Temporal Changes in Periprocedural Events in the Carotid Revascularization Endarterectomy Versus Stenting Trial.

BACKGROUND AND PURPOSE: Post-hoc, we hypothesized that over the recruitment period of the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST), increasing experience and improved patient selection with carotid stenting, and to a lesser extent, carotid endarterectomy would contribute to lower periprocedural event rates. METHODS: Three study periods with approximately the same number of patients were defined to span recruitment. Composite and individual rates of periprocedural stroke, myocardial infarction, and death rate were calculated separately by treatment assignment (carotid stenting/carotid endarterectomy). Temporal changes in unadjusted event rates, and rates after adjustment for temporal changes in patient characteristics, were assessed. RESULTS: For patients randomized to carotid stenting, there was no significant temporal change in the unadjusted composite rates that declined from 6.2% in the first period, to 4.9% in the second, and 4.6% in the third (P=0.28). Adjustment for patient characteristics attenuated the rates to 6.0%, 5.9%, and 5.6% (P=0.85). For carotid endarterectomy-randomized patients, both the composite and the combined stroke and death outcome decreased between periods 1 and 2 and then increased in period 3. CONCLUSIONS: The hypothesized temporal reduction of stroke+death events for carotid stenting-treated patients was not observed. Further adjustment for changes in patient characteristics between periods, including the addition of asymptomatic patients and a >50% decrease in proportion of octogenarians enrolled, resulted in practically identical rates. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

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.)

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.

The Carotid Revascularization Endarterectomy versus Stenting Trial: credentialing of interventionalists and final results of lead-in phase.

The success of carotid artery stenting in preventing stroke requires a low risk of periprocedural stroke and death. A comprehensive training and credentialing process was prerequisite to the randomized Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) to assemble a competent team of interventionalists with low periprocedural event rates. Interventionalists submitted cases to a multidisciplinary Interventional Management Committee. This committee evaluated 427 applicants. Of these, 238 (56%) were selected to participate in the training program and the lead-in phase, 73 (17%) who had clinical registry experience and satisfactory results with the devices used in CREST were exempt from training and were approved for the randomized phase, and 116 (27%) did not qualify for training. At 30 days in the lead-in study, stroke, myocardial infarction, or death occurred in 6.1% of symptomatic subjects and 4.8% of asymptomatic subjects. Stroke or death occurred in 5.8% of symptomatic subjects and 3.8% of asymptomatic subjects. Outcomes were better for younger subjects and varied by operator training. Based on experience, training, and lead-in results, the Interventional Management Committee selected 224 interventionalists to participate in the randomized phase of CREST. We believe that the credentialing and training of interventionalists participating in CREST have been the most rigorous reported to date for any randomized trial evaluating endovascular treatments. The study identified competent operators, which ensured that the randomized trial results fairly contrasted outcomes between endarterectomy and stenting.

Carotid artery stenting is associated with increased complications in octogenarians: 30-day stroke and death rates in the CREST lead-in phase.

BACKGROUND: A heightened risk of stroke and death among octogenarians undergoing carotid artery stenting (CAS) has been reported. The multicenter Carotid Revascularization Endarterectomy vs. Stent Trial (CREST) supported by the National Institute of Neurological Disorders, National Institutes of Health, compares the efficacy of carotid endarterectomy (CEA) and CAS in an ongoing clinical trial. This effort also includes a "lead-in" phase of symptomatic (>50% stenosis) and asymptomatic (>70% stenosis) patients. The protocol calls for patients to receive aspirin and clopidogrel before and 30-days after CAS and to be examined by a study neurologist preprocedure, at 24-hours, and at 30-day. The occurrence of stroke and death was reviewed by an independent clinical events committee. METHODS: The association of age and periprocedural stroke and death was examined in 749 lead-in patients undergoing CAS (30.7% symptomatic, 69.3% asymptomatic). Patients were separated into four age categories: less than 60, 60 to 69, 70 to 79, and 80 years or older, and the proportion of patients with stroke and death during the 30-day periprocedural period was calculated for each category. RESULTS: An increasing proportion of patients suffered stroke and death with increasing age (P = .0006); 2 (1.7%) of 120 patients under age 60, 3 (1.3%) of 229 aged 60 to 69, 16 (5.3%) of 301 aged 70 to 79, and 12 (12.1%) of 99 patients aged 80 years and older. These increasingly high complication rates at older ages were not mediated by adjustment for symptomatic status, use of antiembolic devices, gender, percentage of carotid stenosis, or the presence of distal arterial tortuosity. CONCLUSIONS: Interim results from the lead-in phase of CREST show that the periprocedural risk of stroke and death after CAS increases with age in the course of a credentialing registry. This effect is not mediated by potential confounding factors. Randomized trial data are needed to compare the CAS versus CEA periprocedural risk of stroke and death by age. Pending results from randomized studies, care should be taken when CAS is performed in older patient populations.

Credentialing of surgeons as interventionalists for carotid artery stenting: experience from the lead-in phase of CREST.

BACKGROUND: Credentialing of vascular surgeons to perform carotid artery stenting (CAS) continues to be a major issue confronting the specialty of Vascular Surgery. Cannulation of aortic arch branches, and placement of carotid antiembolic devices and stents constitute the major technical challenges to vascular surgeons becoming credentialed to perform CAS. The multicenter Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), supported by the National Institute of Neurological Disorders and Stroke, National Institute of Health, reviews credentials of interventionalists, including surgeons, for the trial's "lead-in" phase of CAS to treat symptomatic (>50% stenosis) and asymptomatic (>70% stenosis). METHODS: Vascular surgeons requesting participation in CREST must have achieved basic interventional credentialing criteria as recommended by the Society of Vascular Surgery. Each interventionalist is asked to submit notes and narrative summaries from a series of 10 to 30 CAS procedures for review by a multi-specialty review committee before being approved to participate in CREST. Thereafter, during the lead-in phase of CREST, each approved interventionalist is asked to perform CAS procedures using the study devices in as many as 20 patients. In this interim report from the CREST lead-phase, the association of specialty of operator (vascular surgeon, neurosurgeon, other specialist) and periprocedural stroke and death rate was examined in patients undergoing CAS. In addition, current enrollment volume in the lead-in phase by specialty of the principal investigator was examined. RESULTS: Thirty-two of 134 (23.9%) CREST-credentialed interventionalists are vascular surgeons (n = 22; 16.4%) or neurosurgeons (n = 10; 7.5%). For events monitored through March 31, 2004, 789 patients had undergone CAS procedures performed by these 134 specialists. Thirty-day stroke and death rate was 4.6%, and myocardial infarction was observed in 1.1% of patients. Serious adverse events have not been clustered at individual institutions, and no significant differences have been observed between vascular surgeons or neurosurgeons and other credentialed specialists. CONCLUSIONS: Vascular surgeons with basic catheter and guide wire skills, particularly those who have incorporated diagnostic cerebral angiography into their practice, can be credentialed to perform CAS. Individuals or groups should devote a number of cases (n = 10-30 per surgeon) to CAS to accomplish this goal. Pending US Food and Drug Administration approval of devices and Center for Medicaid and Medicare Services reimbursement, institutional financial support for the performance of these procedures must be secured. The learning curve for CAS should not be considered so formidable as to discourage surgeons from adding these techniques of CAS to their procedural inventory.