UPDATE ON THE NORTH AMERICAN RCTs – CREST 2 & ACST 1: WILL CAS SURVIVE AS AN ALTERNATIVE TO BMT OR CEA ?

FRANK J. VEITH

MAC - 2016 MUNICH – DECEMBER 1, 2016

6TH MUNICH VASCULAR CONF

I HAVE NO FINANCIAL CONFLICTS ALTHOUGH – LIKE ALL OF YOU - I HAVE LOTS OF BIASES

I AM NOT GOING TO TELL YOU ANYTHING ABOUT ACST 1 BECAUSE IT IS MOSTLY NOT NA & ALISON HALLIDAY WILL TELL YOU ALL ABOUT ACST 1

CREST 2 • NOT GOING TO SAY MUCH NO RESULTS – FUNDED BY NIH & RECRUITING

• RCT OF Rxs FOR ACS PTS IN 2 PARTS:

1. CAS & BMT vs BMT 2. CEA & BMT vs BMT

CREST 2 • MAY OR MAY NOT BE HELPFUL TO CAS SINCE ACS PTS IN CREST 2 MAY NOT BE AT HIGH ENOUGH RISK OF STROKE TO SHOW BENEFIT FOR CAS & MAY BE OUT OF DATE – WILL HAVE VALUE - SEE WHY LATER IN TALK

DESPITE LEVEL 1 & OTHER NEW EVIDENCE TO THE CONTRARY THE OUTLOOK FOR AN UPSURGE IN CAROTID STENTING (CAS) IS BRIGHT

SO I AM GOING TO SPEND THE REST REST OF MY TIME TELLING WHY

DESPITE SOME OPINIONS TO THE CONTRARY CAROTID STENTING OR CAS IS CURRENTLY IN DECLINE GENERALLY FOR TREATMENT OF SYMP & ASYMPTOMATIC CAR STENOSIS THIS IS BECAUSE…

WITH

SYMPTOMATIC

CAROTID STENOSIS PTS RECENT RCTs*, POPULTION BASED

STUDIES & A SYSTEMATIC REGISTRY

REVIEW^ (2015) SHOWED MUCH

HIGHER STROKE/DEATH RATES WITH

CAS THAN CEA

*CREST, ICSS, ETC

^Paraskevas, Naylor: EJVES 2015

& WITH MOST

ASYMPTOMATIC

CAROTID STENOSIS

PATIENTS

BEST MEDICAL TREATMENT

HAS SUCH LOW STROKE RATES

THAT IT MAY MAKE

CAS (& CEA) UNNECESSARY

ANNUAL STROKE RATE WITH ASX CS

DECREASED DUE TO BETTER BMRx

& STATINS FROM 3-6% TO <1% / YR

< 1% PER YR IN 2016

3-6% PER YR IN 1985

FROM A ABBOTT & R NAYLOR

IMPORTANT NEW

EVIDENCE !

ONE ARTICLE BY SPENCE*

CONFIRMS THE LOW RISK OF

OCCLUSION (<0.1%) & STROKE (.9%)

IN PATIENTS WITH ASx CAR STEN

ON GOOD MEDICAL Rx

*BY YANG, SPENCE ET AL

JAMA NEUROL, SEPT 21, 2015

A SECOND RECENT ARTICLE BY

PARASKEVAS, NAYLOR (EJVES 2015)

WAS A SYSTEMATIC REVIEW OF

STROKE & DEATH RATES AFTER

CAS & CEA IN 21 CONTEMPORARY

ADMINISTRATIVE REGISTRIES

IT SHOWED THAT

CAS HAD SIGNIFICANTLY HIGHER

STROKE/DEATH RATES THAN CEA

IN MOST OF THESE REGISTRIES FOR

SX & ASX CS

IN MANY CASES EXCEEDING AHA GLs

AHA GUIDELINES FOR

STROKE/DEATH RATES

FOR INVASIVE Rx OF ACS

<3%

FOR INVASIVE Rx OF SX CS

<6%

HERE ARE SOME SPECIFICS*

CAS STROKE/DEATH RATE FOR

AVERAGE RISK Sx CS EXCEEDED

AHA GUIDELINE OF 6% IN 72%

OF 18 REGISTRIES &

IN 28% IT EXCEEDED 10% !!!

*PARASKEVAS, NAYLOR: EJVES 2015

SO CAROTID STENTING OR CAS IS CURRENTLY IN DECLINE GENERALLY FOR TREATMENT OF SYMP & ASYMPTOMATIC CAR STENOSIS

HOWEVER

HOWEVER, I BELIEVE OUTLOOK FOR CAS IS BRIGHT BECAUSE 3 ADVANCES MAY DECR STROKES

• BETTER EMBOL PROTECT DEVICES WITH CESS/REVERSAL OF FLOW (MOMA)

• CERVICAL ACCESS (SILK ROAD SYSTEM) TO AVOID THE AORTIC ARCH & REV FL • MEMBRANE OR MESH COVERED STENTS TO STOP DELAYED STROKES

OUR 1995 EX VIVO MODEL OF CAS

LET US LOOK AT THESE 3 ADVANCES THAT MAY DECR STROKES WITH CAS

2. BETTER EMBOL PROTECT DEVICES WITH CESS/REVERSAL OF FLOW 3. CERVICAL ACCESS (SILK ROAD SYSTEM) TO AVOID THE AORTIC ARCH & REV FL 1. MEMBRANE OR MESH COVERED STENTS TO STOP DELAYED STROKES

DEBRIS THOUGH STENT

CAUSING DELAYED EMBOLI

THE SOLUTION MEMBRANE OR MESH

COVERED STENTS

TERUMO

A MESH COVERED STENT TO PREVENT

DELAYED EMBOLIZATION

ROADSAVER

TRIALS PROMISING

BUT NEED MORE

MORE & LATE

RESULTS TO BE SURE

THEY DON’T INCREASE

LATE STENOSIS

OTHER 2 ADVANCES THAT MAY DECR STROKES WITH CAS

2. BETTER EMBOL PROTECT DEVICES WITH CESS/REVERSAL OF FLOW (MOMA)

3* CERVICAL ACCESS (SILK ROAD SYSTEM) TO AVOID THE AORTIC ARCH & REV FL 1. MEMBRANE OR MESH COVERED STENTS TO STOP DELAYED STROKES

A NEW, SURGICALLY-INSPIRED

ENDOVASCULAR SOLUTION

CAUTION: Investigational device. Limited by federal (USA) law to investigational use.

The ENROUTE™ Transcarotid Stent and Neuroprotection Systems bear the CE mark of conformity and are

available for sale in EU and EFTA countries.

Blood flow is reversed

from the common

carotid artery

Dynamic Flow

Controller

Hi / Low / Off Embolic

filter (200µ)

Blood flow is returned

to femoral vein

Shorter delivery system

and wires for simplified

setup and delivery

ENROUTE™ Transcarotid Stent and Neuroprotection System

EARLY RESULTS IN 3

TRIALS* IN HIGH RISK PTS

ARE PROMISING

BUT WE NEED MORE &

LONGER TERM RESULTS

*PROOF, TESLA, ROADSTER

SO

CAS WOULD BE MORE

COMPETITIVE TO CEA

& WOULD REPLACE CEA

MORE WIDELY

THAN IT DOES NOW

FOR SYMPTOMATIC & ASX PTS

- IF THESE 3 ADVANCES

DECREASE CAS STROKE RATES

1. TCD DETECTED MICROEMBOLI

2. DUPLEX PLAQUE EVALUATION

3. MRI & CT PLAQUE EVALUATION

4. SILENT MRI & CT INFARCTS SOME ASX PT GROUPS HAVE >12%

PER YEAR STROKE RISK vs <1%

FOR ASYMPTOMATIC PATIENTS

THERE ARE PROMISING WAYS

ON THE HORIZON TO SELECT

THOSE AT HIGH RISK OF STROKE

THESE HIGH RISK

ASYMPTOMATIC PTS SELECTED

BY THESE METHODS CLEARLY

WOULD BENEFIT MORE FROM

CAS OR CEA - IN ADDITION TO

BEST MEDICAL TREATMENT

THUS INCREASING THE NUMBER

OF PATIENT NEEDING CAS

HOWEVER THERE IS 1 RESERVATION:

THAT IS

THE EFFICACY OF THESE 3 METHODS

FOR DECREASING CAS STROKE

RATES & IMPROVING ASX PATIENT

SELECTION MUST BE PROVEN

BY APPROPRIATE TRIALS

MY CONCLUSIONS

1. DESPITE THIS RESERVATION

I BELIEVE THE OUTLOOK FOR

CAROTID STENTING OR CAS

IS BRIGHT IN THE FUTURE

2. ALL VASCULAR SPECIALISTS

SHOULD PREPARE FOR

IMPROVING CAS RESULTS

THANKS FOR YOUR ATTENTION

SURGICAL OUTCOMES IN STROKE REDUCTION

Silk Road Clinical Studies

PROOF TESLA ROADSTER

Study type First In Man Multicenter EU Post-

Market Registry US Pivotal IDE

Number of Patients

75 58 141

Profile All-comers All-comers High Surgical Risk

Status Complete Complete Enrollment Complete

VAST 3 2014

PROOF Study: Micro-Embolic Measurements

Manish Mehta MD, EVS 2015

• DW-MRI Studies – TCAR’s CEA like Outcomes

Study Procedure Embolic

Protection

Patie

nts

% w/ New

DWI Lesions

ICSS2 CEA Clamp,

backbleed 107 17%

PROOF3 Silk Road

Transcarotid Access, Flow

Reversal 56 19%

PROFI1 Transfemoral

CAS

Proximal occlusion (MoMA)

31 45%

ICSS2 Transfemoral

CAS

Distal filter

(various) 51 73%

PROFI1 Transfemoral CAS

Distal filter (Emboshield)

31 87% 1 J Am Coll Cardiol. 2012 Jan 19. [Epub ahead of print]

2 Lancet Neurol. 2010 Apr;9(4):353-62

VAST 3 2014

ROADSTER Study – Subgroup Analysis

High Surgical Risk

Pivotal Intention to

Treat

Age ≥ 75 Symptomatic

N N=66 (47%) N=36 (26%)

S/D/MI 3 (4.5%) 1 (2.8%)

Major Stroke 0% 0%

Minor Stroke 0% 0%

Death 3.0% 2.8%

MI 1.5% 0%

Stroke & Death 3.0% 2.8%

ONE ARTICLE CONFIRMS THE

LOW RISK OF OCCLUSION (<0.1%)

& STROKE (.9%)

IN PATIENTS WITH ASx CAR STEN

ON GOOD MEDICAL Rx

THIS IS IN A NEW ARTICLE

BY YANG, SPENCE ET AL

JAMA NEUROL, SEPT 21, 2015

& RISK OF STROKE WITH OCCL = 0.32%

SILK ROAD CERVICAL

ACCESS SYSTEM WITH

REVERSAL OF FLOW