12.50%]; type C: 3/8 [37.50%], type D: 2/8 [25.00%]). None of these complications led to permanent morbidity or death. Twenty (64.52%) of 31 subjects had improvement in their symptoms at the 2–6 months’ follow-up. A statistically significant decrease in systolic blood pressure (SBP) was noted in 17/21 (80.95%) patients who had successful revascularization, which persisted on follow-up (p = 0.0001). The remaining 10 subjects in whom revascularization failed had no significant changes in SBP (p = 0.73). CONCLUSIONS The pilot study suggested that our proposed classification of COICA may be useful as an adjunctive guide to determine the technical feasibility and safety of revascularization for symptomatic COICA using endovascular techniques. Additionally, successful revascularization may lead to a significant decrease in SBP postprocedure. A Phase 2b trial in larger cohorts to assess the efficacy of endovascular revascularization using our COICA classification is warranted.

Background and Purpose: Management of carotid stenosis remains controversial despite several trials evaluating carotid endarterectomy (CEA) and carotid angioplasty/stenting (CAS). We compared attitudes in the management of carotid stenosis between selected experts within Europe and North America. Methods: A 3-phase Delphi survey was e-mailed to select stroke experts from Europe (n = 390) and North America (n = 289). Those completing the initial survey were shown all responses after each survey round. Consensus was defined as ≥80% agreement. Results: For phases 1, 2, and 3, response rates were 32%, 62%, and 73%, respectively. Overall, 100 (15%) of 679 participated in all 3 phases, 19% Europeans versus 9% North Americans ( P = .0007). The European group reached consensus in 6 of 15 statements; The North American group reached consensus in 4 of 15. Ninety percentage of Europeans versus 70% of North Americans ( P = .017) stated CEA is superior to CAS for symptomatic carotid stenosis. This difference was not significant in the final model (adjusted odds ratio: 3.72 [95% confidence interval: 0.95-14.5]). Sixty-nine percentage of North Americans agreed there is a stronger indication for CAS over CEA in patients younger than 65 years for symptomatic carotid stenosis, whereas 55% of Europeans ( P = .023) disagreed. For asymptomatic carotid stenosis, when asked how likely they would recommend CAS, 62% North Americans said “sometimes” versus 60% of Europeans said “never” ( P = .06). Conclusion: The majority of North American and European respondents did not consider the 2 procedures equivalent and seemed to indicate that CEA was preferred for the management of carotid stenosis. These findings need to be further explored to help establish evidence-based guidelines.