Carotid Endarterectomy, TransFemoral Carotid Artery Stenting

and TransCarotid Artery Revascularization (TCAR) – Data From

The SVS Vascular Quality Initiative (VQI)

MAHMOUD MALAS, MD, MHS, RPVI, FACSProfessor and Chief Vascular and Endovascular Surgery

Vice Chair of Surgery for Clinical ResearchUniversity of California San Diego

Professor of Epidemiology Johns Hopkins Bloomberg School of Public Health

Presenter Disclosure InformationMahmoud B. Malas Principal Investigator

1. CREST 2. ACT I3. CAPTURE II4. CHOICE5. FREEDOM6. ROADSTER

7. SAPHIRE W8. ROADSTER II9. CREST II10.CREST Companion Study11. CREST H12. ROADSTER Long-Term Follow up Study

• National/International Principal Investigator for “The ROADSTER Long Term Follow Up”

Grube E. et al, Am Journal Cardiol 2006;

Endpoint CAS CEA Risk Ratio (95% CI)

P

Stroke or death to 120 days, No. (%)

153 (8.9)

99 (5.8)

1.53 (1.20 – 1.95)

.001

Meta-Analysis of SPACE, EVA-3S, and ICSS

CAS vs. CEA Hazard Ratio 95% CI P-Value

Stroke 4.1 vs. 2.3% HR = 1.79; 95% CI: 1.14-2.82 0.01

MI 1.1 vs. 2.3% HR = 0.50; 95% CI: 0.26-0.94 0.03

CAS vs. CEA Hazard Ratio, 95% CI P-Value7.2 vs. 6.8% HR = 1.11; 95% CI: 0.81-1.51 0.51

Peri-procedural Stroke and MI

Primary Endpoint ≤ 4 years

Carotid Endarterectomy

(CEA)65 years: Gold standard

82%of

procedures

Low stroke rates & Higher surgical morbidity

Crossing the aortic arch

Crossingthe lesion

Trans-Femoral Carotid Artery Stenting

(TF-CAS)15 years on Market

HIGH (2x) peri-procedural stroke risk

18%of

procedures

CREST CNI2: 2.1% CNI unresolved at 6 months (80% motor)CREST MI1: 2.3% CEA vs 1.1% TF CAS

CREST 30-day All Stroke1: 2.3% CEA vs 4.1% TF CAS

1 CREST Trial: N Engl J Med 2010;363:11-23 2 Circulation. 2012;125:2256-2264

Mis-Aligned Distal Filters

TFCAS vs. CEA

Crossing the

lesion

Crossing the aortic arch

Stroke after TFCAS

ICSS: Silent DWI Lesions After CAS

MRI Diffusion Weighted AbnormalitiesAssessed 1 to 7 days after the procedure

CAS(n = 108)

CEA(n = 92)

HR(95% CI)

P

DWI lesions

50(46.3%)

13(14.1)

5.24(2.61-10.3) 0.001

Surgically Inspired CEA-like Neuroprotection

ENROUTE® TransCarotid Neuroprotection & Stent System

TCAR Best Practices And Techniques

ROADSTER 1&2: Clinical Outcomes

FDA Population Analysis

ROADSTER 1 ROADSTER 2

n=219 n=638

Stroke/Death/MI 6 3.7% 10 1.7%

Stroke 1 1.4% 4 0.7%

Death 2 0.9% 1* 0.2%

MI 3 1.4% 5 0.9%

Stroke/Death 3 1.5% 5 0.9%

Neurological Death 0 0.0% 0 0.0%

*One patient expired ~2 weeks post-procedure due to ruptured AAA.

TCD Transfemoral CAS vs CEA vs TCAR

TCAR: avoids the arch, offers complete proximal protection.Similar to CEA.

The PROOF StudyDW-MRI Hits Similar to CEA

Study Procedure Embolic Protection Patients New Ipsilateral DWI Lesions

ICSS2 CEA Clamp, backbleed 107 17%

PROOF3 TCAR Proximal clamp, reversed flow 56 18%

PROFI1 Transfemoral CAS Proximal occlusion (MoMA) 31 45%

ICSS2 Transfemoral CAS Distal filter (various) 51 73%

PROFI4 Transfemoral CAS Distal filter (Emboshield) 31 87%

1. J Vasc Surg 2011;54:1317-232. J Endovasc Ther. 2017 Apr;24(2):265-2703. Lancet Neurol. 2010 Apr;9(4):353-624. J Am Coll Cardiol. 2012 Jan 19. [Epub ahead of print]

76

171

0

20

40

60

80

100

120

140

160

180

Procedure Duration

Transcarotid CASCEA

CEACREST Study

Transcarotid CASROADSTER Study

n=208

Procedure Time M

inut

es

1. ROADSTER Presentation – Late Breaking Trials, VIVA 2014, C. Kwolek, MD2. Stroke. 2012;43:00-00.

ROADSTER vs CREST – Mean Procedure Times (minutes)1,2

10 Minutes

31 Minutes

0

5

10

15

20

25

30

35

Procedure Duration

TranscarotidCAS

CEANASCET Study

n=1,415

Transcarotid CASROADSTER Study

n=208

Reverse Flow Vs. CEA Clamp TimeM

inut

es

1. ROADSTER Presentation – Late Breaking Trials, VIVA 2014, C. Kwolek, MD2. Stroke. 1999;30:1751-1758

ROADSTER vs NASCET 1,2

One-Year Outcomes• Stroke rate: 0.6%• Mortality: 4.2%• 99% stroke free at one year• 95% stroke free survival

TCAR Surveillance Project (TSP)

Objectives of TSP

Monitor the safety and effectiveness of stents placed directly into the carotid artery while reversing blood flow within the carotid artery to reduce stroke risk.

Compare this less-invasive surgical procedure with standard carotid endarterectomy in centers that participate in the Society for Vascular Surgery Vascular Quality Initiative.

Provide “REAL-WORLD” Outcomes

• Inclusion Criteria:Patients undergoing TCAR or CEA who are considered high surgical risk as defined by the CMS criteria

https://clinicaltrials.gov/ct2/show/NCT02850588?term=TCAR+%2C+Surveillance&rank=1

Who is Eligible for TCAR?

Anatomic High-Risk Inclusion Criteria:• Contralateral carotid artery

occlusion• Tandem stenosis >70%• High cervical carotid artery

stenosis• Restenosis after carotid

endarterectomy• Bilateral carotid artery stenosis

requiring treatment• Hostile neck which the

Investigator deems safe for transcarotid access including but not limited to prior neck irradiation, prior radical neck dissection or cervical spine immobility

Clinical High-Risk Inclusion Criteria:

≥ 75 years of age≥ 2-vessel coronary artery disease and history of angina of any severity Unstable angina or Canadian Cardiovascular Society (CCS) angina class 3 or 4 Congestive heart failure (CHF) - New York Heart Association (NYHA) Functional Class III or IVKnown severe left ventricular dysfunction with LVEF <30%.Myocardial infarction > 72 hours and < 6 weeks prior to procedure. Severe pulmonary disease (COPD) with either FEV1 <50% predicted or chronic oxygen therapy or resting PO2 of <= 60 mmHg (on room air) Permanent contralateral cranial nerve injury Chronic renal insufficiency (serum creatinine > 2.5 mg/dL).

CMS High-Risk Criteria criteria

TCAR vs TFCAS

TFCASN = 2430

(%)

TCARN = 2430

(%)

Relative Risk(95% CI)

P-value

Stroke/Death 2.9 1.5 0.52 (0.35-0.77) <.01Stroke 2.3 1.2 0.52 (0.33-0.81) <.01Transient Ischemia Attack 0.9 0.7 0.81 (0.43-1.51) 0.62Death 0.9 0.5 0.57 (0.28-1.16) 0.16Myocardial Infarction 0.5 0.4 0.75 (0.32-1.78) 0.66Heart Failure Exacerbation 0.6 0.5 0.73 (0.34-1.60) 0.56Bleeding Complication 0.3 1.5 4.63 (2.15-9.93) <.001Hemodynamic Instability

Hypotension 18 16 0.84 (0.72-0.97) 0.02Hypertension 15 16 1.13 (0.97-1.32) 0.12

Reperfusion Syndrome 0.5 0.3 0.46 (0.18-1.21) 0.17Technical Failure 1.1 0.5 0.44 (0.23-0.86) 0.02

Unable to access CCA 0.4 0.1 -- 0.02Unable to cross carotid lesion 0.5 0.2 -- 0.11Unable to deploy stent 0.2 0.2 -- 0.99

Procedure time (mins) 74 + 76 75 + 31 -- 0.64Fluoroscopy time (mins) 19 + 16 5.8 + 5.4 -- <.001Contrast Volume (mL) 95 + 58 36 + 23 -- <.001Length of Stay, days, median [IQR] 1 [1,2] 1 [1,2] -- 0.31Failed CMS Discharge Criteria 21 17 0.83 (0.74-0.94) <.01

Prolong Length of Stay 18 14 0.82 (0.72-0.93) <.01Failed Discharge Home 12 7.6 0.65 (0.54-0.77) <.001

Schermerhorn MLS et al. JAMA. October 2019

TCAR vs TFCASUpdated Propensity-Score-Matched Analysis

TCAR vs CEA

Schermerhorn ML, Liang P, Dakour-Aridi H, Kashyap VS, Wang GJ, Nolan BW, Cronenwett JL, Eldrup-Jorgensen J, Malas MB. In-hospital outcomes of transcarotid artery revascularization and carotid endarterectomy in the Society for Vascular Surgery Vascular Quality Initiative. Journal of vascular surgery. 2019 Jun 18.

• 1,182 patients undergoing TCAR vs. 10,797 patients who underwent CEA.• Similar in-hospital stroke/death rates between TCAR and CEA, despite a

substantially higher medical risk in patients undergoing TCAR.• Lower CNI after TCAR vs. CEA

Total Cohort51,986

CEA(n=44,442)

CEA (n=6,135)

TCAR(n=7,544)

TCAR (n=6,135)

After Propensity Score Matching

Initial Cohort

Baseline Characteristics Before Propensity-Score Matching

CEA (N=44,442) TCAR (N=7,544) P-value Mean Standardized

Difference*

Median Age in years (IQR) 71 (65-77) 74 (67-80) <.001 -.28

Female Gender 17,508 (39.4) 2,747 (36.4) <.001 .06Non-White Race 4,513 (10.2) 719 (9.5) . 10 .02Symptomatic Status 13,151 (29.6) 2,942 (39.0) <.001 .20Hypertension 39,766 (89.5) 6,868 (91.1) <.001 .05Diabetes 16,313 (36.7) 2,906 (38.5) <.01 .04CAD 11,874 (26.7) 3,909 (51.8) <.001 .53Prior CABG/PCI 15,316 (34.5) 3,048 (40.4) <.001 .12CHF 4,945 (11.1) 1,353 (17.9) <.001 .19COPD 10,292 (23.2) 2,066 (27.4) <.001 .10CKD 14,597 (33.4) 2,886 (39.1) <.001 .12Dialysis 434 (1.0) 127 (1.7) <.001 .06Smoking <.001 .07

Prior Smoker 21,883 (49.3) 3,936 (52.2)Current Smoker 11,050 (24.9) 1,656 (22.0)

Prior Ipsilateral CEA 758 (1.7) 1,219 (16.2) <.001 .52Prior Ipsilateral CAS 110 (0.25) 110 (1.5) <.001 .13Ipsilateral Stenosis ≥ 80% 20,521 (47.0) 3,895 (53.3) <.001 .13Contralateral CEA/CAS 6,057 (13.6) 1,330 (17.6) <.001 .11Preoperative Medications

Aspirin 37,414 (84.2) 6,733 (89.3) <.001 .15Statins 37,363 (84.1) 6,734 (89.3) <.001 .15P2Y12-Receptor Antagonists 15,712 (35.4) 6,557 (86.9) <.001 1.25Beta Blockers 23,965 (54.0) 4,353 (57.7) <.001 .08Anticoagulation 4,779 (10.8) 4,353 (57.7) <.001 .11ACE Inhibitors 23,623 (53.2) 4,060 (53.9) <.001 .01

Baseline Characteristics after Propensity-Score Matching

CEA (N=6,135) TCAR (N=6,135) P-value

Mean Standardized Difference*

Median Age, IQR 74 (67-80) 74 (67-80) 0.08 0.024Age ≥75 years, n(%) 2,927 (47.7) 2,911 (47.5) 0.68 0.005Female Gender, n (%) 2,189 (35.7) 2,217 (36.1) 0.46 0.010Non-White Race, n (%) 601 (9.8) 614 (10.0) 0.69 0.007Symptomatic Status, n (%) 2,387 (38.9) 2,384 (38.9) 0.94 0.001HTN, n (%) 5,601 (91.3) 5,571 (90.8) 0.35 0.017DM, n (%) 2,401 (39.1) 2,379 (38.8) 0.68 0.007CAD, n (%) 2,999 (48.9) 2,970 (48.4) 0.42 0.009Prior CABG/PCI, n (%) 2,390 (39.0) 2,450 (39.9) 0.11 0.020CHF, n (%) 984 (16.0) 1,062 (17.3) 0.02 0.034COPD, n (%) 1,540 (25.1) 1,654 (27.0) 0.02 0.042CKD, n (%) 2,253 (37.3) 2,312 (38.5) 0.11 0.026Dialysis, n (%) 76 (1.2) 111 (1.8) 0.02 0.049Smoking 0.86 0.007Prior Smoker 3,216 (52.4) 3,194 (52.1)Current Smoker 1,324 (21.6) 1,327 (21.7)Prior Ipsilateral CEA, n (%) 410 (6.7) 465 (7.6) 0.01 0.035Prior Ipsilateral CAS, n (%) 45 (0.7) 63 (1.0) 0.08 0.031Ipsilateral Stenosis >= 80% 3,161 (51.5) 3,165 (51.6) 0.92 0.001Contralateral CEA/CAS 932 (15.2) 960 (15.7) 0.49 0.012Preoperative Medications, n (%)

Aspirin 5,512 (89.9) 5,436 (88.6) 0.004 0.040Statin 5,480 (89.3) 5,471 (89.2) 0.74 0.005

P2Y12-Receptor Antagonists 5,287 (86.2) 5,212 (85.0) <0.001 0.035Beta Blockers 3,510 (57.2) 3,489 (56.9) 0.57 0.007

Anticoagulation 698 (11.4) 826 (13.5) <.001 0.063ACE Inhibitors 3,346 (54.5) 3,284 (53.6) 0.27 0.020

In-Hospital Outcomes after Propensity Score Matching

CEA (N=6,135) TCAR (N=6,135) TCAR vs. CEA

N (%) N (%) Relative Risk (95% CI) P-value

Stroke/Death 94 (1.5) 94 (1.5) 1.0 (0.75-1.33) 1.00Death 25 (0.4) 24 (0.4) 0.96 (0.55-1.68) 0.89Ipsilateral Stroke 57 (0.9) 71 (1.2) 1.25 (0.88-1.76) 0.22Stroke 76 (1.2) 81 (1.3) 1.07 (0.78-1.46) 0.69

MI* 66 (1.1) 28 (0.5) 0.42 (0.27-0.66) <.001

Stroke/Death/MI* 153 (2.5) 116 (1.9) 0.76 (0.60-0.97) 0.03Cranial Nerve Injury 163 (2.7) 10 (0.2) 0.06 (0.03-0.12) <.001Post-procedural Hypotension 665 (10.9) 1,001 (16.4) 1.50 (1.37-1.66) <.001Post-procedural Hypertension 1,294 (21.1) 828 (13.5) 0.64 (0.59-0.70) <.001Bleeding with intervention 104 (1.7) 84 (1.4) 0.81 (0.61-1.08) 0.15LOS more than 1 day 2,250 (36.7) 1,785 (29.1) 0.79 (0.75-0.84) <.001Non-Home Discharge 545 (8.9) 411 (6.7) 0.76 (0.66-0.86) <.001

*Further adjusted for anesthesia choice

CEA (N=3,690) TCAR (N=3,690)In-hospital Outcomes N (%) N (%) Relative Risk (95% CI) P-value Stroke/Death 49 (1.3) 45 (1.2) 0.92 (0.61-1.38) 0.68Death 18 (0.5) 13 (0.4) 0.72 (0.35-1.47) 0.37Ipsilateral Stroke 19 (0.5) 32 (0.9) 1.68 (0.95-2.97) 0.07Stroke 36 (1.0) 36 (1.0) 1.0 (0.63-1.59) 1.00

MI 40 (1.1) 18 (0.5) 0.45 (0.26-0.78) 0.01Stroke/Death/MI 81 (2.2) 58 (1.6) 0.72 (0.51-1.00) 0.05Cranial Nerve Injury 90 (2.4) 5 (0.1) 0.06 (0.02-0.14) <.001Post-procedural Hypotension 367 (10.0) 616 (16.7) 1.68 (1.48-1.92) <.001Post-procedural Hypertension 758 (20.6) 469 (12.7) 0.62 (0.55-0.69) <.001Bleeding with intervention 60 (1.6) 53 (1.4) 0.88 (0.61-1.28) 0.51LOS more than 1 day 1,158 (31.4) 916 (24.8) 0.79 (0.73-0.86) <.001Non-Home Discharge 184 (5.0) 99 (2.7) 0.54 (0.43-0.69) <.001

CEA (N=2,415) TCAR (N=2,415)

N (%) N (%) Relative Risk (95% CI) P-value Stroke/Death 65 (2.7) 51 (2.1) 0.78 (0.54-1.13) 0.20Death 15 (0.6) 11 (0.5) 0.73 (0.34-1.60) 0.44Ipsilateral Stroke 43 (1.8) 40 (1.7) 0.93 (0.60-1.43) 0.74Stroke 54 (2.2) 47 (2.0) 0.87 (0.59-1.29) 0.49

MI 24 (1.0) 10 (0.4) 0.42 (0.20-0.87) 0.02Stroke/Death/MI 85 (3.5) 60 (2.5) 0.71 (0.51-0.98) 0.04

Cranial Nerve Injury 76 (3.2) 3 (0.1) 0.04 (0.01-0.13) <.001Post-procedural Hypotension 301 (12.5) 373 (15.5) 1.25 (1.07-1.45) <.01Post-procedural Hypertension 545 (22.6) 357 (14.9) 0.66 (0.58-0.75) <.001Bleeding with intervention 44 (1.8) 34 (1.4) 0.77 (0.49-1.21) 0.26LOS more than 1 day 1,072 (44.4) 875 (36.2) 0.82 (0.75-0.89) <.001Non-Home Discharge 356 (14.8) 315 (13.1) 0.88 (0.76-1.03) 0.10

30-day Outcomes

30-day follow up (39.1%)

CEA (n=18,020)

CEA (n=1,909)

TCAR (n=2,327)

TCAR (n=1,909)

After Propensity Score Matching

All patients

Thirty-day Outcomes CEA (N=1909) TCAR (N=1,909) TCAR vs. CEA

N (%) N (%) Relative Risk (95% CI) P-valueStroke/Death 48 (2.5) 34 (1.8) 0.71 (0.44-1.14) 0.16Mortality 12 (0.6) 6 (0.3) 0.5 (0.17-1.44) 0.20Ipsilateral Stroke 23 (1.2) 25 (1.3) 1.1 (0.57-2.06) 0.80Stroke 38 (2.0) 31 (1.6) 0.82 (0.49-1.37) 0.44Myocardial infarction 25 (1.3) 11 (0.6) 0.50 (0.26-0.97) 0.04Stroke/Death/MI 72 (3.8) 44 (2.3) 0.63 (0.43-0.92) 0.02

CEA (N=1,190) TCAR (N=1,190)N (%) N (%) Relative Risk (95% CI) P-value

Stroke/Death 5 (0.4) 4 (0.3) 0.80 (0.19-3.44) 0.76Mortality 5 (0.4) 14 (1.2) 2.8 (0.97-8.1) 0.06Ipsilateral Stroke 15 (1.3) 16 (1.3) 1.1 (0.51-2.22) 0.86Stroke 14 (1.2) 6 (0.5) 0.47 (0.19-1.16) 0.10Myocardial infarction 20 (1.7) 17 (1.4) 0.85 (0.42-1.70) 0.65Stroke/Death/MI 32 (2.7) 22 (1.9) 0.69 (0.41-1.17) 0.16

CEA (N=700) TCAR (N=700)N (%) N (%) Relative Risk (95% CI) P-value

Stroke/Death 3 (0.4) 2 (0.3) 0.67 (0.11-3.93) 0.65Mortality 17 (2.4) 11 (1.6) 0.65 (0.29-1.43) 0.28Ipsilateral Stroke 22 (3.1) 16 (2.3) 0.73 (0.38-1.40) 0.34Stroke 8 (1.1) 5 (0.7) 0.63 (0.21-1.89) 0.41Myocardial infarction 24 (3.4) 18 (2.6) 0.75 (0.40-1.39) 0.36Stroke/Death/MI 31 (4.4) 23 (3.3) 0.78 (0.47-1.32) 0.36

Thirty-day Outcomes in the Matched Cohort

One-Year Mortality in the PSM Cohort

CEA vs. TCAR: 95.3% vs. 96.4%HR (95%CI): 0.76 (0.59-0.98), P= 0.04

Conclusions

• Excellent outcomes for CEA, TFCAS and TCAR in TSP VQI• TCAR is safe and effective in patients with multiple anatomic and

physiologic risk factors • Significant reduction in stroke and death after TCAR vs. TFCAS• Patients undergoing TCAR have significant reductions in the odds

of in-hospital MI and cranial nerve injury compared with CEA.• Mortality at 1-year is lower in TCAR versus CEA

Thank you!