Search

Background: Silent brain infarcts are common in patients at increased risk of stroke and are associated with a poor prognosis. In patients with asymptomatic carotid stenosis, similar adverse associations were claimed, but the impact of previous infarction or symptoms on the beneficial effects of carotid endarterectomy is not clear. Our aim was to evaluate the impact of prior cerebral infarction in patients enrolled in the Asymptomatic Carotid Surgery Trial, a large trial with 10-year follow-up in which participants whose carotid stenosis had not caused symptoms for at least six months were randomly allocated either immediate or deferred carotid endarterectomy. Methods: The first Asymptomatic Carotid Surgery Trial included 3120 patients. Of these, 2333 patients with baseline brain imaging were identified and divided into two groups irrespective of treatment assignment, 1331 with evidence of previous cerebral infarction, defined as a history of ischemic stroke or transient ischemic attack>6 months prior to randomization or radiological evidence of an asymptomatic infarct (group 1) and 1002 with normal imaging and no prior stroke or transient ischemic attack (group 2). Stroke and vascular deaths were compared during follow-up, and the impact of carotid endarterectomy was observed in both groups. Results: Baseline characteristics of patients with and without baseline brain imaging were broadly similar. Of those included in the present report, male gender and hypertension were more common in group 1, while mean ipsilateral stenosis was slightly greater in group 2. At 10 years follow-up, stroke was more common among participants with cerebral infarction before randomization (absolute risk increase 5.8% (1.8-9.8), p=0.004), and the risk of stroke and vascular death was also higher in this group (absolute risk increase 6.9% (1.9-12.0), p=0.007). On multivariate analysis, prior cerebral infarction was associated with a greater risk of stroke (hazard ratio=1.51, 95% confidence interval: 1.17-1.95, p=0.002) and of stroke or other vascular death (hazard ratio=1.30, 95% confidence interval: 1.11-1.52, p=0.001). At 10 years, greater absolute benefits from immediate carotid endarterectomy were seen in those patients with prior cerebral infarction (6.7% strokes immediate carotid endarterectomy vs. 14.7% delayed carotid endarterectomy; hazard ratio 0.47 (0.34-0.65), p=0.003), compared to those lower risk patients without prior cerebral infarction (6.0% vs. 9.9%, respectively; hazard ratio 0.61 (0.39-0.94), p=0.005), though it must be emphasized that the first Asymptomatic Carotid Surgery Trial was not designed to test this retrospective and non-randomized comparison. Conclusions: Asymptomatic carotid stenosis patients with prior cerebral infarction have a higher stroke risk during long-term follow-up than those without prior cerebral infarction. Evidence of prior ischemic events might help identify patients in whom carotid intervention is particularly beneficial. [ABSTRACT FROM AUTHOR]

Background and purpose Accumulating evidence suggests that carotid plaque vulnerability can be used as a determinant of ischemic stroke risk stratification and carotid intervention. Novelmarkers of high-risk carotidplaquein patients areneeded. Summary of review Advances in cellular and molecular pathophysiology, the demand for accurately predicting carotid risk, and choosing the optimal prevention strategy are stimulating great interest in the development of novel surrogate markers. Biomarkers in cardiovascular disease are expected to predict the natural history, clinical outcomes, and the efficacy of disease-modifying interventions. We aimed to review the literature regarding clinical data on novel serum biomarkers related to ischemic cerebrovascular events associated with carotid artery disease. We provide background information on the biomarkers related to all aspects of carotid disease: natural history, carotid intervention strategies for symptomatic and asymptomatic patients, perioperative risk prediction, and their therapeutic implications. Conclusion At present, heterogeneous data support evidence that biological markers can help existing practices to more accurately assess patients at risk for stroke. Randomized- controlled trials for carotid artery disease and carotid intervention, incorporating biomarkers, are needed. [ABSTRACT FROM AUTHOR]

Rationale Carotid endarterectomy (CEA) and medical therapy were shown superior to medical therapy alone for symptomatic (≥50%) and asymptomatic (≥60%) stenosis. Carotid angioplasty stenting (CAS) offers a less invasive alternative. Establishing safety, efficacy, and durability of CAS requires rigorous comparison with CEA in symptomatic and asymptomatic patients. Aims The objective is to compare the efficacy of CAS versus CEA in patients with symptomatic (≥50%) or asymptomatic (≥60%) extracranial carotid stenosis. Design The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) is a prospective, randomized, parallel, two-arm, multi-center trial with blinded endpoint adjudication. Primary endpoints are analyzed using standard time-to-event statistical modeling with adjustment for major baseline covariates. Primary analysis is on an intent-to-treat basis. Study Outcomes The primary outcome is the occurrence of any stroke, myocardial infarction, or death during a 30-day peri-procedural period, and ipsilateral stroke during follow-up of up to four years. Secondary outcomes include restenosis and health-related quality of life. [ABSTRACT FROM AUTHOR]

Background The Carotid Revascularization Endarterectomy versus Stenting Trial ( CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Aims Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Methods Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Results Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Conclusions Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. [ABSTRACT FROM AUTHOR]

In this article the author discusses the significant role of endovascular treatment in managing severe carotid artery stenosis despite the lack of evidence for its efficacy and safety from clinical trials. He looks into the risks of carotid artery stenting (CAS) that uses a random effect model, the long-term efficacy of stenting, and periprocedural risks after stenting. He mentions the importance of performing the intervention safely, improving technique, and the patient selection information.