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Figure 1.
Unadjusted Kaplan-Meier Curves for Cumulative Mortality After the Periprocedural Period
Unadjusted Kaplan-Meier Curves for Cumulative Mortality After the Periprocedural Period

Data represent 21 603 Medicare beneficiaries undergoing carotid artery stenting, 2005-2009.

Figure 2.
Adjusted Hazards of Mortality, Stroke or Transient Ischemic Attack, and Myocardial Infarction Among Medicare Beneficiaries Undergoing Carotid Artery Stenting, 2005-2009
Adjusted Hazards of Mortality, Stroke or Transient Ischemic Attack, and Myocardial Infarction Among Medicare Beneficiaries Undergoing Carotid Artery Stenting, 2005-2009

A, Periprocedural estimates are adjusted for Elixhauser comorbidity score and past-year physician carotid artery stenting volume (N = 22 516). Estimates after the periprocedural period are adjusted for Elixhauser comorbidity score (n = 21 603). B, Periprocedural estimates are adjusted for Elixhauser comorbidity score, physician specialty, and past-year physician carotid artery stenting volume (N = 22 516). Estimates after the periprocedural period are adjusted for Elixhauser comorbidity score (n = 20 951). C, Estimates are adjusted for Elixhauser comorbidity score, past-year physician carotid artery stenting volume, census region, past-year diagnosis of angina, and number of past-year hospitalizations (N = 22 516). Limit lines indicate 95% CI. Among patients undergoing carotid artery stenting, information was missing on hospital size for 2467 patients and on hospital teaching affiliation for 515 patients.

Table 1.  
Baseline Characteristics of Medicare Beneficiaries Undergoing Carotid Artery Stenting, 2005-2009
Baseline Characteristics of Medicare Beneficiaries Undergoing Carotid Artery Stenting, 2005-2009
Table 2.  
Physician and Hospital Characteristics
Physician and Hospital Characteristics
Table 3.  
Unadjusted Risks During and After the Periprocedural Period Among Medicare Beneficiaries Undergoing Carotid Artery Stenting, 2005-2009a
Unadjusted Risks During and After the Periprocedural Period Among Medicare Beneficiaries Undergoing Carotid Artery Stenting, 2005-2009a
Table 4.  
Unadjusted Mortality Risks During and After the Periprocedural Period Among Asymptomatic and Symptomatic Medicare Beneficiaries Undergoing Carotid Artery Stenting, 2005-2009a
Unadjusted Mortality Risks During and After the Periprocedural Period Among Asymptomatic and Symptomatic Medicare Beneficiaries Undergoing Carotid Artery Stenting, 2005-2009a
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Original Investigation
March 2015

Outcomes After Carotid Artery Stenting in Medicare Beneficiaries, 2005 to 2009

Author Affiliations
  • 1Division of Pharmacoepidemiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2LASER ANALYTICA, New York, New York
  • 3Division of Vascular and Endovascular Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 4Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 5Division of Cardiovascular Medicine, Massachusetts General Hospital, Boston
  • 6Ochsner Clinical School, Ochsner Medical Center, New Orleans, Louisiana
  • 7OptumInsight Epidemiology, Waltham, Massachusetts
  • 8Division of Cardiology, Denver Veterans Affairs Medical Center, University of Colorado, Denver
  • 9Division of Cardiovascular Medicine, St Joseph Mercy Ann Arbor, Ann Arbor, Michigan
  • 10Global Health Outcomes, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana
  • 11Department of Neurology, Mayo Clinic, Jacksonville, Florida
  • 12Department of Medicine, Duke Clinical Research Institute, Durham, North Carolina
JAMA Neurol. 2015;72(3):276-286. doi:10.1001/jamaneurol.2014.3638
Abstract

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.

Introduction

Carotid artery stenting (CAS), a newer approach to the treatment of carotid stenosis, has been gaining popularity in recent years.1Quiz Ref IDFollowing the 2004 publication of the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial,2 demonstrating noninferiority of CAS relative to carotid endarterectomy among patients at high surgical risk, the Centers for Medicare & Medicaid Services (CMS) issued a National Coverage Determination3 covering CAS in Medicare beneficiaries at high surgical risk.More recently, the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST)4 established CAS as a safe and efficacious alternative to carotid endarterectomy among patients not at high surgical risk.

However, evidence from randomized clinical trials (RCTs) may not be generalizable to real-world Medicare beneficiaries, who may differ from RCT patients with regard to age,5 comorbidity burden,5 and provider-level factors.6 Physicians in the SAPPHIRE trial and CREST were enrolled only after having demonstrated CAS proficiency, defined as low complication rates with minimum volume requirements, but hands-on experience and patient outcomes among real-world physicians and hospitals are likely to be more diverse.

To our knowledge, outcomes during and beyond the periprocedural period have not been described in real-world, contemporary Medicare populations. Also, little is known about the significance of patient characteristics, clinical indications, carotid stenosis characteristics, and center characteristics outside of the RCT setting4,712 or small prospective registry or single-center or dual-center studies1316 or how these characteristics affect CAS performance beyond the periprocedural period.8,10,1315,1720 The objective of this study was to describe the incidence of outcomes overall and among subgroups of Medicare beneficiaries undergoing CAS.

Methods
Data Sources

The study was approved by the institutional review board of Brigham and Women’s Hospital, Partners Human Research Committee, and the need to obtain informed consent was waived. We conducted a retrospective cohort study using the CMS CAS database21 (CAS-D) (2005-2009), American Hospital Association Annual Survey Database (2009),22 American Medical Association Physician Masterfile (2010),23 and the denominator, institutional, noninstitutional, and vital status Medicare files (2000-2009). As a condition for CMS certification and reimbursement, facilities must submit basic clinical and procedural data on patients undergoing CAS.21 The CAS-D should capture all Medicare beneficiaries undergoing CAS at Medicare-certified facilities and has data on date of birth, CAS date, Medicare provider identification number, high surgical risk and symptomatic status, degree of carotid stenosis assessed using angiography, and embolic protection device use. These data are submitted to the CMS twice per year following the initial data submission for certification. Submissions with missing or implausible data are rejected (eMethods 1 in the Supplement).

From the CMS, we obtained claims data from January 1, 2000, to December 31, 2009, for all patients who underwent inpatient CAS between 2005 and 2009. The Medicare denominator file contains information on demographics (including race, which we categorized as white or not white), eligibility, and enrollment; the institutional file includes data on inpatient and outpatient services covered under Medicare Parts A and B; the noninstitutional file contains information on claims submitted for physician services covered under Part B; and the vital status file has information on date of death.

We linked the CAS-D to Medicare data using a highly accurate approach (eMethods 2 in the Supplement).24 We expected to link 70% to 75% of records and successfully linked 67.5%; linked and unlinked CAS records did not differ in terms of the mean patient age, degree of carotid stenosis, or proportion at high surgical risk or with symptomatic stenosis (eMethods 2 in the Supplement). We linked the American Hospital Association Annual Survey Database and American Medical Association Physician Masterfile to Medicare data using Medicare provider identifiers to obtain information on hospital organizational structure and size and physician demographic and practice data.

Study Cohort

The study cohort comprised fee-for-service Medicare beneficiaries at least 66 years old undergoing CAS with embolic protection and continuously enrolled in Medicare for at least 1 year. Patients were followed up from the CAS date until the first of the following events: the outcomes, carotid revascularization, loss of Medicare eligibility, or December 31, 2009.

Outcomes

Outcomes included death, stroke or transient ischemic attack (TIA), and myocardial infarction (MI). We obtained information on date of death from the Medicare vital status file. Stroke or TIA was defined as a diagnosis of postoperative stroke (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 997.02) during the index hospitalization or a subsequent hospitalization for ischemic stroke or TIA with a discharge diagnosis of code 433.x1, 434.x1, 435.x, or 436 in the primary or secondary position (the positive predictive value without code 435.x was 88.6%).25 Strokes were not separated from TIAs because of shared symptoms, the subjective nature of the diagnosis, the possibility of upcoding,26 and to increase algorithm sensitivity (58.6% without code 435.x). Myocardial infarctions were defined as hospitalizations for an acute MI or acute coronary syndrome (ICD-9-CM code 410.xx or 411.xx in the primary or secondary position). The positive predictive values for acute coronary syndrome were 96% for code 410 and 86% for code 411, and the positive predictive value for acute MI was 94.8%.27 The MIs occurring during the index hospitalization were assumed to have occurred after CAS.

Study Variables

Age, sex, and race data were obtained from the Medicare denominator file. The CAS-D provided data on symptomatic status, high surgical risk, and degree of carotid stenosis (eMethods 1 and eFigure 1 in the Supplement). We used the institutional and noninstitutional Medicare files in the year preceding and including the index hospital admission to identify comorbidities (eTable 1 in the Supplement) and calculate the Elixhauser comorbidity score28,29 (eMethods 3 and eTable 2 in the Supplement). Patients who underwent carotid endarterectomies in the past year were also identified (Current Procedural Terminology [Fourth Edition] code 35301). We calculated measures of health care utilization, such as the number of past-year hospitalizations, physician visits, and nursing home admissions, which may be predictive of mortality.30 Patients electively admitted for their CAS hospitalization were assumed to have undergone the procedure electively. Clinical trial enrollment was defined as being in a Medicare-approved research study (modifier code Q0, Q1, QA, QV, or QR).31 Data on physician demographics and practice characteristics were obtained from the American Medical Association Physician Masterfile, but physician specialty data were derived from the Medicare noninstitutional file. From the American Hospital Association Annual Survey Database, we categorized hospitals in terms of whether they were a teaching hospital (yes or no), hospital ownership (government, not for profit, or for profit), and size (<500 or ≥500 hospital beds). Hospitals with a stroke center were those certified by the Joint Commission as being a primary stroke center. To calculate past-year physician CAS volume, we identified performing physicians using unique identifiers in the Medicare noninstitutional file32 and selected the most experienced physician when more than 1 was listed (<3%). Physician identifiers were missing for 17.2% of CAS procedures. To calculate past-year hospital CAS volume, we identified CAS procedures using ICD-9-CM procedure codes. No institutional identifiers were missing.

Subgroups

We selected subgroups based on factors shown to affect CAS performance in the literature or based on clinical knowledge. These factors included the following: sex (male or female), symptomatic status,1520 race (white or not white), type of CAS procedure (elective or nonelective),14 age (66-69, 70-74, 75-79, or ≥80 years),12,14,15,17,19,33 clinical trial enrollment status (enrolled or not enrolled),16 and National Coverage Determination indication (high surgical risk with symptomatic carotid stenosis ≥50%, high surgical risk with asymptomatic carotid stenosis ≥80%, or none).1420 We also evaluated the effect of center characteristics on outcomes, including hospital size, teaching hospital status, presence of a stroke center, and hospital ownership.

RCT-like Cohorts and Subgroups

We applied trial-specific enrollment criteria to identify Medicare beneficiaries similar to trial patients (SAPPHIRE-like and CREST-like subgroups). Details on criteria operationalization using the CAS-D and Medicare data can be found in eTable 3, eTable 4, eMethods 4, and eMethods 5 in the Supplement.

Statistical Analysis

Baseline characteristics are reported using percentages for categorical variables and means (SDs) or medians (interquartile ranges) for continuous variables. Risks were derived from Kaplan-Meier estimators for the entire study population and for subgroups. We report crude risks (95% CIs) for outcomes during and after the periprocedural period among patients alive and without the outcome beyond the 30-day periprocedural period. To assess the association between subgroups and outcomes when accounting for clustering of patients within providers, we used frailty models.34 In multivariate analyses, we included all subgroups a priori and built our models iteratively by adding one variable at a time, retaining the strongest confounder, and repeating the process until adding covariates did not change estimates by more than 5%. All analyses were performed using statistical software (SAS, version 9.3; SAS Institute Inc).

Results
Study Population and Cohort

The cohort consisted of 22 516 patients undergoing CAS, whose procedures were performed by 1995 physicians in 749 hospitals (eFigure 2 in the Supplement). The mean patient age was 76.3 years, and most were male (60.5%) and of white race (93.8%) (Table 1). Quiz Ref IDApproximately half were symptomatic, 91.2% were at high surgical risk, and 97.4% had carotid stenosis of at least 70%. Patients undergoing CAS had a high comorbidity burden as indicated by the high prevalence of ischemic heart disease, heart failure, diabetes mellitus, peripheral artery disease, and the high proportion of patients undergoing coronary artery bypass surgery in the past year. More than one-quarter of patients were admitted nonelectively for CAS, and 18.9% were enrolled in a clinical trial. Quiz Ref IDCarotid artery stenting was performed primarily by male physicians (98.4%) specializing in cardiology (52.9%), practicing within a group (79.4%), and residing in the South (42.5%) (Table 2). The mean (SD) numbers of past-year CAS procedures performed were 13.9 (14.8) for physicians and 29.8 (25.4) for hospitals. One-third of patients underwent CAS in teaching hospitals and 55.0% in hospitals with stroke centers.

Unadjusted Risks Overall and Within Subgroups

Within 30 days of CAS, 370 patients died (1.7%; 95% CI, 1.5%-1.8%), 731 patients had a stroke or TIA (3.3%; 95% CI, 3.0%-3.5%), and 556 patients had an MI (2.5%; 95% CI, 2.3%-2.7%) (Table 3 and Figure 1). After the periprocedural period, 4096 of 21 603 patients died (32.0%; 95% CI, 31.0%-33.0%), and 1128 of 20 951 patients (9.1%; 95% CI, 8.5%-9.7%) experienced a stroke or TIA. The mean (SD) follow-up time for mortality was 747 (496) days and for stroke or TIA was 706 (503) days, with a range of follow-up extending from 1 to 1766 days for both outcomes.

Periprocedural mortality and stroke or TIA risks were highest for patients who were symptomatic (2.3% mortality and 4.3% stroke or TIA), were at least 80 years old (2.4% mortality and 4.1% stroke or TIA), were undergoing nonelective CAS (3.2% mortality and 4.5% stroke or TIA), were at high surgical risk with symptomatic carotid stenosis of at least 50% (2.4% mortality and 4.3% stroke or TIA), or underwent CAS in government-owned hospitals (2.6% mortality and 3.4% stroke or TIA), teaching hospitals (1.8% mortality and 3.7% stroke or TIA), hospitals with stroke centers (2.0% mortality and 3.5% stroke or TIA), or hospitals with at least 500 beds (1.9% mortality and 3.7% stroke or TIA) (Table 3). Periprocedural mortality risks among symptomatic patients were greater than 3% for patients at least 80 years old (3.3%), admitted nonelectively (4.1%), or treated in a government-owned hospital (4.0%); no asymptomatic patient subgroups had 30-day mortality exceeding 1.5% (Table 4).

In the more than 4 years following the periprocedural period (mean follow-up time, approximately 2 years), mortality risks exceeded one-third for patients who were 80 years or older (41.5%), symptomatic (37.3%), at high surgical risk with symptomatic carotid stenosis of at least 50% (37.3%), or admitted nonelectively (36.2%) (Table 3). Among asymptomatic patients, mortality after the periprocedural period exceeded one-third for patients at least 80 years old (Table 4). All symptomatic patients, except for those younger than 75 years, had mortality risks exceeding one-third; patients at least 80 years old (46.0%) and patients nonelectively admitted (40.4%) had the highest risks.

Adjusted Risks Within Subgroups

Older age was associated with increased hazards of periprocedural mortality and stroke or TIA, with the effect persisting beyond the periprocedural period (Figure 2). For patients at high surgical risk with symptomatic stenosis, hazards of mortality and stroke or TIA were greater than those for patients with asymptomatic carotid stenosis (≥80%) during and after the periprocedural period. During the periprocedural period, patients undergoing nonelective CAS were 2.4 (95% CI, 1.9-3.0) times more likely to die, 1.3 (95% CI, 1.1-1.5) times more likely to have a stroke or TIA, and 2.0 (95% CI, 1.7-2.4) times more likely to have an MI than patients undergoing elective CAS. Hospital characteristics, such as government ownership and the presence of a stroke center, were associated with increased adjusted hazards of mortality, and larger size was associated with increased stroke or TIA hazards; however, these effects were attenuated beyond the periprocedural period. The results were robust when we restricted the analysis to patients with an indication for CAS as per the National Coverage Determination.

Identification of and Outcomes in RCT-like Medicare Beneficiaries

Almost 80% of Medicare patients undergoing CAS met the SAPPHIRE trial indication of symptomatic stenosis of at least 50% or asymptomatic stenosis of at least 80% (eTable 3 and eMethods 4 in the Supplement). Approximately half met at least 1 of the SAPPHIRE trial high surgical risk criteria; age older than 80 years (27.4%) and the presence of clinically significant cardiac comorbidities (12.8%) were the most common criteria met. Approximately 80% of our Medicare beneficiaries were treated by physicians not meeting the SAPPHIRE trial proficiency requirements of low periprocedural complication rates and minimum number of CAS procedures. Compared with the full Medicare cohort, crude risks of periprocedural mortality (1.6%; 95% CI, 0.9%-2.3%), periprocedural stroke or TIA (2.0%; 95% CI, 1.2%-2.8%), and stroke or TIA beyond the periprocedural period (8.2%; 95% CI, 6.0%-10.4%) were slightly lower for SAPPHIRE-like Medicare beneficiaries (1307 [5.8% of the full Medicare cohort or 6.8% of the Medicare cohort without missing physician identifiers]) (eTable 5 in the Supplement).

Because most of our Medicare patients were at high surgical risk and CREST enrolled non–high-risk patients, the size of the CREST-like subgroup consisted of only 96 patients and precluded a meaningful analysis of outcome risks (eTable 5 in the Supplement). Only 15.5% and 9.3% of patients underwent CAS in centers similar to those included in CREST or by physicians meeting the CREST proficiency requirements, respectively.

Discussion

Quiz Ref IDEvidence from the SAPPHIRE trial2 and CREST4 suggests that CAS is a viable alternative to carotid endarterectomy for the prevention of stroke in the long term. Unadjusted mortality risk during a mean follow-up time of approximately 2 years in our population was 32.0%, with much higher mortality risks observed among certain subgroups. Excess periprocedural risks and the presence of significant competing risks could negate the benefits of CAS and alter the benefit-risk assessment relative to carotid endarterectomy in these patients. These findings raise questions about whether performing CAS is justified if periprocedural risks are too high or if patients do not live long enough to benefit from the main advantage of CAS, which is stroke prevention. In this study, we found that older Medicare beneficiaries, symptomatic patients, those at high surgical risk with symptomatic carotid stenosis of at least 50%, and patients undergoing CAS nonelectively were at highest risk of mortality and stroke or TIA during and after the periprocedural period. We also found that few Medicare beneficiaries underwent CAS by physicians meeting the SAPPHIRE trial or CREST proficiency requirements, either as a result of exceeding the threshold for periprocedural complication rates or of not meeting the minimum CAS volume requirements.

Investigators have estimated that carotid endarterectomy reduces the absolute 5-year stroke risk by 16% for patients with symptomatic carotid stenosis of at least 70% and by 5% for patients with symptomatic carotid stenosis of 50% to 69%.35 Assuming that CAS is associated with similar or slightly greater reductions in absolute 5-year stroke risk, the absolute benefit derived from CAS is likely to be greatly diminished or absent for patients who are at high risk of mortality from causes other than ischemic stroke. While we did not have information on cause of death, approximately 85% of patients had ischemic heart disease, about 25% had heart failure, and approximately 20% had cancer. Certain subgroups were at particularly high mortality risk during a mean follow-up of 2 years (ie, those ≥80 years and symptomatic patients), but that finding does not necessarily preclude certain patients in these subgroups from benefitting from the effect of CAS for shorter-term stroke prevention. Future research should identify factors predicting which Medicare beneficiaries may be more likely to derive benefits from CAS despite limited expected survival.

Our results may support concerns about the limited generalizability of RCT findings.5,36,37 The RCT-like Medicare subgroups consisted of younger and healthier patients than the full Medicare cohort, most were treated by physicians either exceeding periprocedural complication rates allowed in trials or not meeting minimum CAS volume requirements (>80% for the SAPPHIRE trial and >90% for the CREST), and periprocedural and late stroke or TIA risks were lower among SAPPHIRE-like Medicare beneficiaries than in the full cohort. Lower annual volume and early operator experience are associated with increased periprocedural mortality,38 and interventionalists who participated in the CREST and SAPPHIRE trial were allowed to perform CAS on randomized patients only after they had performed a sufficient number of lifetime procedures with demonstrated low periprocedural complication rates.2,4 Therefore, while requiring that providers meet certain proficiency requirements may be necessary to evaluate the efficacy of the procedure, factors affecting CAS performance, such as age, comorbidity burden, and operator skill and training, may limit the external validity of trials like the SAPPHIRE trial to the Medicare population.

The finding that few Medicare beneficiaries underwent CAS by physicians who would have met the SAPPHIRE trial or CREST enrollment criteria due to high periprocedural complication rates or low CAS volumes may be one of the factors explaining the high periprocedural mortality risk in this study (1.7% overall vs 0.7% in the CREST4 and 0.6% in the SAPPHIRE trial2). After adjusting for patient characteristics, physician specialty, and past-year physician CAS volume, we found that patients who underwent CAS at hospitals with more beds or with a stroke center or in hospitals that were government owned had higher adjusted hazards of periprocedural mortality and stroke or TIA. While these findings may result from having more complex or technically difficult cases referred to centers with these characteristics, they may also reflect variability in quality or comprehensiveness of postprocedural care.39 In our study, patient characteristics, such as older age, symptomatic status, and nonelective CAS hospitalizations, were associated with higher unadjusted and adjusted risks of periprocedural mortality and stroke or TIA. Given that the provider effect is a modifiable risk factor whose influence is likely greatest during the periprocedural period, future studies should look into provider-level factors that would optimize outcomes among older Medicare beneficiaries and among patient subgroups at particularly high risk of complications.

These findings must be interpreted in the context of certain limitations. We did not have the requisite information from the CAS-D or claims data to define all the SAPPHIRE trial and CREST enrollment criteria or to apply the criteria with the same level of detail as was done in these trials. We opted for more sensitive algorithms to operationalize trial enrollment criteria and could not measure total lifetime CAS provider volume as they did in the SAPPHIRE trial and CREST, which likely resulted in an overestimation of the numbers of Medicare patients and physicians not meeting trial enrollment criteria. We also did not identify whether physicians did not meet trial proficiency requirements due to exceeding periprocedural complication thresholds or not meeting CAS volume requirements. Although the CMS CAS-D collects information on variables that cannot be adequately defined using claims data, to our knowledge, these data have not been validated. We also could not separate strokes from TIAs or distinguish between ipsilateral and contralateral events. Last, we did not have information on cause of death, which would have enabled us to identify competing risks.

Conclusions

Our findings underscore the need for new evidence to understand the benefits of CAS outside of RCTs because few Medicare beneficiaries undergoing CAS as per the National Coverage Determination were treated by providers with proficiency levels similar to those of physicians in the SAPPHIRE trial or CREST. Quiz Ref IDPatients at higher risk of complications and mortality during and after the periprocedural period were older, had symptomatic stenosis, or underwent nonelective CAS. The decision to perform CAS should be based on overall survival as well as on the risk of complications and their effect on quality of life. The higher risk of periprocedural complications and burden of competing risks owing to age and comorbidity burden must be carefully considered when deciding between carotid stenosis treatments for Medicare beneficiaries. Real-world observational studies comparing CAS, carotid endarterectomy, and medical management are needed to determine the performance of carotid stenosis treatment options for Medicare beneficiaries.

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Article Information

Accepted for Publication: October 8, 2014.

Corresponding Author: Soko Setoguchi, MD, DrPH, Duke Clinical Research Institute, 2400 Pratt St, Durham, NC 27705 (soko@post.harvard.edu).

Published Online: January 12, 2015. doi:10.1001/jamaneurol.2014.3638.

Author Contributions: Drs Jalbert and Setoguchi had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.

Study concept and design: Jalbert, Nguyen, Gerhard-Herman, Jaff, White, Seeger, Williams, Tsai, Aronow, Johnston, Brott, Setoguchi.

Acquisition, analysis, or interpretation of data: Jalbert, Nguyen, Gerhard-Herman, Jaff, White, Rothman, Seeger, Kumamaru, Williams, Chen, Liu, Tsai, Aronow, Brott, Setoguchi.

Drafting of the manuscript: Jalbert, Setoguchi.

Critical revision of the manuscript for important intellectual content: Nguyen, Gerhard-Herman, Jaff, White, Rothman, Seeger, Kumamaru, Williams, Chen, Liu, Tsai, Aronow, Johnston, Brott, Setoguchi.

Conflict of Interest Disclosures: Dr Jaff reported being a noncompensated advisor to Abbott Vascular, Boston Scientific, Cordis Corporation, Covidien Vascular, and Medtronic Vascular; he also reported serving as a board member at VIVA Physicians, a 501(c)(3) not-for-profit education and research consortium. Dr Seeger reported being a paid consultant to OptumInsight Epidemiology and World Health Information Science Consultants, LLC. Dr Kumamaru reported being supported by the pharmacoepidemiology program at the Harvard School of Public Health, funded by Pfizer and Asisa. Dr Setoguchi reported being supported by midcareer development award grant K02-HS017731 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services; she also reported receiving research support from Johnson & Johnson and receiving personal income for consulting from Sanofi. Dr Setoguchi has made available online a detailed listing of financial disclosures (http://www.dcri.duke.edu/about-us/conflict-of-interest/). No other disclosures were reported.

Funding/Support: This project is funded by contract HHSA290-2005-0016-I-TO8 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services, as part of the Developing Evidence to Inform Decisions About Effectiveness Network and by interagency agreement contract 500-2010-00001I-TO6 and carotid endarterectomy contract 500-2010-00001I TO2 from the Centers for Medicare & Medicaid Services, US Department of Health and Human Services.

Role of the Funder/Sponsor: The manuscript was based on a report produced under contract to the Agency for Healthcare Research and Quality that was peer reviewed before it was accepted as a final report and before it was submitted for publication. Otherwise, the funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The views expressed in this article are those of the authors and do not represent policies of the Agency for Healthcare Research and Quality, Centers for Medicare & Medicaid Services, or US Department of Health and Human Services.

Previous Presentation: Preliminary results from this study were presented at the 29th Annual International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 26, 2013; Montreal, Quebec, Canada.

Additional Contributions: Marcel Salive, MD, MPH (National Institute on Aging, National Institutes of Health), Essy Mozaffari, PharmD, MPH (Sanofi), James Benenati, MD (Baptist Cardiac and Vascular Institute), and Peter Schneider, MD (Kaiser Permanente) contributed guidance and expertise by serving on the technical expert panel for this project. No member of the technical expert panel received compensation for his or her contributions.

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