Carotid Artery Stenting: JACC State-of-the-Art Review.

Significant advances in the field of carotid artery stenting (CAS) have occurred, including new randomized trial data, recent professional societal statements for competency, new techniques and new devices that have been developed, and perhaps most importantly, our understanding of how to better select candidates for CAS to avoid periprocedural complications. The current Centers for Medicare and Medicaid Services coverage decision regarding CAS is outdated, and our review supports our recommendation to approve CAS in selected candidates who are symptomatic with a carotid stenosis ≥50% and ≤99% and for asymptomatic patients with carotid stenosis ≥70% and ≤99% for stroke prevention. Optimized CAS strategies have allowed experienced operators to better assess procedure risk before CAS and have led to continued improvement in CAS outcomes. New technologies including enhanced embolic protection devices and dual-layered stents should result in further improvement.

Editor's Choice - Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials.

OBJECTIVE: Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. METHODS: The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. RESULTS: A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2 = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p = .019). CONCLUSION: Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

Outcomes after carotid endarterectomy among elderly dual Medicare-Medicaid-eligible patients.

OBJECTIVE: To determine whether patients who are dual eligible for Medicare and Medicaid benefits have outcomes after carotid endarterectomy (CEA) that are comparable to the outcomes of those eligible for Medicare alone. METHODS: The study cohort included fee-for-service Medicare beneficiaries ≥65 years of age who underwent CEA (ICD-9-CM code 38.12) between 2003 and 2010. Beneficiaries with ≥1 month of Medicaid coverage were considered dual eligible. We fit mixed models to assess the relationship between coverage (dual eligible vs Medicare only) and outcomes over time after adjustment for demographic and clinical characteristics. RESULTS: There were 53,773 dual-eligible and 452,182 Medicare-only beneficiaries hospitalized for CEA. The percentage of dual-eligible patients receiving CEA increased from 10.1% in 2003 to 11.5% in 2010, with no change in geographic distribution across the country. In adjusted analyses, dual-eligible vs Medicare-only beneficiaries had a higher rate of 30-day ischemic stroke or death; higher in-hospital, 30-day, and 1-year all-cause mortality; and higher 30-day all-cause readmission. Relative annual reductions in outcomes from 2003 to 2010 ranged from 2% to 5%, but there was no significant interaction between dual-eligible status and time. CONCLUSIONS: Dual-eligible beneficiaries had worse outcomes than those eligible for Medicare alone. Additional work is necessary to understand the reasons for this difference.

Carotid Endarterectomy and Carotid Artery Stenting in the US Medicare Population, 1999-2014.

Importance: Carotid endarterectomy and carotid artery stenting are the leading approaches to revascularization for carotid stenosis, yet contemporary data on trends in rates and outcomes are limited. Objective: To describe US national trends in performance and outcomes of carotid endarterectomy and stenting among Medicare beneficiaries from 1999 to 2014. Design, Setting, and Participants: Serial cross-sectional analysis of Medicare fee-for-service beneficiaries aged 65 years or older from 1999 to 2014 using the Medicare Inpatient and Denominator files. Spatial mixed models adjusted for age, sex, and race were fit to calculate county-specific risk-standardized revascularization rates. Mixed models were fit to assess trends in outcomes after adjustment for demographics, comorbidities, and symptomatic status. Exposures: Carotid endarterectomy and carotid artery stenting. Main Outcomes and Measures: Revascularization rates per 100 000 beneficiary-years of fee-for-service enrollment, in-hospital mortality, 30-day stroke or death, 30-day stroke, myocardial infarction, or death, 30-day all-cause mortality, and 1-year stroke. Results: During the study, 937 111 unique patients underwent carotid endarterectomy (mean age, 75.8 years; 43% women) and 231 077 underwent carotid artery stenting (mean age, 75.4 years; 49% women). There were 81 306 patients who underwent endarterectomy in 1999 and 36 325 in 2014; national rates per 100 000 beneficiary-years decreased from 298 in 1999-2000 to 128 in 2013-2014 (P < .001). The number of patients who underwent stenting ranged from 10 416 in 1999 to 22 865 in 2006 (an increase per 100 000 beneficiary-years from 40 in 1999-2000 to 75 in 2005-2006; P < .001); by 2014, there were 10 208 patients who underwent stenting and the rate decreased to 38 per 100 000 beneficiary-years (P < .001). Outcomes improved over time despite increases in vascular risk factors (eg, hypertension prevalence increased from 67% to 81% among patients who underwent endarterectomy and from 61% to 70% among patients who underwent stenting) and the proportion of symptomatic patients (all P < .001). There were adjusted annual decreases in 30-day ischemic stroke or death of 2.90% (95% CI, 2.63% to 3.18%) among patients who underwent endarterectomy and 1.13% (95% CI, 0.71% to 1.54%) among patients who underwent stenting; an absolute decrease from 1999 to 2014 was observed for endarterectomy (1.4%; 95% CI, 1.2% to 1.5%) but not stenting (-0.1%; 95% CI, -0.5% to 0.4%). Rates for 1-year ischemic stroke decreased after endarterectomy (absolute decrease, 3.5% [95% CI, 3.2% to 3.7%]; adjusted annual decrease, 2.17% [95% CI, 2.00% to 2.34%]) and stenting (absolute decrease, 1.6% [95% CI, 1.2% to 2.1%]; adjusted annual decrease, 1.86% [95% CI, 1.45%-2.26%]). Additional improvements were noted for in-hospital mortality, 30-day stroke, myocardial infarction, or death, and 30-day all-cause mortality as well as within demographic subgroups. Conclusions and Relevance: Among fee-for-service Medicare beneficiaries, the performance of carotid endarterectomy declined from 1999 to 2014, whereas the performance of carotid artery stenting increased until 2006 and then declined from 2007 to 2014. Outcomes improved despite increases in vascular risk factors.

Carotid Stenting Versus Carotid Endarterectomy: What Did the Carotid Revascularization Endarterectomy Versus Stenting Trial Show and Where Do We Go From Here?

Although rapidly expanding in its use, carotid artery stenting remains a relatively new procedure. Its growth is due, at least in part, to the perceived advantages of a less invasive technique. However, the clinical effectiveness and specific role for stenting in the treatment of carotid occlusive disease are still under evaluation. The primary aim of the randomized clinical trial, Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), was to contrast the relative efficacy of carotid stenting versus carotid endarterectomy in preventing stroke, myocardial infarction, or death during a 30-day periprocedural period or ipsilateral stroke over the follow-up period in patients with symptomatic and asymptomatic extracranial carotid stenosis. The secondary goals were to describe the differential efficacy of the 2 procedures in men and women, contrast periprocedural (30-day) morbidity and postprocedural morbidity and mortality, estimate and contrast the restenosis rates of the 2 procedures, evaluate differences in measures of health-related quality of life and cost-effectiveness, and identify subgroups of participants at differential risk of stenting or surgery. This report summarizes the results obtained from CREST with respect to its primary and secondary aims.

Comparative Effectiveness of Carotid Artery Stenting Versus Carotid Endarterectomy Among Medicare Beneficiaries.

BACKGROUND: Effectiveness of carotid artery stenting (CAS) relative to carotid endarterectomy (CEA) among Medicare patients has not been established. We compared effectiveness of CAS versus CEA among Medicare beneficiaries. METHODS AND RESULTS: We linked Medicare data (2000-2009) to the Society for Vascular Surgery's Vascular Registry (2005-2008) and the National Cardiovascular Data Registry's (NCDR) Carotid Artery Revascularization and Endarterectomy Registry (2006-2008/2009). Medicare patients were followed up from procedure date until death, stroke/transient ischemic attack, periprocedural myocardial infarction, or a composite end point for these outcomes. We derived high-dimensional propensity scores using registry and Medicare data to control for patient factors and adjusted for provider factors in a Cox regression model comparing CAS with CEA. Among 5254 Society for Vascular Surgery's Vascular Registry (1999 CAS; 3255 CEA) and 4055 Carotid Artery Revascularization and Endarterectomy Registry (2824 CAS; 1231 CEA) Medicare patients, CAS patients had a higher comorbidity burden and were more likely to be at high surgical risk (Society for Vascular Surgery's Vascular Registry: 96.7% versus 44.5%; Carotid Artery Revascularization and Endarterectomy Registry: 71.3% versus 44.7%). Unadjusted outcome risks were higher for CAS. Mortality risks remained elevated for CAS after adjusting for patient-level factors (hazard ratio, 1.24; 95% confidence interval, 1.06-1.46). After further adjustment for provider factors, differences between CAS and CEA were attenuated or no longer present (hazard ratio for mortality, 1.13; 95% confidence interval, 0.94-1.37). Performance was comparable across subgroups defined by sex and degree of carotid stenosis, but there was a nonsignificant trend suggesting a higher risk of adverse outcomes in older (>80) and symptomatic patients undergoing CAS. CONCLUSIONS: Outcomes after CAS and CEA among Medicare beneficiaries were comparable after adjusting for both patient- and provider-level factors.

Relationship Between Physician and Hospital Procedure Volume and Mortality After Carotid Artery Stenting Among Medicare Beneficiaries.

BACKGROUND: Clinical trials demonstrated the efficacy of carotid artery stenting (CAS) relative to carotid endarterectomy when performed by physicians with demonstrated proficiency. It is unclear how CAS performance may be influenced by the diversity in CAS and non-CAS provider volumes in routine clinical practice. METHODS AND RESULTS: We linked Medicare claims to the Centers for Medicare and Medicaid Services' CAS Database (2005-2009). We assessed the association between 30-day mortality and past-year physician (0, 1-4, 5-9, 10-19, ≥20) and hospital (<10, 10-19, 20-39, ≥40) CAS volumes and past-year hospital coronary and peripheral stenting volumes (<200, 200-399, 400-849, ≥850) among beneficiaries at least 66 years of age. Unadjusted 30-day mortality risk was 1.8% (95% confidence interval [CI], 1.6-2.0) for 19 724 patients undergoing CAS by 2045 physicians in 729 hospitals. Median past-year CAS volume was 9 (interquartile range, 4-19) for physicians and 23 (interquartile range, 12-41) for hospitals. Compared to physicians performing ≥20 CAS in the past year, lower CAS volumes were associated with higher adjusted risks of 30-day morality (P value for trend < 0.05): 1.4 (95% CI, 0.9-2.3) for 0 past-year CAS, 1.3 (95% CI, 0.9-1.8) for 1 to 4, 1.1 (95% CI, 0.8-1.6) for 5 to 9, and 0.9 (95% CI, 0.7-1.4) for 10 to 19. An inverse relationship between 30-day mortality and past-year CAS hospital volume as well as past-year hospital non-CAS volume, past-year hospital non-CAS volume, and 30-day mortality was also noted. CONCLUSIONS: Among Medicare patients, an inverse relationship exists between physician and hospital CAS volumes and hospital non-CAS stenting volume and 30-day mortality, even after adjusting for all pertinent patient- and hospital-level factors.

Outcomes after carotid artery stenting in Medicare beneficiaries, 2005 to 2009.

IMPORTANCE: Despite increased carotid artery stenting (CAS) dissemination following the 2005 National Coverage Determination, to our knowledge, periprocedural and long-term outcomes have not been described among Medicare beneficiaries. OBJECTIVE: To describe the incidence of outcomes during and after the periprocedural period among Medicare beneficiaries undergoing CAS. DESIGN, SETTING, AND PARTICIPANTS: Observational study with a mean follow-up time of approximately 2 years among 22,516 fee-for-service Medicare beneficiaries at least 66 years old undergoing CAS (2005-2009) who were linked to the Centers for Medicare & Medicaid Services' CAS database. Database procedure dates were required to fall during a Medicare hospitalization for CAS. MAIN OUTCOMES AND MEASURES: Periprocedural (30-day) and long-term risks of mortality and stroke or transient ischemic attack, as well as periprocedural myocardial infarction. Subgroups were based on sociodemographic, clinical, and center-level factors, as well as the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial or Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) enrollment criteria. RESULTS: The mean patient age was 76.3 years, 60.5% were male, 93.8% were of white race, 91.2% were at high surgical risk, 47.4% were symptomatic, and 97.4% had carotid stenosis of at least 70%. Crude 30-day mortality, stroke or transient ischemic attack, and myocardial infarction risks were 1.7% (95% CI, 1.5%-1.8%), 3.3% (95% CI, 3.0%-3.5%), and 2.5% (95% CI, 2.3%-2.7%), respectively. Mortality during a mean follow-up time of 2 years was 32.0% (95% CI, 31.0%-33.0%), with rates of 37.3% (95% CI, 35.8%-38.7%) among symptomatic patients and 27.7% (95% CI, 26.4%-28.9%) among asymptomatic patients. Older age, symptomatic carotid stenosis, and nonelective hospital admission were associated with increased adjusted hazards of mortality and stroke or transient ischemic attack during and after the periprocedural period. The presence of a stroke center, government ownership, and a hospital bed capacity of 500 or more were associated with increased adjusted hazards of periprocedural mortality and stroke or transient ischemic attack. Few patients met the SAPPHIRE trial or CREST enrollment criteria primarily because physicians did not meet proficiency requirements either due to exceeding periprocedural complication trial thresholds or not meeting minimum CAS volume requirements. CONCLUSIONS AND RELEVANCE: Competing risks may limit the benefits of CAS in certain Medicare beneficiaries, particularly among older and symptomatic patients who have higher periprocedural and long-term mortality risks. The generalizability of trials like the SAPPHIRE or CREST to the Medicare population may be limited, underscoring the need to evaluate real-world effectiveness of carotid stenosis treatments.

Validity of claims-based stroke algorithms in contemporary Medicare data: reasons for geographic and racial differences in stroke (REGARDS) study linked with medicare claims.

BACKGROUND: The accuracy of stroke diagnosis in administrative claims for a contemporary population of Medicare enrollees has not been studied. We assessed the validity of diagnostic coding algorithms for identifying stroke in the Medicare population by linking data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study to Medicare claims. METHODS AND RESULTS: The REGARDS Study enrolled 30 239 participants ≥45 years in the United States between 2003 and 2007. Stroke experts adjudicated suspected strokes, using retrieved medical records. We linked data for participants enrolled in fee-for-service Medicare to claims files from 2003 through 2009. Using adjudicated strokes as the gold standard, we calculated accuracy measures for algorithms to identify incident and recurrent strokes. We linked data for 15 089 participants, among whom 422 participants had adjudicated strokes during follow-up. An algorithm using primary discharge diagnosis codes for acute ischemic or hemorrhagic stroke (International Classification of Diseases, Ninth Revision, Clinical Modification codes: 430, 431, 433.x1, 434.x1, 436) had a positive predictive value of 92.6% (95% confidence interval, 88.8%-96.4%), a specificity of 99.8% (99.6%-99.9%), and a sensitivity of 59.5% (53.8%-65.1%). An algorithm using only acute ischemic stroke codes (433.x1, 434.x1, 436) had a positive predictive value of 91.1% (95% confidence interval, 86.6%-95.5%), a specificity of 99.8% (99.7%-99.9%), and a sensitivity of 58.6% (52.4%-64.7%). CONCLUSIONS: Claims-based algorithms to identify stroke in a contemporary Medicare cohort had high positive predictive value and specificity, supporting their use as outcomes for etiologic and comparative effectiveness studies in similar populations. These inpatient algorithms are unsuitable for estimating stroke incidence because of low sensitivity.

Financial management of a large multisite randomized clinical trial.

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.

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

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.

Interventions to increase enrollment in a large multicenter phase 3 trial of carotid stenting vs. endarterectomy.

BACKGROUND: Randomized clinical trials often encounter slow enrollment. Failing to meet sample size requirements has scientific, financial, and ethical implications. AIMS: We report interventions used to accelerate recruitment in a large multicenter clinical trial that was not meeting prespecified enrollment commitments. METHODS: The Carotid Revascularization Endarterectomy vs. Stenting Trial began randomization in December 2000. To accelerate enrollment, multiple recruitment tactics were initiated, which included expanding the number of sites, hiring a recruitment director (May 2003), broadening eligibility criteria (April 2005), branding with a study logo, Web site, and recruitment materials, increasing site visits by study leadership, sending e-mails to the site teams after every enrollment, distributing electronic newsletters, and implementing investigator and coordinator conferences. RESULTS: From December 2000 through May 2003, 14 sites became active (54 patients randomized), from June 2003 through April 2005, 44 sites were added (404 patients randomized), and from May 2005 through July 2008, 54 sites were added (2044 patients randomized). During these time intervals, the number of patients enrolled per site per year was 1·5, 3·6, and 5·6. For the single years 2004 to 2008, the mean monthly randomization rates per year were 19·7, 38·1, 56·4, 53·0, and 54·7 (annualized), respectively. Enrollment was highest after recruitment tactics were implemented: 677 patients in 2006, 636 in 2007, and 657 in 2008 (annualized). The prespecified sample size of 2502 patients, 47% asymptomatic, was accomplished on July 2008. CONCLUSIONS: Aggressive recruitment tactics and investment in a full-time recruitment director who can lead implementation may be effective in accelerating recruitment in multicenter trials.

The Carotid Revascularization Endarterectomy vs. Stenting Trial completes randomization: lessons learned and anticipated results.

The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) completed randomization on July 18, 2008. Sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), the trial has enrolled 2,522 participants across North America and is the largest randomized clinical trial (RCT) comparing the efficacy of carotid artery stenting (CAS) to carotid endarterectomy (CEA). It is also the largest RCT to assess carotid revascularization in both symptomatic and asymptomatic patients with carotid artery stenosis. Conventional-risk patients with symptomatic carotid stenosis (> or =50% by angiography, > or =70% by ultrasound) or asymptomatic carotid stenosis (> or =60% by angiography, > or =70% by ultrasound) were randomized to both treatment arms in a 1:1 ratio. Eligibility criteria for CREST were similar to those of the previous NINDS-sponsored CEA RCTs. The investigational devices used in the CAS arm of the study are the RX Acculink stent and the RX Accunet embolic protection system, (Abbott Vascular, Santa Clara, Calif). The primary aim is to contrast the efficacy of CAS versus CEA in preventing stroke, myocardial infarction, and all-cause mortality during a 30-day peri-procedural period, and ipsilateral stroke over the follow-up period (extending up to four years). The secondary aims are to contrast the efficacy of CAS and CEA in men and women, the restenosis rates of the two procedures, health-related quality of life, and cost effectiveness of CAS and CEA. The conclusion of enrollment in CREST marks the end of a long recruitment period from 117 community and academic hospital centers across the United States and Canada. Each surgeon and interventionalist underwent a rigorous credentialing process that included performance-assessment of prior CEA and CAS procedures. Credentialing of interventionalists also included a review of additional CAS procedures enrolled into a CREST lead-in phase prior to entering patients into the randomized trial; 1564 patients were enrolled in the lead-in, the final pathway for the largest credentialing effort to date for any clinical trial. CREST will provide long-term follow-up after carotid revascularization based on systematic ultrasonographic and neurologic surveillance, and on quality of life and cost-effectiveness comparisons between CAS and CEA in the setting of a RCT. We present a brief description of the CREST protocol, impediments that were overcome during the trial, salient results from the lead-in phase of the trial, a summary of enrollment activities and characteristics of the final cohort, and a timeline for anticipated results from the randomized phase.

Brain injury after cardiopulmonary arrest and its assessment with diffusion-weighted magnetic resonance imaging.

OBJECTIVE: To characterize the frequency and pattern of diffusion-weighted imaging (DWI) abnormalities detected as part of brain magnetic resonance imaging (MRI) and their association with short-term neurologic outcomes in patients successfully resuscitated after cardiopulmonary arrest (CPA). PATIENTS AND METHODS: We retrospectively analyzed a case series of patients who experienced CPA between May 1, 2000, and April 29, 2004, at St Luke's Hospital in Jacksonville, Fla. Eligible patients required treatment by the Code Blue team and had 1 DWI study before discharge or death. Two neuroradiologists jointly classified DWI abnormalities by anatomic location. Outcome was measured by Cerebral Performance Category score. RESULTS: Resuscitation was performed 628 times during the 48-month study period. Of 514 CPA survivors, 18 (3.5%) had MRI studies. The median age was 62 years (interquartile range [IQR], 49-73), and 10 were men. Median code duration was 16 minutes (IQR, 11-19 minutes), and median code-to-scan time was 72 hours (IQR, 28-229 hours). A DWI abnormality was noted in 9 (50%) of 18 patients. Cortical areas (global and regional) were the most common sites of restricted diffusion. Diffusion-weighted imaging abnormalities were present in 7 (70%) of 10 patients with a poor neurologic outcome at discharge. CONCLUSION: Magnetic resonance imaging is performed rarely after survival of CPA. In this study with limited sample size, a greater proportion of patients with normal DWI findings had a good neurologic outcome at the time of hospital discharge vs those with abnormal findings. Prospective studies of early and serial MRI (with DWI) are needed to confirm this association and to clarify the prognostic usefulness of such studies.

Carotid artery stenting versus carotid endarterectomy: current status.

As operator experience and device technology continue to improve, the theoretic advantages of endovascular approaches to treat carotid occlusive disease may be closer to realization. Currently, data from controlled trials of CAS is minimal, but several multicenter RCTs comparing CAS to CEA are recruiting patients actively and preliminary results show procedural morbidity and mortality rates for CAS that compare favorably to CEA. Community-based experience with CAS continues to grow and further refinements in patient selection based on plaque morphology and other variables offer further hope that endovascular approaches to carotid occlusive disease may benefit selected patients. Given the proved efficacy and durability of CEA for treatment of extracranial carotid stenosis, surgical revascularization remains the recommended standard of care for most patients. CAS will have to be proved equivalent or superior to surgery and as cost-effective to facilitate its widespread acceptance as a treatment alternative for carotid occlusive disease.

Organizing the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): National Institutes of Health, Health Care Financing Administration, and industry funding.

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) is a prospective, randomized, multicenter clinical trial of carotid endarterectomy (CEA) versus carotid artery stenting (CAS) as prevention for stroke in patients with symptomatic stenosis greater than or equal to 50%. CREST is sponsored by the US National Institute of Neurological Disorders and Stroke (NINDS) of the US National Institutes of Health (NIH), with additional support by a device manufacturer, and will provide data to the US Food and Drug Administration (FDA) for evaluation of a stent device. Because of budget constraints for CREST, Health Care Financing Administration (HCFA) reimbursement for hospital costs incurred by CREST patients will be essential. The involvement of academic scientists, industry, and three separate government agencies (NIH, FDA, HCFA) has presented many challenges in conducting the trial. A review of the pathways followed to meet these challenges may be helpful to others seeking to facilitate sharing of the costs and burdens of conducting innovative clinical research.