Howard, George

Background: Over 9 million dual-eligible beneficiaries rely on both Medicare and Medicaid to obtain critical medical services. Medicaid serves as a safety net for low-income Medicare beneficiaries with limited assets; however, it is unknown whether dual-eligible patients have comparable outcomes for procedures to non-dual-eligible Medicare beneficiaries. We compared outcomes by dual-eligible status for patients undergoing carotid endarterectomy (CEA). Methods: We identified Medicare fee-for-service beneficiaries aged ≥65y who underwent CEA (ICD-9 38.12) from 2003-2010. Beneficiaries with ≥1m of Medicaid coverage were considered dual eligible. We fit mixed models with a random intercept for state and adjustment for demographics, comorbidities, and symptomatic status to assess the relationship between dual-eligible status and outcomes. Results: A total of 35,832 dual-eligible and 470,134 non-dual-eligible beneficiaries were hospitalized for CEA during the study period. The percentage of dual-eligible CEA patients decreased from 7.9% in 2003 to 6.7% in 2010. Dual eligibles were more likely to be younger, female, of nonwhite race, and living with comorbid conditions (e.g., heart failure, renal failure, diabetes) and symptomatic carotid disease. Dual eligibles had higher 30d composite outcomes including stroke (Table), but the associations with 1y stroke became nonsignificant from 2003-2010. Dual-eligible status was associated with higher 30d and 1y mortality after CEA throughout the study period. Conclusions: Dual-eligible Medicare-Medicaid beneficiaries had worse short-term stroke and mortality outcomes than other beneficiaries, even after adjustment for comorbidities. Our results indicate a need to understand factors contributing to poorer outcomes. Challenges include the split accountability between the two programs and the diverse sociodemographics, clinical characteristics, and generally poorer health of the patients.

Background: Administrative data such as Medicare data are commonly used for health services research and comparative effectiveness studies. These databases are readily available and a good source of long-term data on healthcare utilization and health outcomes in real-world settings. Outcomes are captured using diagnostic codes, but the evidence on the validity of these codes is scarce in contemporary Medicare data. Methods: We linked the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study data using SSN, date of birth and sex to 2003-2009 Medicare claims. In addition to the events captured by REGARDS phone interviews, medical charts were pursued for Medicare-identified strokes not previously identified in REGRADS. Events were adjudicated by stroke specialists using the retrieved medical charts. Using all the adjudicated strokes as gold standard, we calculated the sensitivity, specificity, PPV and NPV of inpatient stroke algorithms with ICD-9-CM codes [430, 431, 433.x1, 434.x1, 436] in the primary discharge diagnosis. Results: We successfully linked 15,089 REGARDS participants with mean age of 69.3, 52% female and 37% Black. We adjudicated 457 strokes, of which 48 were identified by claims only and not by interviews. The tested algorithms had high specificity (99.8-100%), PPV (88.6-90.5%) and NPV (98.9-99.9%), but low sensitivity (58.6-67.4%) (Table). Conclusions: High specificity and PPV of our algorithms to identify strokes in contemporary Medicare populations support their use in etiological and comparative effectiveness studies. While our inpatient Medicare algorithms identified 12% extra cases of strokes, their usefulness for estimating stroke incidence or related healthcare utilizations is limited by their low sensitivity. Linking cohorts to Medicare data is feasible and should be considered to increase the completeness of follow-up. Further studies are needed to evaluate more sensitive Medicare algorithms.

Background An increased risk of periprocedural stroke and death has been reported for older patients treated with carotid stenting (CAS). Selection of patients for CAS could be improved if patient or artery characteristics responsible for this higher risk could be identified. Methods The 1123 CREST patients randomized to CAS who received CAS within 30-days were analyzed. From the CREST sites, risk factors for atherosclerosis (hypertension, diabetes, and dyslipidemia) and arterial characteristics by angiography (lesion length, eccentric lesions, ulcerated lesions, and percent stenosis) were assessed. From the CREST core labs, potential mediators of the age effect included peak systolic velocity (ultrasound core, available on 853 patients) and arterial characteristics (angiographic core, available on 1042 patients, narrow/no ulcer or wide mouth, lesion location, and distal tortuosity). Mediation analysis assessed impact of adjustment for these factors on the magnitude of the estimated increased risk for CAS at older ages. Results After adjustment for sex and symptomatic status, there was a 1.72-times (95% CI: 1.26 - 2.37) increased risk of periprocedural stroke and death associated with each decade of patient age. Adjustment for lesion length as assessed in the clinical center significantly attenuated this increased risk at older ages to 1.66 (95% CI: 1.20 - 2.29, p = 0.039), an 8.3% attenuation. No other factor showed evidence as a contributor to the periprocedural increased risk of stroke and death in older patients (p > 0.10). Conclusion These data suggest that a longer carotid artery lesion length is a significant contributor to the increased risk of CAS in the elderly. However, attenuation of the age effect was modest, less than a 10% change in the hazard ratios. Other potential mediators such as tortuosity and atherosclerosis of the aortic arch and great vessels were not assessed. Non-anatomic factors that are more common with advancing age such as cerebral white matter disease and subclinical dementia were also not assessed and may play a role in how elderly patients respond to ischemic insults.

Background: We have previously reported that carotid artery stenting (CAS) carries a higher stroke risk than carotid endarterectomy (CEA) in patients over the age of 70. The question arises if advanced age is a surrogate for other factors? If so, can those factors be separately identified such that advanced chronological age alone would not be considered a contra-indication for CAS? Here we consider whether the CAS/CEA choice could be guided by other factors known in the clinical center at the time of patient evaluation, independent of age, in order to provide optimal 4-year outcomes. Methods: Demographic factors (age, sex and race), symptomatic status, patient risk factors (hypertension, diabetes, dyslipidemia, smoking), and arterial characteristics (percent stenosis) were available on 2,502 patients. Additional detailed arterial characteristics (ulcerated plaque, distal tortuosity, sequential lesions, circumferential calcification) were available on 1141 CAS and 438 CEA patients. Potential differential treatment efficacy was assessed by the addition of factor-by-treatment interaction terms to a proportional hazard model containing established predictors of outcome (treatment, symptomatic status, sex, age and age-by-treatment interaction). Results: No other factor was found to mitigate advanced age with evidence of additional treatment effect modification of 4-year outcome (p > 0.10). Discussion: Beyond the previously described differential treatment efficacy by age, there were no other patient or arterial characteristic detected to identify patient subgroups that would differentially benefit from the choice of CAS versus CEA. Our inability to identify factors to guide treatment choices could be due to the low number of stroke and death events, incomplete information regarding arterial characteristics in the CEA population, or the potential exclusion of “high risk” groups (such as those with severe arterial tortuosity) from the study.

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) enrolled 2502 patients between December of 2000 and mid-July of 2008. We analyzed temporal changes in outcomes for both CEA and CAS over the course of this study. Methods Enrollment was divided into 3 consecutive epochs (5 years, 14 months, and 16 months), each with approximately 834 patients ( Table ). Rates for the primary outcome of death, stroke, and myocardial infarction (DSMI) and for death and stroke (DS) during the periprocedural period were calculated. Poisson regression was used to adjust rates for age, sex, dyslipidemia, and symptomatic status, all of which were found to influence outcomes. Results For CAS, there was a 26% decline in DSMI (6.2% → 4.6%) and a 35% decline in DS (5.5% → 3.6%). For both composite endpoints in CEA there was no consistent pattern ( Table ). As CREST progressed, it enrolled younger patients, more men, patients more likely to be dyslipidemic and enrolled more asymptomatic patients (all p < 0.05). Adjustment for these changes mediated the improvement in event rates for the CAS patients, and had no consistent effect on CEA event rates ( Table ). Conclusion Periprocedural safety for CAS improved over time in CREST. Changes were inconsistent for CEA. Improvements for CAS in part appear to reflect changes in patient selection related to age, sex, and risk factors, as adjustment for those variables attenuated the decline in rates. Linking rates to operator experience was not feasible because of the large number of new interventionalists and surgeons entering CREST over time.

Abstract Background The multicenter prospective CREST‐2 Registry (C2R) provides recent experience in performing carotid artery stenting (CAS) for interventionists to ensure safe performance of CAS. Objective To determine the periprocedural safety of CAS performed using a transradial approach relative to CAS performed using a transfemoral approach. Methods Patients with ≥70% asymptomatic and ≥50% symptomatic carotid stenosis, ≤80 years of age and at standard or high risk for carotid endarterectomy (CEA) are eligible for the C2R. The primary endpoint was a composite of severe access‐related complications. Comparisons were made using propensity‐score matched logistic regression. Results The mean age of the cohort was 67.6 ± 8.2 years and 1906 (35.1%) were female. Indications for CAS included 4063 (74.9%) for primary atherosclerosis. A total of 2868 (52.8%) cases underwent CAS for asymptomatic disease. Transradial access was used in 213 (3.9%) patients. The transradial cohort had lower use of general anesthesia (1.5% vs. 6.3%, p = 0.007) and higher use of distal embolic protection (96.7% vs. 89.4%, p = 0.0004). There were no significant differences between radial and femoral access groups in terms of a composite of major access‐related complications (0% vs. 1.1%) or a composite of periprocedural stroke or death (3.3% vs. 2.4%; OR = 1.4 [confidence intervals 0.6, 3.1]; p = 0.42). Conclusion We found no significant differences in rates of major access‐related complications or periprocedural stroke or death with CAS performed using transradial compared to transfemoral access. Our results support incorporation of the transradial approach to clinical trials comparing CAS to other revascularization techniques.

Background: Carotid endarterectomy (CEA) is the leading procedure for carotid stenosis, yet national data on trends in rates and outcomes are limited. We determined CEA rates among Medicare beneficiaries and evaluated mortality and readmission over 8 years. Methods: We used Medicare fee-for-service data to identify beneficiaries aged ≥65y who had their first CEA (ICD-9 38.12) from 2003-2010 and calculated annual rates per 100,000 person-years (PY). We fit mixed models to assess trends in patient-level outcomes, adjusting for demographics, comorbidities, and symptomatic status. We also evaluated hospital-level trends by calculating risk-standardized mortality (RSMR) and readmission (RSRR) rates. A spatial mixed model adjusted for age, sex, and race was fit to calculate county-specific risk-standardized CEA rates in 2003-2004. Results: There were 505,966 unique CEA hospitalizations. The annual number of CEA discharges decreased from 81,604 in 2003 to 47,597 in 2010 (42% decrease), though the patient characteristics remained largely similar. The national CEA rate was 283 per 100,000 PY in 2003, and there was considerable geographic variability (Figure A). This rate decreased each year to a low of 172 per 100,000 PY in 2010. The rate of stroke or death within 30 days decreased from 3.2 to 2.7%, with a significant adjusted annual reduction of 3% (Figure B). Annual reductions in other short- and long-term outcomes were similar, ranging from 2-3%. The median hospital-level 30-day RSMR decreased over time from 0.99 to 0.57%, while the variation between hospitals increased (interquartile range of 0.7-1.67 percentage points). The 30-day RSRR decreased from 11.0 to 10.1%, but there was more homogeneity across hospitals and years. Conclusions: CEA use among Medicare patients decreased dramatically from 2003-2010, while mortality and readmission outcomes improved. The relative importance of biological and sociological mechanisms for these trends merits further study.

Background: Carotid revascularization was addressed by NASCET and ACAS. NASCET showed a 2-year stroke and death of 32.3% in medical patients and a 15.8% incidence in surgical patients (16.5% absolute/51% relative reduction). Similarly, ACAS revealed an 11% 5-year risk in medical patients and 5.1% in surgical patients (5.9% absolute reduction/53% relative reduction). Absolute risk (rather than relative risk) reduction is of prime interest to the patient. However, in these studies, treatment efficacy was assessed on a relative basis, and these procedures were equally efficacious (51% vs. 53% relative risk). The higher event rates in the symptomatic patients resulted in a larger absolute risk reduction in NASCET (16.5% vs. 5.9%). CREST is the only carotid revascularization study to include both symptomatic and asymptomatic patients undergoing CEA or carotid artery stenting (CAS), and we looked at absolute and relative risks associated with both procedures. Methods: Treatment differences in CREST by symptomatic status were reviewed and interaction terms analyzed. Results: Symptomatic periprocedural stroke and death rates were 6% for CAS vs. 3.2% for CEA (2.8% absolute/47% relative difference/p = 0.02), and were 2.5% for CAS vs. 1.4% for CEA (1.2% absolute/53% relative difference/p = 0.15) for asymptomatic. While treatment differences in periprocedural rates were significant for symptomatic but not asymptomatic patients, there was no difference in treatment efficacy as determined by relative risk reduction. Even the most prominent interaction terms were clearly not significant, p > 0.38. Discussion: There is no evidence of a CAS-CEA difference in treatment efficacy by symptomatic status in CREST. There are significant findings in symptomatic patients. This is likely a product of an increased background rate of events in this strata. While symptomatic status can identify a subgroup with an increased background rate, other factors (e.g. age or stenosis) could identify subgroups of asymptomatic patients with high event rates and large absolute treatment differences.

Background: Stroke symptoms in the general population are common (≈18% of adults 45+) and are associated with future stroke. These symptoms may also identify a broad spectrum of clinically-undetected vascular conditions. Methods: Stroke symptoms (sudden weakness, numbness, unilateral or general loss of vision, and loss of ability to communicate or understand) and time to self-reported hospitalization for any cardiovascular (CVD) reason (heart, stroke, or TIA) or stroke were assessed in the REGARDS Study (a national, population-based, longitudinal study of 30,239 African-American and white adults > 45 years enrolled 2003-2007). The symptom-hospitalization association was assessed by proportional hazards analysis in persons stroke/TIA-free at baseline, with adjustment for demographics (age, race and sex), further adjustment for SES (income and education), CVD risk factors (smoking, hypertension, diabetes, dyslipidemia, atrial fibrillation and heart disease), and “perceived health status.” Results: Over an average follow-up of 5.6 years, presence of any stroke symptom was associated with greater risk of hospitalization for stroke (11% versus 6%; HR = 1.68; 95% CI: 1.52 - 1.85), a risk only modestly attenuated by adjustment for SES (HR = 1.59; 95% CI: 1.44 - 1.76), risk factors (HR = 1.44; 95% CI: 1.29 - 1.60), and perceived health (HR = 1.37; 95% CI: 1.23 - 1.53). However, presence of any stroke symptom was more strongly related to hospitalization for CVD (42% vs. 24%; HR = 1.92; 95 CI: 1.82 - 2.03), only modestly mediated by adjustment for SES (HR = 1.82; 95% CI: 1.73 - 1.93), risk factors (HR = 1.66; 95% CI: 1.57 - 1.76), and perceived health (HR = 1.57; 95% CI: 1.48 - 1.66). Conclusions: Stroke symptoms appear to be a marker not only for stroke risk, but also for general CVD. Simple questions can identify 18% of the general population that have over a 40% chance of hospitalization for CVD over a 5-year horizon. Implications for potential intervention to reduce risk are profound.