Background and Purpose— We report patient enrollment and retention by race and ethnicity in the CREST (Carotid Revascularization Endarterectomy Versus Stent Trial) and assess potential effect modification by race/ethnicity. In addition, we discuss the challenge of detecting differences in study outcomes when subgroups are small and the event rate is low. Methods— We compared 2502 patients by race, ethnicity, baseline characteristics, and primary outcome (any periprocedural stroke, death, or myocardial infarction and subsequent ipsilateral stroke up to 10 years). Results— Two hundred forty (9.7%) patients were minority by race (6.1%) or ethnicity (3.6%); 109 patients (4.4%) were black, 32 (1.3%) Asian, 2332 (93.4%) white, 11 (0.4%) other, and 18 (0.7%) unknown. Ninety (3.6%) were Hispanic, 2377 (95%) non-Hispanic, and 35 (1.4%) unknown. The rate of the primary end point for all patients was 10.9%±0.9% at 10 years and did not differ by race or ethnicity ( P inter >0.24). Conclusions— The proportion of minorities recruited to CREST was below their representation in the general population, and retention of minority patients was lower than for whites. Primary outcomes did not differ by race or ethnicity. However, in CREST (like other studies), the lack of evidence of a racial/ethnic difference in the treatment effect should be interpreted with caution because of low statistical power to detect such a difference. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00004732.

Background and Purpose— The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines. Methods— We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. Results— Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, −$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. Conclusions— Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique Identifier: NCT00004732.

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).

Background: The CREST trial demonstrated that for patients at standard risk of surgical complications, there was no significant difference in the primary composite outcome of periprocedural death, MI, or stroke, or late ipsilateral stroke between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although CAS had a higher rate of stroke, and CEA had a higher rate of MI. The economic implications of these two strategies are unknown. Methods: We performed a prospective health economic study alongside the CREST trial. Costs were assessed from the perspective of the US health care system in 2008 dollars using a combination of resource-based and event-based methods. Costs for carotid revascularization procedures were based on measured resource use and unit costs derived from a sample of study hospitals. Non-procedural costs for these hospitalizations were estimated using hospital billing data (charges) and cost-center-specific cost-to-charge-ratios. Costs for follow-up events were estimated using national average DRG reimbursements. The primary analysis was based on a modified intention-to-treat population for which the assigned procedure was attempted (n=1212 CAS; 1193 CEA). Results: CAS was associated with higher total procedural costs (Δ=$675, see Table), driven mainly by higher costs for disposable supplies. Length of stay was shorter for CAS, with associated reductions in non-procedural hospital costs (Δ = -$436). Total cost for the index hospitalization remained slightly higher for CAS (Δ=$239) with similar differences at 1 year. Conclusions: For patients at standard risk of surgical complications, total 1-year costs are slightly higher for CAS vs. CEA, driven largely by higher initial procedural costs. Cost-utility analysis will be performed to determine whether differences in quality of life observed in CREST render CAS an economically attractive strategy. CAS (n= 1212) CEA (n=1193) Δ CAS - CEA (95% CI via bootstrap) Index Procedure Costs, $ Excluding MD Fees 6782 ± 1412 5743 ± 1370 1039 (926, 1148) MD Fees 1114 ± 240 1478 ± 108 -364 (-379, -349) Total 7896 ± 1551 7221 ± 1450 675 (555, 800) Index Hospital Stay 7159 ± 5108 7595 ± 7482 -436 (-951, -59) TOTAL Index Hosp Costs 15055 ± 5539 14816 ± 7709 239 (-302, 778) Index Hosp LOS (days) ICU LOS 0.7 ± 1.1 0.8 ± 1.4 -0.1 (-0.24, -0.04) Non-ICU LOS 1.9 ± 3.2 2.2 ± 4.1 -0.2 (-0.55, 0.06) TOTAL LOS 2.6 ± 3.3 3.0 ± 4.5 -0.4 (-0.7, -0.06) 1-year Rehosp Costs: Repeat Revasc - CAS 295 ± 2097 273 ± 2126 -21 (-142, 201) Repeat Revasc - CEA 287 ± 2088 477 ± 2510 -190 (-371, -11) Ipsilateral Stroke 556 ± 3273 384 ± 2580 172 (-75, 402) TIA 48 ± 520 33 ± 487 16 (-25, 56) Death 63 ± 846 45 ± 779 18 (-49, 85) TOTAL Rehosp costs 1321 ± 4827 1293± 4502 28 (-334, 396) TOTAL 1-year costs 16375 ± 7730 16108 ± 9030 267 (-366, 961)

Purpose: To evaluate the efficacy and safety of 0.1 mmol/kg gadodiamide administration for contrast-enhanced magnetic resonance angiography (CE-MRA) in detecting hemodynamically relevant main stenosis (ie, >= 50% or occlusion) of aortoiliac arteries.Materials and Methods: In a multicenter, phase 3. controlled study, patients with suspected or proven peripheral arterial occlusive disease (PAOD) underwent CE-MRA with administration of gadodiamide. Intraarterial digital subtraction angiography (IA-DSA) was used as the reference. The study was approved by all Institutional Review Boards or Institutional Ethic Committees prior to commencement of patient recruitment and written informed consent was obtained from all patients.Results: Independent readers rated 25%-45% of CE-MRA images as excellent compared with 0.3%-6% of noncontrast MRA images. Mean imaging acquisition time for CE-MRA was <1 minute (0.7 +/- 1.9 minutes) versus 10 minutes (10.8 +/- 3.0) for noncontrast MRA. Sensitivity, specificity, and accuracy of CE-MRA were superior compared with those of noncontrast MRA in detecting significant arterial stenoses. Compared with IA-DSA, the sensitivity of CE-MRA ranged from 80%-88% and the specificity from 73% to 92% for the three blinded readers. at the patient level.Conclusion: Diagnostic results with CE-MRA were superior and more consistent compared with noncontrast MRA for detecting hemodynamically relevant main stenoses in patients with suspected or proven PAOD and compared favorably with IA-DSA as a reference standard.

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.