Interventional Approach to Carotid Artery Disease The New Paradigm

VIVA 2008 ( Las Vegas, NV)September 22nd 2008

1 AP2928021 Rev A

Carotid stenting is not currently approved by the FDA for asymptomatic patients who are at standard risk for surgery.CAUTION: Investigational device. Limited by Federal (or United States) law to investigational use.Confidential: This information is confidential and is intended for distribution to ACT I Study Site participants ONLY. This document contains Abbott Laboratories and Abbott Vascular proprietary information and shall not be duplicated, disclosed to others, or used for purposes other than to carry out the intent for which this material is delivered.©2008

Asymptomatic Carotid stenosis, stenting versus endarterectomy Trial

Update on ACT IAlex Abou-Chebl, MD

SymptomaticHigh-risk

Symptomatic

Standard-risk

Asymptomatic

Standard-risk

Asymptomatic

High-risk

Asymptomatic Carotid Artery Disease RCT’s: CAS vs. CEA

CRESTACT 1, SPACE 2

ongoing

VIVA 2007 ( Las Vegas, NV)September 25th 2007

ACT I: Study Design

•Prospective, randomized, 2-arm, multicenter trial

•3:1 randomization CAS to CEA

•Lead-in enrollment of up to 400 subjects

•Maximum of 1658 pivotal subjects

•Followed at 1, 6, 12 months & annually for 5 yrs

•Contemporary medical therapy for all patients

4

ACT I: Primary Endpoint

• Composite of Death, Stroke, MI at 30 days post procedure

PLUS

• Ipsilateral Stroke from 31 to 365

days post procedure

5

ACT I: Secondary Endpoints• Death (years 2-5)

• Ipsilateral stroke (years 2-5)

• Composite Morbidity Measure: Cranial nerve injury, bleeding, vascular and/or wound complications requiring treatment, complications of general anesthesia, access artery, renal and airway complications

• Freedom from clinically-indicated target lesion revascularization (TLR) at 6 and 12 months

• Acute stent success: Residual stenosis < 50% by QCA covering an area no longer than original lesion

• Acute filter success: Successful deployment and retrieval of filter in absence of angiographic distal embolization.

• Procedure success: Residual stenosis < 50% by QCA and freedom from Major Adverse Event at 30 days


ACT 1 (vs. CREST)Patients

• Asymptomatic only– powered to look at them independently

• Lesion criteria– Stenosis > 70%

– DUS velocities higher

• NO Octogenarians

• Emphasis on case selection…avoidance of patients not

good for both therapies

• Encouragement to cross over if CAS/CEA not appropriate

(more about the patient than proving the therapy)


ACT 1 (vs. CREST)Investigators

• SMC and IMC highly “selective”– Actual case angio reviews (IMC)

• Later in experience curve of stenting– Optimal case selection

– Operator experience more comparable to surgeons doing CEA

• Ongoing review of outcomes: Trigger for MAE that are

well beyond expected event rates• Enrollment expectations…Probation and termination of

non-enrolling sites/investigators• Fewer # study sites, all high-quality

The influence of experience

* Hierarchical Events – Includes only the most serious event for each patient and includes only each patient’s first occurrence of each event.

All stroke/death*

Level I CAPTURE: n= 210

EXACT: n= 267 CAPTURE 2: n=83

Level 2 CAPTURE: n= 1879 EXACT: n=776 CAPTURE 2: n=1026

Level 3 CAPTURE: n=735

EXACT: n=482 CAPTURE 2: n=318

Asymptomatic patients <80 years

2.5%

3.4%3.8%

0%

1%

2%

3%

4%

5%

6%

7%

8%

Str

oke

Dea

th r

ates

Avoiding the Eva3S debacle!


ACT 1 (vs. CREST)Devices

•Devices: – Xact stent (closed cell) with Emboshield/Embo-pro

Vs

– Acculink (open cell) with Accunet

Carotid Stents - open vs closed cell?Stent cell area

Houdart E, CIRSE 2006

closed closed open open open closed openStentDesign:

Cell area (mm2)

Tortuous ICA: • 90 degree take-off• 120 degree prox.

turn

Excessive TortuosityHeavy concentric Ca++

Excluded from ACT I


ACT 1 vs. CRESTConduct of trial- adjuvant therapy

•Emphasis on Optimal Medical Therapy– Mandatory monitoring of Hgb-A1C, cholesterol, etc.


ACT 1 vs. CREST

• Industry sponsored and monitored

vs.

•NIH Trial


ACT 1 Reasons to pursue and complete

• Need for accrual of as much “clean” data as possible– To achieve scientific goals– To validate or invalidate the therapy as viable option for

patients for the future• CREST not comparable• No similar trial is likely to happen in the future• ACT I is unmatched in its scientific rigor and sets the

standard for CAS trials• Determine merits of CAS vs. CEA on scientific, evidence-

based grounds (not political or economic)

15

Enrollment Update

As of 13 Jan 2010:– Total Randomized Subjects: 980– Total number of lead-ins to date: 176– Total number of sites initiated: 53


William Beaumont Hospital

St. John’s Hospital / Prairie Medical Millard Fillmore Hospital

Lenox Hill Hospital

Riverside Methodist Hospital

St. Mary’s Hospital/ VA Cardiovascular Specialists

Duke University

El Camino Hospital Washington Hospital Center Northwestern University Memorial Hospital

Berks Cardiology

Harrisburg Hospital / Pinnacle Health

Cleveland Clinic Foundation

Hoag Memorial Hospital Presbyterian

Presbyterian Heart Institute-Dallas

Oregon Health & Science University

Parkview Hospital

North Central Heart Institute Detroit Medical Center

Baptist Hospital of East Tennessee

BCVI

Forsyth Medical Center

Ochsner Clinic Foundation

Massachusetts General Hospital

Deaconess Medical Center

St. Joseph Hospital Wellness Center

Albany Medical Center

St. Luke’s Episcopal Hospital, Houston

Columbia Presbyterian

Rush University Medical Center

Cardiovascular Inst. of the South

Austin Heart P.A.

Wake Medical Center

Kaiser Foundation Hospital – San Diego

NYU Medical Center

St. Luke’s Hospital, Phoenix

Westlake Medical Center

Dartmouth Enrolling Sites as of September 2009

Kaiser Permanente Hawaii

University of Rochester

St. Francis, NY

Providence Medical Center

Our Lady of Lourdes

Allegheny General Hospital

Chesapeake General Hospital

Hospital of Univ. of Pennsylvania

St. Luke’s Milwaukee

Stern Cardiovascular Center

Wellmont Holston Valley

St. John’s Mercy

Heritage Valley


ACT I: Primary Endpoint

•Composite of Death, Stroke, MI at 30 days post procedure

PLUS

• Ipsilateral Stroke from 31 to 365 days post procedure


Independent Clinical Events Committee (CEC)

•Reviews and adjudicates the following events:– Cause of Death through 30 days (Attempt to determine if neurological,

cardiac, other)– Suspected Stroke (All through 30 days, Ipsilateral between 31 days and 365

days (post-procedure)– Suspected MI (All suspected Q wave and non-Q wave through 30 days of

procedure)


Analysis Cohort

•Patient cohort analyzed:

ACT I Lead In, n=160 as of June 30, 2009

•Analysis cohort includes:– patients with 30 day follow-up visits or

event(s) within 30 days (n=160).– Patients with 1 year follow-up visits or

event(s) within 1 year (n=146).


Procedural and Device Success

• Procedural Success- 98.1% (157/160)

• Acute Xact Success- 97.5% (159/163)

• Emboshield Success- 99.4% (160/161)


ACT I: Outcomes Lead In Patients

Event 30 days, N=160

Death, Stroke and MI 1.3% (2/160)

All Stroke and Death 1.3%

Major Stroke and Death 0.0%

Death 0.0%

All Stroke 1.3%

Major Stroke 0.0%

Minor Stroke 1.3%

MI 0.0%

31-365 days, N=146

Ipsilateral Stroke 0.0%

CREST Lead-In Phase

•Up to 20 patients per interventionist•Non-randomized N =1246

– Low and High-CEA risk– 65% Asymptomatic

•30-Day Stroke/Death – Asymptomatic 3.1%– Symptomatic 4.3%– Combined 3.9%– Age>80 12.1%


Summary

•ACT I is a randomized trial comparing patients at standard risk for CEA and CAS

•Lead-in data suggests CAS event rates comparable to CEA

•Results from ACT I will, more than any trial to date, determine the role of CAS

•Patients, physicians, CMS, other payers will make therapeutic decisions based on results of ACT I

Poor Stent Candidates

Documents

Interventional Approach to Carotid Artery Disease The New Paradigm