The impact of age on in-hospital outcomes after transcarotid artery revascularization, transfemoral carotid artery stenting, and carotid endarterectomy

From the Vascular and Endovascular Surgery Society

The impact of age on in-hospital outcomes after transcarotid artery revascularization, transfemoral carotid artery stenting, and carotid endarterectomy Hanaa Dakour-Aridi, MD,a Vikram S. Kashyap, MD,b Grace J. Wang, MD,c Jens Eldrup-Jorgensen, MD,d Marc L. Schermerhorn, MD,e and Mahmoud B. Malas, MD, MHS, RPVI, FACS,a La Jolla, Calif; Cleveland, Ohio; Philadelphia, Pa; Portland, Me; and Boston, Mass

ABSTRACT Objective: Previous data showed superior outcomes of carotid endarterectomy (CEA) compared with transfemoral carotid artery stenting (TFCAS) in elderly patients because of an increased stroke risk in TFCAS-treated patients. Transcarotid artery revascularization (TCAR) with flow reversal was developed to mitigate the maneuvers at highest risk for causing stroke during TFCAS, such as manipulation of a diseased aortic arch and crossing of the carotid lesion before deployment of an embolic protection device. This study aimed to compare the association between age and outcomes after TCAR, TFCAS, and CEA. Methods: All patients undergoing carotid procedures in the Society for Vascular Surgery Vascular Quality Initiative database between 2015 and November 2018 were included. Patients were divided into three different age groups (#70 years, 71-79 years, and $80 years). In-hospital outcomes after TCAR vs TFCAS and after TCAR vs CEA were compared in each age group by introducing an interaction term between treatment type and age in the logistic regression analysis after adjustment for patients’ preoperative characteristics. Results: The study cohort included 3152 TCAR, 10,381 TFCAS, and 61,650 CEA cases. The absolute and adjusted in-hospital outcomes after TCAR did not change across the different age groups. The rates of in-hospital stroke/death after TCAR were 1.4% in patients #70 years vs 1.9% in patients 71 to 79 years and 1.5% in patients $80 years (P ¼ .55). Comparison of TCAR to CEA across different age groups showed no significant differences in outcomes, and no interaction was noted between treatment and age in predicting in-hospital stroke/death (P ¼ .80). In contrast, TCAR was associated with a 72% reduction in stroke risk (4.7% vs 1%; odds ratio [OR], 0.28; 95% confidence interval [CI], 0.12-0.65; P < .01), 65% reduction in risk of stroke/death (4.6% vs 1.5%; OR, 0.35; 95% CI, 0.20-0.62; P < .001), and 76% reduction in the risk of stroke/death/ myocardial infarction (5.3% vs 2.5%; OR, 0.24; 95% CI, 0.12-0.47; P < .001) compared with TFCAS in patients $80 years. Moreover, compared with TCAR, the odds of stroke/death after TFCAS doubled at 77 years (OR, 2.0; 95% CI, 1.4-3.0; P < .01) and tripled at 90 years (OR, 3.0; 95% CI, 1.6-5.8; P < .01; P value for the interaction ¼ .08). Conclusions: TCAR is a relatively safe procedure regardless of the patient’s age. The advantages of TCAR become more pronounced in elderly patients, with significant reductions in in-hospital stroke compared with TFCAS in patients $77 years old, independent of symptomatic status and other medical comorbidities. These findings suggest that TCAR should be preferred to TFCAS in elderly patients who are at high surgical risk. (J Vasc Surg 2020;-:1-12.) Keywords: Age; Elderly patients; Carotid artery stenosis; Carotid revascularization; Transcarotid; Transfemoral; Carotid artery stenting; Carotid endarterectomy

From the Division of Vascular and Endovascular Surgery, Department of Sur-

Presented at the Spring Meeting of the Vascular and Endovascular Surgery So-

gery, University of California San Diego, La Jollaa; the Division of Vascular Sur-

ciety at the 2019 Vascular Annual Meeting of the Society for Vascular Surgery,

gery and Endovascular Therapy, Department of Surgery, University Hospitals

National Harbor, Md, June 12-15, 2019.

Cleveland Medical Center, Clevelandb; the Division of Vascular Surgery and

Additional material for this article may be found online at www.jvascsurg.org.

Endovascular Therapy, Department of Surgery, Hospital of the University of

Correspondence: Mahmoud B. Malas, MD, MHS, RPVI, FACS, Professor in Resi-

Pennsylvania, Philadelphiac; the Division of Vascular and Endovascular Ther-

dence and Vice Chair of Surgery, Chief, Division of Vascular and Endovascular

apy, Department of Surgery, Maine Medical Center, Portlandd; and the Divi-

Surgery, University of California, San Diego, 9300 Campus Point Dr, La Jolla,

sion of Vascular and Endovascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston.e Author conflict of interest: V.S.K. is a proctor and consultant for transcarotid artery revascularization cases for Silk Road. M.L.S. receives consulting fees from

CA 92037 (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest.

Abbott Vascular, Cook Medical, Endologix, Medtronic, and Silk Road. M.B.M.

0741-5214

was a proctor for Silk Road and site principal investigator for ROADSTER I

Copyright Ó 2020 by the Society for Vascular Surgery. Published by Elsevier Inc.

and ROADSTER II and national principal investigator for the ROADSTER I

https://doi.org/10.1016/j.jvs.2019.11.037

long-term follow-up study.

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Carotid artery stenting (CAS) is a minimally invasive alternative to carotid endarterectomy (CEA) in patients who are at high surgical risk. Initially, CAS had been recommended for the treatment of carotid artery stenosis in elderly patients with a higher comorbidity profile.1 However, several randomized clinical trials have shown that CEA is safer than CAS in the elderly, probably because of their complex arch and carotid artery anatomy with increased tortuosity and atherosclerotic burden.1,2 Moreover, elderly patients are presumed to have a low cerebral reserve that potentiates the effect of a given embolic particle released during the procedure.3 The Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) showed a lower relative risk of stroke in the CAS group at younger ages and higher risk at older ages.1 This was further substantiated by a meta-analysis of three other randomized clinical trials and by a retrospective multicenter analysis of the Vascular Quality Initiative (VQI) data set.2,4 However, many elderly patients have a higher comorbidity profile, putting them at a higher surgical risk if they are to undergo CEA.5 CEA also carries the risk of cranial nerve injury, hematoma, and bleeding, and it is mostly performed under general anesthesia, which increases the risk of cardiovascular morbidity, mainly myocardial infarction (MI).1,2 Transcarotid artery revascularization (TCAR) might offer a substantial advantage to this population of patients because it avoids the need to traverse the aortic arch by directly accessing the proximal carotid artery. In addition, dynamic cerebral blood flow reversal is initiated before any lesion manipulation and carries embolic debris, released during or immediately after ballooning or stent placement, away from the cerebral circulation.6,7 Recent preliminary analyses of the Society for Vascular Surgery VQI TCAR Surveillance Project (TSP) showed half the risk of in-hospital transient ischemic attack (TIA)/stroke/death in patients undergoing TCAR compared with those undergoing TFCAS.8 On the other hand, there was no difference between TCAR and CEA.9 The aim of this study was to compare the outcomes of TCAR with those of TFCAS and CEA in elderly patients and to examine the treatment-specific impact of age on perioperative outcomes.

METHODS In 2016, the Society for Vascular Surgery in collaboration with the U.S. Food and Drug Administration and the Centers for Medicare and Medicaid Services established the TSP in an attempt to obtain more real-world data about the safety and effectiveness of TCAR performed by centers participating in the VQI.10 We reviewed prospectively collected data of all patients and compared them with those of patients who underwent TFCAS and CEA in the VQI registry between January 2015 and November 2018. The VQI is a prospectively maintained database containing patient- and procedure-specific

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ARTICLE HIGHLIGHTS d

d

d

Type of Research: Multicenter, retrospective analysis of prospectively collected Vascular Quality Initiative registry data Key Findings: Analysis of 3152 transcarotid artery revascularization (TCAR), 10,381 transfemoral carotid artery stenting (TFCAS), and 61,650 carotid endarterectomy (CEA) cases revealed in-hospital stroke/death after TCAR to be 1.4% in patients #70 years vs 1.9% in patients 71 to 79 years and 1.5% in patients $80 years (P ¼ .55). Comparison of TCAR to CEA across different age groups showed no significant differences in outcomes except that TCAR was associated with a significant decrease in cranial nerve injury. TCAR was associated with a 72% reduction in stroke risk and 65% reduction in risk of stroke/death compared with TFCAS in patients $80 years. Compared with TCAR, the odds of stroke/death after TFCAS doubled at 77 years and tripled at 90 years. Take Home Message: TCAR is safe in elderly patients. There were no significant differences in in-hospital outcomes compared with CEA, except for lower rates of cranial nerve injury. Compared with TFCAS, TCAR seems to be a safer option in the elderly and is associated with significant reductions in the odds of stroke/death and myocardial infarction.

data from participating centers across all regions of the United States and Canada.11 Clinical professionals extract patient- and procedure-related information from medical charts of the participating centers in a prospective fashion. Data validation is accomplished by comparing data entered in the VQI registry with claims data provided from the participating center on an annual basis, rectifying any inconsistencies and selection bias if found. The study was approved by the VQI Research Advisory Committee. The Institutional Review Board waived individual patient consent because this was a secondary analysis of a deidentified registry. Study population Patients between the ages of 45 and 90 years were included. The VQI codes patients aged 90 years or older as 90 years to avoid identification. Patients undergoing CAS for tandem, traumatic, or dissection lesions and those undergoing CEA with concomitant procedures were excluded. The final cohort included 3152 TCAR cases (from 174 centers), 10,381 TFCAS cases (from 269 centers), and 61,650 CEA cases (from 347 centers). Preoperative data and outcomes Data collected included demographics (age, sex, race), symptomatic status, medical comorbidities (including hypertension, diabetes mellitus, coronary artery disease

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Fig 1. Restricted cubic spline model of the odds of stroke or death, vs age in the overall cohort.

[CAD], congestive heart failure [CHF], chronic obstructive pulmonary disease [COPD], and chronic kidney disease [CKD]), prior coronary artery bypass graft or percutaneous coronary intervention, prior carotid procedures (ipsilateral CEA or CAS), degree of ipsilateral stenosis, contralateral occlusion, smoking history, and preoperative medication use (aspirin, other antiplatelet medications, statins, beta blockers, anticoagulants, angiotensin-converting enzyme inhibitors) in addition to American Society of Anesthesiologists (ASA) class, elective status, and type of anesthesia. The primary end point in this analysis was a composite of stroke and death occurring within the patient’s hospital stay. Secondary end points included individual outcomes of in-hospital mortality, stroke (ipsilateral and contralateral), MI, TIA, and cranial nerve injury. Information on mortality data is determined though linkage to the Social Security Death Index. All strokes included ipsilateral and contralateral cortical and vertebrobasilar stroke. Symptomatic status was defined as presence of ipsilateral cortical or ocular symptoms (TIA/stroke) before the intervention. TIA was defined clinically as symptoms of focal neurologic deficits lasting <24 hours, whereas stroke was defined as symptoms lasting for 24 hours or longer. These symptoms include motor or sensory loss, speech abnormality, and other new neurologic symptoms documented in the medical records as being related to the contralateral hemisphere.

Statistical analysis Analyses were performed using Stata version 14.1 statistical software (StataCorp LP, College Station, Tex). Statistical significance was accepted at a P value of <.05. Restricted cubic spline analysis was used to describe the relationship between the outcomes (in-hospital stroke/death) and the exposure variable (age) in the overall cohort. This relationship was not linear, and the knots were identified where significant changes in the slope of the curve occurred (Fig 1). When each procedure was analyzed separately, the relationship between age and adverse outcomes was linear in the TCAR group and nonlinear in TFCAS and CEA. We therefore divided patients into three different age groups (#70 years, 71-79 years, and $80 years) for ease of analysis and evaluated the outcomes of patients in each age group. Restricted cubic splines are frequently used to test the hypothesis that the relationship is not linear or to summarize a relationship that is too nonlinear to be usefully summarized by a linear relationship.12 TCAR. We first evaluated the association between age and in-hospital stroke/death in the TCAR group. Baseline characteristics and outcomes of patients undergoing TCAR were compared across the three age groups (Supplementary Tables I and II, online only). Categorical variables were reported as frequency (percentage) and continuous variables as mean 6 standard deviation or median (interquartile range). Comparison of categorical

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Table I. Baseline characteristics of patients undergoing transcarotid artery revascularization (TCAR), transfemoral carotid artery stenting (TFCAS), and carotid endarterectomy (CEA) TCAR 3152 (4.2) Age, years

74 (67-80)

TFCAS 10,381 (13.8) 70 (63-77)

CEA 61,650 (82.0) 71 (65-77)

1153 (36.6)

5404 (52.1)

29,276 (47.5)

71-79 years

1191 (37.8)

3333 (32.1)

21,520 (34.9)

$80 years

808 (25.6)

1644 (15.8)

10,854 (17.6)

Female sex

1129 (35.8)

3568 (34.4)

24,256 (39.3)

Nonwhite race

284 (9.0)

1087 (10.5)

5807 (9.4)

Symptomatic status

<.001 <.001

Age #70 years

P value

<.001 <.01 <.001

1233 (39.1)

5581 (53.8)

17,802 (28.9)

HTN

2848 (90.4)

9157 (89.3)

54,960 (89.2)

.12

DM

1173 (37.2)

3999 (38.7)

22,330 (36.2)

<.001

CAD

1633 (51.8)

3973 (38.7)

16,422 (26.7)

<.001

CHF

616 (19.5)

1714 (16.5)

6711 (10.9)

<.001

COPD

898 (28.5)

2765 (26.7)

14,163 (23.0)

<.001

CKD

1213 (39.3)

3518 (34.8)

20,575 (34.0)

<.001

Current smoker

732 (23.2)

2857 (27.6)

15,728 (25.5)

<.001

Prior ipsilateral CEA

553 (17.6)

2127 (20.5)

1141 (1.9)

<.001

Prior ipsilateral CAS

60 (1.9)

210 (2.0)

153 (0.3)

<.001

1675 (55.2)

6244 (61.3)

29,059 (48.1)

<.001

Aspirin

2826 (89.7)

8945 (86.2)

51,475 (83.5)

<.001

Statin

2779 (88.2)

8475 (81.7)

51,199 (83.1)

<.001

P2Y12 receptor antagonists

2670 (84.7)

7914 (76.3)

20,877 (33.9)

<.001

Beta blockers

1807 (57.4)

5607 (54.1)

33,672 (54.7)

.01

Anticoagulation

450 (14.3)

1179 (11.4)

6274 (10.2)

<.001

ACE inhibitors

1693 (53.7)

5311 (51.2)

32,645 (53.0)

Degree of stenosis >80% Preoperative medications

1-2 3 4-5

<.01 <.001

ASA class 157 (5.0)

2115 (22.0)

3094 (5.0)

2084 (66.2)

5931 (61.6)

45,861 (74.5)

905 (28.8)

1578 (16.4)

12,569 (20.4)

Elective procedures

2854 (90.6)

8073 (77.8)

54,100 (87.8)

<.001

General anesthesia

2584 (82.0)

1313 (12.7)

56,738 (92.1)

<.001

ACE, Angiotensin-converting enzyme; ASA, American Society of Anesthesiologists; CAD, coronary artery disease; CAS, carotid artery stenting; CHF, congestive heart failure; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; HTN, hypertension. Categorical variables are presented as number (%). Continuous variables are presented as median (interquartile range).

variables was performed using Fisher exact or Pearson c2 test; continuous variables were compared using analysis of variance or Kruskal-Wallis test for continuous variables as appropriate. Multivariable logistic regression analysis was then used to evaluate risk-adjusted in-hospital outcomes across the three age groups (reference category: age #70 years) by adjusting for variables that were significantly different between the age groups on univariable analysis and based on clinical judgment (Supplementary Table I, online only). To avoid overfitting and to ensure the most parsimonious model, we checked for multicollinearity (correlation between predictors) using variance inflation factors and goodness of

fit using the Hosmer-Lemeshow test. The final model included symptomatic status, diabetes, CAD, COPD, and CKD. TCAR vs TFCAS and TCAR vs CEA. Patients’ baseline characteristics were compared between the three procedures (Table I). In-hospital outcomes were compared between TCAR and TFCAS and between TCAR and CEA in each age group using Pearson c2 test for categorical variables and Student t-test (or Wilcoxon rank sum test) for continuous variables. To identify effect modification of procedure performance by age group, we introduced an interaction term between treatment type (TCAR vs TFCAS and TCAR vs CEA, respectively) and age group

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Percentage of Patients in Each Procedure

100 90 80 70 60

52.1

50 40

5

-

47.5 37.8

36.6

30

32.1 34.9

25.6 15.8 17.6

20 10 0 70-79

≤ 70

≥ 80

Age groups TCAR

TFCAS

CEA

Fig 2. Histogram of the percentage of patients in each procedure by age group. CEA, Carotid endarterectomy; TCAR, transcarotid artery revascularization; TFCAS, transfemoral carotid artery stenting.

(#70 years, 71-79 years, $80 years) in the multivariable logistic regression analysis. Stepwise backward and forward selection was used to identify the variables included in the final multivariable logistic models, such as sex, race, symptomatic status, hypertension, diabetes, CAD, CHF, CKD, smoking history, prior ipsilateral CEA, degree of ipsilateral stenosis, preoperative use of P2Y12 inhibitors, statin, and angiotensin-converting enzyme inhibitors in addition to elective status and type of anesthesia. We also calculated and plotted the adjusted odds ratios (ORs) of in-hospital stroke/death for the age-bytreatment interaction using postestimation commands of the multivariable logistic models. For this analysis, age was analyzed as a continuous variable to better visualize how association between adverse outcomes and treatment changed for each unit of change in age. A probability value of <.10 was determined a priori to indicate significant effect modification, which is in line with previous literature.1,4 Observations were clustered in each center to reduce the bias from unmeasurable hospital-level factors and to account for intergroup correlation. Each regression model was assessed for predictive ability using the area under the receiver operating characteristic curve and for goodness of fit using the Hosmer-Lemeshow test. A subgroup analysis comparing the outcomes of the three procedures (TCAR vs TFCAS vs CEA) in each age group was performed by stratifying with respect to symptom status.

RESULTS A total of 75,183 procedures performed in 70,702 patients were included in the final cohort: 3152 TCAR, 10,381 TFCAS, and 61,650 CEA cases. The TCAR group had a higher percentage of patients in the older age groups compared with TFCAS and CEA (Fig 2). Of 3152 patients undergoing TCAR, 37.8% were between 71 and

79 years compared with 32.1% of TFCAS patients and 34.9% of CEA patients (P < .001). On the other hand, whereas 25.6% of TCAR patients were 80 years of age or older, 15.8% of TFCAS patients and 17.6% of CEA patients were $80 years of age (P < .001). Compared with patients in the TFCAS and CEA groups, those undergoing TCAR were more likely to have CAD (51.8% vs 38.7% and 26.7%, respectively), CHF (19.5% vs 16.5% and 10.9%), and CKD (39.3% vs 34.8% and 34.0%). They were also more likely to have ASA class 4 and class 5 (28.8% vs 16.4% and 20.4%) and to undergo elective procedures (90.6% vs 77.8% and 87.8%) compared with TFCAS and CEA patients, respectively (all P <.001; Table I). On the other hand, patients in the TFCAS group were more likely to be symptomatic compared with TCAR and CEA patients (53.8% vs 39.1% and 28.9%) and to have ipsilateral stenosis >80% on duplex ultrasound (61.3% vs 55.2% and 48.1%). They were also more likely to be smokers (TFCAS, 27.6%; TCAR, 23.2%; CEA, 25.5%) and to have a history of prior CEA (TFCAS, 20.5%; TCAR, 17.6%; CEA, 1.9%; all P <.001). The majority of CEA and TCAR procedures were performed under general anesthesia (92.1% and 82.0%, respectively) compared with only 12.7% of TFCAS procedures (P < .001). Age and TCAR In the TCAR group, older patients (age $80 years) were more likely to be female (39.4% vs 37.0%; P < .01) and to have CKD (52.5% vs 27.4%; P < .001) compared with patients #70 years of age (Supplementary Table I, online only). On univariable and multivariable analysis, there was no significant difference between the three age groups in terms of in-hospital mortality, stroke, MI, and TIA. The absolute rates of the composite outcome of stroke/death were 1.4% in patients #70 years of age vs 1.9% in patients 71 to 79 years and 1.5% in patients $80 years (P ¼ .55). After adjustment for symptomatic status, diabetes, CAD, COPD, and CKD, the odds of in-hospital stroke/death were 1.5 (95% confidence interval [CI], 0.8-2.6; P ¼ .21) in the 71- to 79-year age group and 1.2 (95% CI, 0.52.7; P ¼ .67) in patients $80 years compared with patients #70 years (Supplementary Table II, online only). TCAR vs TFCAS. No significant differences in adverse outcomes were noted between TCAR and TFCAS in patients younger than 80 years, except for higher unadjusted crude rates of in-hospital mortality after TFCAS in patients aged between 71 and 79 years (1.0% vs 0.3%; P ¼ .04; unadjusted analysis, Table II). On the other hand, in patients $ 80 years of age, the rates of in-hospital mortality (2.5% vs 0.7%), stroke (4.7% vs 1.0%), stroke/TIA (5.4% vs 1.7%), stroke/death (4.6% vs 1.5%), and stroke/ death/MI (5.3% vs 2.5%) were significantly higher in TFCAS vs TCAR (all P < .01). After adjustment for sex, race, symptomatic status, diabetes, CAD, CHF, smoking history, prior ipsilateral CEA, preoperative P2Y12 inhibitors, elective status, and anesthesia

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Table II. Unadjusted absolute rates of in-hospital outcomes in transcarotid artery revascularization (TCAR) vs transfemoral carotid artery stenting (TFCAS) and TCAR vs carotid endarterectomy (CEA) across the different age groups #70 years

$80 years

71-79 years TCAR vs TFCAS

In-hospital outcomes

TCAR (n ¼ 1153)

TFCAS (n ¼ 5404)

P value

TCAR (n ¼ 1191)

TFCAS (n ¼ 3333)

P value

TCAR (n ¼ 808)

TFCAS (n ¼ 1644)

P value

Death

5 (0.4)

43 (0.8)

.25

4 (0.3)

32 (1.0)

.04

6 (0.7)

41 (2.5)

<.01

Ipsilateral stroke

11 (0.95)

33 (1.3)

.41

17 (1.4)

29 (1.8)

.46

7 (0.9)

32 (4.2)

<.001

Stroke

13 (1.1)

38 (1.5)

.41

19 (1.6)

33 (2.0)

.39

8 (1.0)

36 (4.7)

<.001

TIA

6 (0.5)

41 (0.8)

.45

34 (1.0)

.42

6 (0.7)

26 (1.6)

.08

MI Stroke/TIA

7 (0.6) 19 (1.7)

9 (0.8)

24 (0.4)

.46

5 (0.4)

20 (0.6)

.65

10 (1.2)

17 (1.0)

.65

117 (2.2)

.26

28 (2.4)

101 (3.0)

.23

14 (1.7)

89 (5.4)

<.001

Stroke/death

16 (1.4)

77 (1.4)

.92

23 (1.9)

60 (1.8)

.77

12 (1.5)

75 (4.6)

<.001

Stroke/death/Mi

22 (1.9)

96 (1.8)

.76

26 (2.2)

78 (2.3)

.76

20 (2.5)

87 (5.3)

<.01

TCAR vs CEA TCAR (n ¼ 1153)

CEA (n ¼ 29,276)

P value

TCAR (n ¼ 1191)

CEA (n ¼ 21,520)

P value

TCAR (n ¼ 808)

CEA (n ¼ 10,854)

Death

5 (0.4)

62 (0.2)

.11

4 (0.3)

55 (0.3)

.60

6 (0.7)

Ipsilateral stroke

11 (0.95)

241 (0.8)

.62

17 (1.4)

213 (1.0)

.14

7 (0.9)

127 (1.2)

Stroke

13 (1.1)

337 (1.2)

.94

19 (1.6)

281 (1.3)

.40

8 (1.0)

159 (1.5)

TIA

6 (0.5)

161 (0.6)

.89

112 (0.5)

.28

6 (0.7)

180 (0.8)

.12

10 (1.2)

108 (1.0)

.50

400 (1.9)

.23

14 (1.7)

228 (2.1)

.48

MI

63 (0.6)

.17 .44 .28 .56

161 (0.6)

.80

5 (0.4)

19 (1.7)

513 (1.8)

.79

28 (2.4)

Stroke/death

16 (1.4)

373 (1.3)

.74

23 (1.9)

316 (1.5)

.20

12 (1.5)

187 (1.7)

.62

Stroke/death/MI

22 (1.9)

518 (1.8)

.73

26 (2.2)

472 (2.2)

.98

20 (2.5)

280 (2.6)

.86

4 (0.4)

766 (2.6)

<.001

6 (0.6)

572 (2.7)

<.001

315 (2.9)

<.001

Stroke/TIA

Cranial nerve injury

7 (0.6)

9 (0.8)

45 (0.4)

P value

1 (0.15)

MI, Myocardial infarction; TIA, transient ischemic attack. Values are reported as number (%).

use, no significant association was observed between treatment (TCAR or TFCAS) and adverse outcomes in patients younger than 80 years (adjusted analysis, Table III). However, in patients $80 years, TCAR was associated with 65% lower odds of stroke/death (OR, 0.35; 95% CI, 0.20-0.62; P < .001) compared with TFCAS. Regarding the secondary outcomes, TCAR was associated with 72% lower odds of in-hospital stroke (OR, 0.28; 95% CI, 0.120.65; P < .01) and 76% lower odds of stroke/death/MI (OR, 0.24; 95% CI, 0.12-0.47; P < .001). The interaction between treatment (TCAR vs TFCAS) and age group in predicting the primary outcome of in-hospital stroke/death was statistically significant (P ¼ .01). Fig 3 shows the adjusted ORs of in-hospital stroke and stroke/death in TCAR vs TFCAS across different age values. A significant difference in the odds of in-hospital stroke and stroke/death was noted at 77 years and 69 years, respectively. Compared with TCAR, TFCAS was associated with double the odds of in-hospital stroke at 85 years and double the odds of stroke/death at 77 years. TCAR vs CEA. In the case of TCAR vs CEA, we found no significant differences in the rates of in-hospital outcomes across all age groups (Table II). The lack of significance remained after adjustment for potential

confounders including sex, race, symptomatic status, hypertension, diabetes, CAD, CHF, CKD, smoking history, prior ipsilateral CEA, degree of ipsilateral stenosis, preoperative P2Y12 inhibitors, statin and angiotensinconverting enzyme inhibitor use, and elective status. However, patients undergoing CEA had higher rates of cranial nerve injury (2.6%-2.9%) in all age groups after CEA compared with TCAR (between 0.2% and 0.6%). On adjusted analysis, TCAR was associated with almost 95% reduction in cranial nerve injury in patients aged $80 years (OR, 0.05; 95% CI, 0.01-0.32; P < .01). No significant interaction was found between treatment (TCAR vs CEA) and age groups in predicting outcomes (Table III). No significant differences were observed in the adjusted ORs of in-hospital stroke and stroke/death in TCAR vs CEA across different age groups (P ¼ .98 and P ¼.73, respectively; Fig 4). No interaction was observed between symptomatic status and treatment across the different age groups. Comparison of absolute and adjusted in-hospital outcomes between TCAR and TFCAS and between TCAR and CEA in asymptomatic and symptomatic patients $80 years of age is shown in Tables IV and V. In asymptomatic patients, TCAR had significantly lower rates of

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Table III. Adjusted in-hospital outcomes after transcarotid artery revascularization (TCAR) vs transfemoral carotid artery stenting (TFCAS) and TCAR vs carotid endarterectomy (CEA) within each age group using the treatment-age interaction

#70 years

Interaction between treatment and age groups

$80 years

71-79 years a

TCAR vs TFCAS OR (95% CI)

P value

OR (95% CI)

P value

OR (95% CI)

P value

P value

Stroke

1.00 (0.51-1.98)

.99

1.05 (0.60-1.81)

.87

0.28 (0.12-0.65)

<.01

.02

Stroke/TIA

0.81 (0.48-1.36)

.42

0.83 (0.50-1.38)

.47

0.33 (0.18-0.62)

<.01

.01

Stroke/death

0.80 (0.48-1.33)

.39

0.69 (0.43-1.11)

.13

0.35 (0.20-0.62)

<.001

.02

Stroke/death/MI

0.73 (0.40-1.35)

.32

0.81 (0.49-1.34)

.41

0.24 (0.12-0.47)

<.001

.01

TCAR vs CEAb OR (95% CI)

P value

OR (95% CI)

P value

OR (95% CI)

P value

P value

Stroke

1.05 (0.57-1.90)

.85

1.21 (0.75-1.98)

.44

0.75 (0.34-1.65)

.48

.51

Stroke/TIA

0.97 (0.61-1.52)

.88

1.25 (0.82-1.90)

.31

0.89 (0.51-1.53)

.66

.79

Stroke/death

1.02 (0.59-1.76)

.96

1.22 (0.80-1.88)

.36

0.91 (0.49-1.69)

.77

.80

Stroke/death/MI

0.86 (0.53-1.38)

.52

0.87 (0.59-1.28)

.48

0.94 (0.57-1.55)

.80

.79

Cranial nerve injury

0.16 (0.05-0.53)

<.01

0.21 (0.10-0.48)

<.001

0.05 (0.01-0.32)

<.01

.33

CI, Confidence interval; MI, myocardial infarction; OR, odds ratio; TIA, transient ischemic attack. Boldface P values signify statistically significant differneces between the two procedures. a Adjusted for sex, race, symptomatic status, hypertension, diabetes, coronary artery disease, congestive heart failure, chronic kidney disease, smoking history, prior ipsilateral carotid endarterectomy, degree of ipsilateral stenosis, preoperative P2Y12 inhibitors, statin and angiotensin-converting enzyme inhibitor use, and elective status. b Adjusted for sex, race, symptomatic status, hypertension, diabetes, coronary artery disease, congestive heart failure, chronic kidney disease, smoking history, prior ipsilateral CEA, degree of ipsilateral stenosis, preoperative P2Y12 inhibitors, statin and angiotensin-converting enzyme inhibitor use, and elective status.

in-hospital mortality compared with TFCAS (0.6% vs 3.4% [P ¼ .01]; OR, 0.20; 95% CI, 0.05-0.87; P ¼ .03). In symptomatic patients $80 years of age, the rates of stroke, stroke/death, and stroke/death/MI were significantly higher in TFCAS vs TCAR. The rates of stroke/death in symptomatic patients $80 years of age undergoing TFCAS were 5.9% compared with 1.8% in TCAR and 2.9% in CEA (P ¼ .01), with TCAR being associated with a reduction of 76% in stroke/death compared with TFCAS (OR, 0.24; 95% CI, 0.10-0.59; P < .01]. On the other hand, no difference was noted between TCAR and CEA in asymptomatic and symptomatic patients, except for the higher rates of cranial nerve injury associated with CEA (Tables IV and V).

DISCUSSION This large analysis of the VQI database demonstrates the safety of TCAR in elderly patients and its superiority to TFCAS, particularly in patients who are $77 years of age. On the other hand, there were no significant differences between TCAR and CEA across the age spectrum. This is in line with previous publications that have highlighted the favorable outcomes of TCAR in high-risk patients with carotid artery stenosis.7-9,13 The preliminary analysis of the TSP demonstrated significant reductions in the rates of in-hospital TIA/stroke/death in high-risk patients undergoing TCAR compared with TFCAS and

similar in-hospital stroke/death rates between TCAR and CEA after multivariable adjustment and rigorous matching.8,9 Our findings suggest that in elderly patients, TCAR might be a safer minimally invasive option compared with TFCAS, with similar outcomes to CEA. Of 3152 patients undergoing TCAR, 25.6% were 80 years of age or older compared with 15.8% of TFCAS patients and 17.6% of CEA patients. Patients undergoing TCAR were more likely to have major comorbidities that might put them at high surgical risk, such as CAD, CHF, CKD, and higher ASA class, compared with patients in the TFCAS and CEA groups. After adjustment for potential confounders, there was a small and nonsignificant change in the risk of stroke with increasing age among TCARtreated patients. However, compared with TFCAS, TCAR was associated with a 65% reduction in the odds of stroke/death (OR, 0.35; 95% CI, 0.20-0.62; P < .001) and with 72% and 76% reduction in the odds of in-hospital stroke (OR, 0.28; 95% CI, 0.12-0.65; P < .01) and stroke/ death/MI (OR, 0.24; 95% CI, 0.12-0.47; P < .001). The agerelated differential efficacy of TCAR compared with TFCAS was notable at 77 years and $90 years of age. The odds of in-hospital stroke and stroke/death after TFCAS vs TCAR doubled at 85 years and 77 years, respectively (Fig 3). On the other hand, no significant differences were noted between TCAR and CEA with age (Fig 4), and

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Fig 3. Adjusted odds ratios (ORs) of in-hospital stroke (left) and stroke/death (right) after transcarotid artery revascularization (TCAR) vs transfemoral carotid artery stenting (TFCAS) for age-by-treatment interaction. In each graph, the first dotted vertical line represents the age at which the odds of the outcomes in TFCAS compared with TCAR become significant. The second dotted line represents the age at which the odds of in-hospital stroke and stroke/death in TFCAS become double that in TCAR, respectively.

Fig 4. Adjusted odds ratios (ORs) of in-hospital stroke (left) and stroke/death (right) for age-by-treatment (carotid endarterectomy [CEA] vs transcarotid artery revascularization [TCAR]) interaction.

there was no evidence that the age-by-treatment relationships differed by symptom status. When TFCAS was first introduced, it was thought to be a safer option than CEA in the elderly owing to its

minimally invasive nature by avoiding general anesthesia, eliminating cranial nerve injury and wound complications, and providing better accessibility to anatomically challenging lesions.14 However, outcomes

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Table IV. Absolute proportions of outcomes in patients $80 years, stratified by symptomatic status Patients $80 years TCAR vs TFCAS TCAR (n ¼ 477)

TCAR vs CEA

TFCAS (n ¼ 647)

P value

TCAR (n ¼ 477)

CEA (n ¼ 7406)

P value .11

Asymptomatic Death

4 (0.8)

7 (1.1)

.77

4 (0.8)

27 (0.4)

Stroke

3 (0.6)

8 (3.4)

.01

3 (0.6)

71 (0.96)

.47

MI

6 (1.3)

3 (0.5)

.14

6 (1.3)

69 (0.9)

.47

Stroke/death

6 (1.3)

15 (2.3)

.19

6 (1.3)

89 (1.2)

.91

Stroke/death/MI

11 (2.3)

17 (2.6)

.73

11 (2.3)

150 (2.0)

.67

e

e

e

0

191 (2.6)

<.01

Cranial nerve injury

(n ¼ 331)

(n ¼ 995)

(n ¼ 331)

(n ¼ 3444)

Symptomatic Death

2 (0.6)

33 (3.3)

.01

2 (0.6)

18 (0.5)

.85

Stroke

5 (1.5)

28 (5.2)

.01

5 (1.5)

88 (2.6)

.24 .90

MI

4 (1.2)

14 (1.4)

1.00

4 (1.2)

39 (1.1)

Stroke/death

6 (1.8)

59 (5.9)

<.01

6 (1.8)

98 (2.9)

.27

Stroke/death/MI

9 (2.7)

69 (6.9)

.01

9 (2.7)

130 (3.8)

.33

e

e

e

1 (0.4)

123 (3.6)

<.01

Cranial nerve injury

CEA, Carotid endarterectomy; MI, myocardial infarction; TCAR, transcarotid artery revascularization; TFCAS, transfemoral carotid artery stenting. Boldface P values signifiy statistically significant differences between the two procedures.

Table V. Adjusted in-hospital outcomes in patients $80 years, stratified by symptomatic status Patients $80 years TCAR vs TFCAS

TCAR vs CEA

OR (95% CI)

P value

Death

0.63 (0.25-1.57)

.32

2.36 (0.83-6.69)

.11

Stroke

0.20 (0.05-0.87)

.03

0.63 (0.20-2.01)

.43

OR (95% CI)

P value

Asymptomatic

MI

2.31 (0.59-9.0)

.23

1.12 (0.52-2.43)

.77

Stroke/death

0.47 (0.16-1.37)

.17

1.02 (0.45-2.30)

.97

Stroke/death/MI

0.75 (0.33-1.75)

.51

1.03 (0.59-1.83)

.91

e

e

N/A 0.87 (0.20-3.69)

Cranial nerve injury Symptomatic Death

0.22 (0.09-0.53)

<.01

Stroke

0.26 (0.09-0.76)

.01

0.54 (0.19-.55)

.25

MI

0.89 (0.28-2.86)

.85

0.81 (0.29-2.30)

.70

Stroke/death

0.24 (0.10-0.59)

<.01

0.56 (0.21-1.46)

.24

Stroke/death/MI

0.31 (0.13-0.70)

.01

0.60 (0.25-1.44)

.25

e

e

0.10 (0.02-0.59)

.01

Cranial nerve injury

.85

CEA, Carotid endarterectomy; CI, confidence interval; MI, myocardial infarction; N/A, not applicable; OR, odds ratio; TCAR, transcarotid artery revascularization; TFCAS, transfemoral carotid artery stenting. Boldface P values signify statistically significant differences between the two procedures.

from several randomized clinical trials have recognized age as an important predictor of adverse outcomes after CAS, citing higher incidences of periprocedural stroke, TIA, and mortality among elderly patients and emphasizing the need to consider age in selecting the treatment option for carotid stenosis.2,15-19 In the Carotid Revascularization Endarterectomy vs Stenting Trial

(CREST), investigators found the efficacy of CAS and CEA approximately equal at age 70 years; however, better outcomes were seen with CAS in patients younger than 70 years and with CEA in those older than 70 years. The risk of the primary end point of perioperative stroke/ death/MI after CAS increased by 1.77 times (95% CI, 1.38-2.28) every 10 years (P < .001).1 A pooled analysis of

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3433 patients from the Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S), Stent-Protected Angioplasty vs Carotid Endarterectomy (SPACE), and International Carotid Stenting Study (ICSS) trials highlighted an increase in periprocedural stroke and death in TFCAS vs CEA in patients older than 70 years, but there was no significant risk difference in patients younger than 70 years.18 Similarly, a metaanalysis of pooled patient data from four randomized trials confirmed the superiority of CEA to TFCAS in patients aged 70 to 74 years and older, in which the hazard ratio of periprocedural stroke and death (between randomization and 120 days) in TFCAS vs CEA was 2.09 (1.32-3.32) for patients aged 70 to 74 years.19 A recent study by our team using the VQI database confirmed the effect modification role that age plays in the safety and efficacy of carotid revascularizations observed in a real-world setting.4 Using a large multicenter registry, the riskadjusted effectiveness of CAS was particularly sensitive to patient age, whereas CEA performance was relatively stable across various age strata. Interestingly, the observed effect was more pronounced a decade earlier than what was previously reported in the ideal setting of a randomized clinical trial.4 The significant increase in the adjusted odds of adverse outcomes after TFCAS compared with TCAR in patients $80 years of age can be attributed to the increased prevalence of severe aortic arch and target lesion calcification and ulceration in the elderly. The tortuous anatomy, the increased catheter residence time and manipulation within the aortic arch, and the need to traverse the lesion before deployment of protective devices in TFCAS considerably increase the risk of embolization from atherosclerotic plaques, rendering TFCAS a higher risk procedure in this population of patients.20-22 Alternatively, direct open cervical access of the common carotid artery during TCAR allows the surgeon to avoid crossing the atherosclerotic arch and the major vessels and to provide a CEA-like protection by clamping the common carotid artery.6,23,24 Moreover, the other main advantage of TCAR, in addition to avoiding the arch and cannulation of the common carotid artery, is the ability to perform the entire procedure (lesion crossing, ballooning, and stenting) under robust protection using dynamic flow reversal. The flow reversal technology significantly reduces the risk of stroke by removing any emboli dislodged by manipulating the lesion in the carotid artery through an extracorporeal filter, before the blood is diverted back to the femoral vein.6,23,24 In the SilkRoad Medical Embolic Protection System: First-InMan (PROOF) study, the incidence of new ipsilateral cerebral lesions observed on post-TCAR diffusion-weighted magnetic resonance imaging was 17.9%, which is lower than that reported by other studies.25 In the small randomized Prevention of Cerebral Embolization by Proximal Balloon Occlusion Compared to Filter Protection

2020

During Carotid Artery Stenting (PROFI) trial, the incidence ranged from 45% with proximal flow reversal protection with the Mo.Ma device (Medtronic/Invatec, Santa Rosa, Calif) to 87% in the distal embolic protection group. In the ICSS trial, new lesions were seen in 73% of the filter-protected TFCAS group.26 In our analysis, however, we could not account for relevant anatomic factors such as arch tortuosity, degree of calcification, or plaque characteristics because of limited data on these variables in the VQI data set. Short-term results from the Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER) study of high-risk patients undergoing TCAR with the ENROUTE neuroprotection and stent system (Silk Road Medical, Sunnyvale, Calif) showed the lowest published stroke rate (1.4%) compared with all other prospective and randomized clinical trials of endovascular carotid artery intervention.13 These positive findings persisted up to 1 year with a 0.6% incidence of ipsilateral stroke and 3.7% overall mortality after TCAR with dynamic flow reversal.7 Because of medical or anatomic risk factors, many elderly patients are not candidates for CEA; TCAR might serve as an alternative for patients who do not qualify for CEA as this study has shown no significant differences in outcomes between TCAR and CEA across the age spectrum. Observational multicenter studies are crucial to the process of generating evidence that extends beyond the scope of experimental designs to reflect contemporary practice.27 Nonetheless, our study has several limitations attributable to its retrospective design that are worth highlighting. Possible limitations include the potential for selection bias introduced by the nonrandom allocation of interventions as each procedure has its own indications and contraindications. For instance, TCAR is contraindicated in patients with diffuse or severe disease in the common carotid artery, in those with a short common carotid artery runway from the clavicle to the bifurcation (<5 cm), and if the common carotid artery diameter is # 6 mm. In these cases, CEA or TFCAS would be a safer option accordingly. Moreover, unmeasured confounders, such as the provider’s or patient’s preference, the physician’s technical skills, and centerlevel practices, might influence the procedure choice and contribute to this selection bias. For a center to participate in the VQI TSP and to perform TCAR, it has to be enrolled in the VQI CEA and CAS registries. All centers performing TCAR also perform CEA, and most also perform TFCAS. Therefore, we could confidently say that these are a subset of the larger groups of centers performing CEA and TFCAS. Moreover, in all adjusted analyses, including that comparing TCAR to TFCAS and TCAR to CEA, observations were clustered in each center to reduce the bias from unmeasurable hospital-level factors and to account for intergroup correlations. We also believe that controlling for patient-level details and

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applying several risk adjustment methods can achieve national representation of outcomes and a valid comparison between TCAR, TFCAS, and CEA in elderly patients. In addition, no formal neurologic evaluations are performed after carotid revascularization, which can lead to an under-reporting of true neurologic events. This reporting bias is common to most recent pivotal studies and is unlikely to affect our comparisons between TCAR and TFCAS or CEA within the VQI database as it applies the three procedures equally. In addition, the lack of adequate follow-up for the TCAR cohort, most of which has been entered in the past two years, limited the analysis to in-hospital outcomes. However, most adverse outcomes related to carotid revascularization tend to occur early in the hospitalization course, and several previous studies have demonstrated similar outcomes between TFCAS and CEA, except for the perioperative period, which is associated with higher rates of adverse events after TFCAS compared with CEA.

CONCLUSIONS No association between age and in-hospital outcomes after TCAR were observed in this study. The minimally invasive nature of TCAR and its advantages in entirely avoiding the aortic arch and using flow reversal make it a safe option in elderly patients. Compared with TFCAS, TCAR is associated with significant reductions in the odds of stroke and stroke/death in elderly patients, particularly in those $77 years of age. On the other hand, there were no significant differences between TCAR and CEA across the age spectrum. Longer followup is needed to study the effect of age on the longterm efficacy and durability of TCAR. The authors would like to acknowledge the contributions of Mr Farhan Hussein for helping in the literature review and statistical analysis.

AUTHOR CONTRIBUTIONS Conception and design: HDA, VK, GW, JEJ, MS, MM Analysis and interpretation: HDA, VK, GW, JEJ, MS, MM Data collection: HDA Writing the article: HDA Critical revision of the article: HDA, VK, GW, JEJ, MS, MM Final approval of the article: HDA, VK, GW, JEJ, MS, MM Statistical analysis: HDA, MM Obtained funding: Not applicable Overall responsibility: MM

REFERENCES 1. Voeks JH, Howard G, Roubin GS, Malas MB, Cohen DJ, Sternbergh WC III, et al. Age and outcomes after carotid stenting and endarterectomy: the Carotid Revascularization Endarterectomy Versus Stenting trial. Stroke 2011;42: 3484-90.

2. Carotid Stenting Trialists’ Collaboration. Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta-analysis of individual patient data. Lancet 2010;376:1062-73. 3. Chaer RA, Shen J, Rao A, Cho JS, Hamad GA, Makaroun MS. Cerebral reserve is decreased in elderly patients with carotid stenosis. J Vasc Surg 2010;52:569-75. 4. Nejim B, Alshwaily W, Aridi HD, Locham S, Goodney P, Malas M. Age modifies the efficacy and safety of carotid artery revascularization procedures. J Vasc Surg 2019;69: 1490-503. 5. Bennett KM, Scarborough JE, Shortell CK. Predictors of 30day postoperative stroke or death after carotid endarterectomy using the 2012 carotid endarterectomy-targeted American College of Surgeons National Surgical Quality Improvement Program database. J Vasc Surg 2015;61:103-11. 6. Malas MB, Leal J, Kashyap V, Cambria RP, Kwolek CJ, Criado E. Technical aspects of transcarotid artery revascularization using the ENROUTE transcarotid neuroprotection and stent system. J Vasc Surg 2017;65:916-20. 7. Malas MB, Lorenzo JI, Nejim B, Hanover TM, Mehta M, Kashyap V, et al. Analysis of the ROADSTER pivotal and extended-access cohorts shows excellent 1-year durability of transcarotid stenting with dynamic flow reversal. J Vasc Surg 2019;69:1786-96. 8. Malas MB, Dakour-Aridi H, Wang GJ, Kashyap VS, Motaganahalli RL, Eldrup-Jorgensen J, et al. Transcarotid artery revascularization versus transfemoral carotid artery stenting in the Society for Vascular Surgery Vascular Quality Initiative. J Vasc Surg 2019;69:92-103. 9. Schermerhorn ML, Liang P, Dakour-Aridi H, Kashyap VS, Wang GJ, Nolan BW, et al. In-hospital outcomes of transcarotid artery revascularization and carotid endarterectomy in the Society for Vascular Surgery Vascular Quality Initiative. J Vasc Surg 2019 Jun 18. [Epub ahead of print]. 10. Society for Vascular Surgery Vascular Quality Initiative. TransCarotid Artery Revascularization (TCAR) Surveillance Project. Available at: https://www.vqi.org/data-analysis/tcarsurveillance-project/. Accessed May 15, 2019. 11. Cronenwett JL, Kraiss LW, Cambria RP. The Society for Vascular Surgery Vascular Quality Initiative. J Vasc Surg 2012;55:1529-37. 12. Harre FE Jr, Lee KL, Pollock BG. Regression models in clinical studies: determining relationships between predictors and response. J Natl Cancer Inst 1988;80:1198-202. 13. Kwolek CJ, Jaff MR, Leal JI, Hopkins LN, Shah RM, Hanover TM, et al. Results of the ROADSTER multicenter trial of transcarotid stenting with dynamic flow reversal. J Vasc Surg 2015;62:1227-34. 14. Henry M, Amor M, Klonaris C, Henry I, Masson I, Chati Z, et al. Angioplasty and stenting of the extracranial carotid arteries. Tex Heart Inst J 2000;27:150-8. 15. Brott TG, Howard G, Howard VJ, Roubin GS, Meschia JF, Mackey A, et al. Long-term results of stenting versus endarterectomy for carotid-artery stenosis. N Engl J Med 2016;374: 1021-31. 16. Eckstein HH, Ringleb P, Allenberg JR, Berger J, Fraedrich G, Hacke W, et al. Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial. Lancet Neurol 2008;7:893-902. 17. Ederle J, Dobson J, Featherstone RL, Bonati LH, van der Worp HB, de Borst GJ, et al. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet 2010;375:985-97.

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18. Bonati LH, Fraedrich G. Age modifies the relative risk of stenting versus endarterectomy for symptomatic carotid stenosisda pooled analysis of EVA-3S, SPACE and ICSS. Eur J Vasc Endovasc Surg 2011;41:153-8. 19. Howard G, Roubin GS, Jansen O, Hendrikse J, Halliday A, Fraedrich G, et al. Association between age and risk of stroke or death from carotid endarterectomy and carotid stenting: a meta-analysis of pooled patient data from four randomised trials. Lancet 2016;387:1305-11. 20. Vos JA, van den Berg JC, Ernst SM, Suttorp MJ, Overtoom TT, Mauser HW, et al. Carotid angioplasty and stent placement: comparison of transcranial Doppler US data and clinical outcome with and without filtering cerebral protection devices in 509 patients. Radiology 2005;234:493-9. 21. Ackerstaff RG, Suttorp MJ, van den Berg JC, Overtoom TT, Vos JA, Bal ET, et al. Prediction of early cerebral outcome by transcranial Doppler monitoring in carotid bifurcation angioplasty and stenting. J Vasc Surg 2005;41:618-24. 22. Moore WS, Popma JJ, Roubin GS, Voeks JH, Cutlip DE, Jones M, et al. Carotid angiographic characteristics in the CREST trial were major contributors to periprocedural stroke and death differences between carotid artery stenting and carotid endarterectomy. J Vasc Surg 2016;63:851-8. 23. Chang DW, Schubart PJ, Veith FJ, Zarins CK. A new approach to carotid angioplasty and stenting with

24.

25.

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transcervical occlusion and protective shunting: why it may be a better carotid artery intervention. J Vasc Surg 2004;39: 994-1002. Alpaslan A, Wintermark M, Pintér L, Macdonald S, Ruedy R, Kolvenbach R. Transcarotid artery revascularization with flow reversal. J Endovasc Ther 2017;24:265-70. Pinter L, Ribo M, Loh C, Lane B, Roberts T, Chou TM, et al. Safety and feasibility of a novel transcervical access neuroprotection system for carotid artery stenting in the PROOF Study. J Vasc Surg 2011;54:1317-23. Bijuklic K, Wandler A, Hazizi F, Schofer J. The PROFI study (Prevention of Cerebral Embolization by Proximal Balloon Occlusion Compared to Filter Protection During Carotid Artery Stenting): a prospective randomized trial. J Am Coll Cardiol 2012;59:1383-9. Bergqvist D, Björck M, Säwe J, Troëng T. Randomized trials or population-based registries. Eur J Vasc Endovasc Surg 2007;34:253-6.

Submitted Jul 12, 2019; accepted Nov 11, 2019.

Supplementary material available online along with audio discussion from the 2019 Vascular Annual Meeting of the Society for Vascular Surgery at www.jvascsurg.org.

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Supplementary Table I (online only). Baseline characteristics of patients undergoing transcarotid artery revascularization (TCAR) across different age groups TCAR (n ¼ 3152) #70 years Age, years

65 (60-68)

71-79 years

$80 years

75 (73-77)

83 (81-86)

P value <.001 <.01

Female sex

426 (37.0)

385 (32.3)

318 (39.4)

Nonwhite race

124 (10.8)

87 (7.3)

73 (9.0)

.01

Symptomatic status

470 (40.8)

432 (36.3)

331 (41.0)

.04

1027 (89.1)

1078 (90.5)

743 (92.0)

.10

HTN DM

458 (39.7)

457 (38.4)

258 (31.9)

<.01

CAD

589 (51.1)

652 (54.7)

392 (48.5)

.02

CHF

227 (19.7)

240 (20.2)

149 (18.4)

.63

COPD

347 (30.1)

367 (30.8)

184 (22.8)

<.001

CKD

307 (27.4)

488 (41.9)

418 (52.5)

<.001

Current smoker

457 (39.6)

225 (18.9)

50 (6.2)

<.001

Prior ipsilateral CEA

231 (20.1)

205 (17.2)

117 (14.5)

.01

Prior ipsilateral CAS

22 (1.9)

28 (2.4)

10 (1.2)

.20

Degree of ipsilateral stenosis >80%

634 (57.2)

631 (54.9)

410 (53.0)

.19

Contralateral occlusion

162 (14.5)

96 (8.5)

50 (6.7)

<.001

Preoperative medications Aspirin

1034 (89.7)

1076 (90.3)

716 (88.6)

.46

Statin

1019 (88.4)

1058 (88.8)

702 (86.9)

.40

P2Y12 receptor antagonists

997 (86.5)

1019 (85.6)

654 (80.9)

<.01

Beta blockers

662 (57.5)

694 (58.3)

451 (55.8)

.55

Anticoagulation

130 (11.3)

176 (14.8)

144 (17.8)

<.001

ACE inhibitors

647 (56.2)

650 (54.6)

396 (49.0)

.01

63 (5.5)

59 (5.0)

35 (4.3)

3

766 (66.6)

768 (64.7)

550 (68.2)

4-5

322 (28.0)

361 (30.4)

222 (27.5)

Elective procedures

1045 (90.6)

1078 (90.5)

731 (90.5)

.99

General anesthesia

951 (82.6)

980 (82.3)

653 (80.8)

.57

ASA class 1-2

.42

ACE, Angiotensin-converting enzyme; ASA, American Society of Anesthesiologists; CAD, coronary artery disease; CAS, carotid artery stenting; CEA, carotid endarterectomy; CHF, congestive heart failure; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; HTN, hypertension. Categorical variables are presented as number (%). Continuous variables are presented as median (interquartile range).

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Supplementary Table II (online only). Unadjusted and adjusted in-hospital outcomes after transcarotid artery revascularization (TCAR) in different age groups Unadjusted

Adjusted 70-80 years

In-hospital outcomes

#70 years (n ¼ 1153)

71-79 years (n ¼ 1191)

$80 years (n ¼ 808)

P value

OR (95% CI)

#70 years

P value

$80 years OR (95% CI)

P value

Death

5 (0.4)

4 (0.3)

6 (0.7)

.41

Reference

1.1 (0.3-3.8)

.91

2.1 (0.5-8.5)

.31

Ipsilateral stroke

11 (0.95)

17 (1.4)

7 (0.9)

.41

Reference

1.6 (0.8-3.2)

.21

0.96 (0.4-2.6)

.94

Stroke

13 (1.1)

19 (1.6)

TIA

6 (0.5)

MI

.43

Reference

1.5 (0.7-3.0)

.26

0.9 (0.4-2.5)

.90

6 (0.7)

.75

Reference

1.5 (0.5-4.3)

.42

1.5 (0.5-4.8)

.47 .17

5 (0.4)

10 (1.2)

.09

Reference

0.6 (0.2-2.2)

.48

2.0 (0.8-5.2)

Stroke/TIA

19 (1.7)

28 (2.4)

14 (1.7)

.42

Reference

1.5 (0.9-2.7)

.16

1.1 (0.6-2.1)

.70

Stroke/death

16 (1.4)

23 (1.9)

12 (1.5)

.55

Reference

1.5 (0.8-2.6)

.21

1.2 (0.5-2.7)

.67

Stroke/death/MI

22 (1.9)

26 (2.2)

20 (2.5)

.69

Reference

1.2 (0.7-2.1)

.51

1.4 (0.8-2.6)

.27

4 (0.4)

6 (0.6)

1 (0.2)

.41

Reference

1.4 (0.3-6.6)

.62

0.4 (0.03-4.1)

.40

Cranial nerve injury

7 (0.6)

8 (1.0)

9 (0.8)

CI, Confidence interval; MI, myocardial infarction; OR, odds ratio; TIA, transient ischemic attack. Unadjusted values are reported as number (%).