ACST-2 Update

Alison Halliday

Professor of Vascular Surgery

University of Oxford

24th January 2017

Disclosure

Speaker name: Professor Alison Halliday

I do not have any potential conflict of interestx

Systematic review, de Weerd, 2009

Adults over 70 years:

≥70% stenosis ~ 3% women

5% men

≥50% 7% women

12% men

Prevalence of ‘serious’ carotid stenosis

Annual Stroke risk from asymptomatic carotid stenosis

= randomised trial (60-99%) = cohort/non RCT (50%+)

Marquardt et al. Stroke 2010

Asymptomatic carotid stenosis:

Even on anti-thrombotic, blood pressure lowering and lipid-lowering

(triple) medical therapy -

successful CEA halves the stroke rate over the next 5-10 years.

VACS ACAS ACST-1

Nos. of patients(Immediate vs Deferred)

444(211 vs 233)

1662(828 vs 834)

3120(1560 vs 1560)

Period of randomisation Apr 83 – Oct 87 Dec 87 – Dec 93 Apr 93 – Jul 03

Date of last follow-up May 1991 Feb 1997 May 2008

Median (IQR) follow-up year 4.5 (2.5-6.0) 4.2 (2.9-5.0) 6.1 (3.9-9.1)

Carotid Endarterectomy (CEA) to prevent stroke Open surgery vs Medical treatments

5,000 individual patients in ACST-1, ACAS and VACS Trials

if CT/MR archimaging shows

patient is suitable forboth procedures

-then randomise

-but….CAS was

previously more hazardous than CEA

Now ACST-2 directly compares CEA vs CAS

Two main hazards – crossing the lesion and navigating in the aortic arch

CEA – open removal of atheroma under direct control

Can CAS be as safe – but much less invasive?

Our PatientsSex, Age, Co-morbidities:Men 70%Age (range 42-92) - median 69 yearsIschaemic heart disease 37%Diabetic 30%Renal impairment 8%

Stroke risk factors:Atrial Fibrillation 6%Age >75 yrs 26%Previous stroke symptoms or infarct 40%

Blood pressure:≥160mm Hg systolic 8%>90 mmHg diastolic 7%

Our PatientsIpsilateral Stenosis:Median 80%50-69% 4%70-89% 73%90-99% 23%

Contralateral Stenosis:50-99% 30%Occlusion 7%

Definite Plaque Echolucency: 29%

Cholesterol:Total (Mean) 4.7mm/l (ACST-1 5.6)HDL 1.3mm/l

Time from randomisation until procedure

CEA: 24 days

CAS: 27 days

80% lipid-lowering

85% anti-hypertensive

95% anti-thrombotic (anti-platelet +/or anti-coagulant)

Drugs at Trial Entry

Drug therapy at 1 month

Total allocated

procedures done

(n=2210)

Anti-hypertensive 84%

Lipid-Lowering 85%

Anti-platelet or

anti-coagulant97%

On at least one of

aspirin or clopidogrel93%

On both

aspirin and clopidogrel39%

Mean follow-up in January 2017

CEA: 2.9 person-years

CAS: 2.9 person-years

Drugs at 2015 follow-up

CAS

(n=676)

CEA

(n=687)

Total allocated

procedure done

(n=1363)

Anti-hypertensive 83%

Lipid-Lowering 82%

Anti-platelet or anti-

coagulant93%

On at least one of

aspirin or clopidogrel86%

On both

aspirin and clopidogrel13% 7% 10%

Atorvastatin 51%

Simvastatin 28%

Rosuvastatin 17%

Other statins 4%

Fibrates 2%

Ezetimibe 7%

On 2 lipid-lowering drugs 12%

Annual Follow up 2016

Lipid Lowering Treatment

Compliance with allocated treatment (2015)

Allocated

procedure

1-month form

entered

Procedure

not yet doneCross-over

Procedure as

allocated

CAS 41

CEA 29

Total 100% 5% 4% 91%

Use of Anaesthetic /Patches

PATCHESGeneral anaesthetic

Local anaesthetic

53% 30%

Use of Anaesthetic /Shunts in 1074 CEAs

SHUNTSGeneral anaesthetic

Local anaesthetic

29% 8%

Flow-reversalProtection device

Stent and Device changes since earlier trials

Stent and Device changes since earlier trials

MembranecoveredStent

Stent and Device changes since earlier trials

And now: the ‘surgical’ approach to stenting – avoiding aortic arch atheroma, controlling flow reversal

Stent type Name % used

Closed Stents

Wallstent

Xact 43%

Adapt

Precise

Open

RX Acculink

Protégé® RX 34%

ViVEXX

Zilver

Hybrid

Cristallo Ideale

Sinus Carotid RX 18%

Medtronic Invatec

MER

Membrane Roadsaver 3%

CGuard 2%

Total n = 1020

2008 2009 2010 2011 2012 2013 2014 2015 2016

Stent Devices by YearF

req

uen

cy (

%)

Year

0

20

40

60

80

100

Membrane

Hybrid

Closed Cell

Open Cell

Type of Cerebral

Protection DeviceDevice Name % of total

Filter

Emboshield

Filterwire

Spider

Accunet 67%

AngioGuard

FiberNet

Wirion System

Proximal occlusionMoma 18%

Gore Flow Reversal

Distal balloonTwin One <1%

Viatrac

None 15%

Total 1020

2008 2009 2010 2011 2012 2013 2014 2015 2016

Cerebral Protection by YearF

req

uen

cy (

%)

Year

0

20

40

60

80

100

None

(Distal Balloon)

Proximal Occlusion

Filter

ACST-2 procedural hazards

much lower than in previous trials

Disabling and fatal Stroke/MI ≤ 30 days for CEA/CAS:

1.0% (ACST-2)

Lower than in previous trial of CEA

1.7% (ACST-1)

Trials in asymptomatic stenosis

CAS v CEACREST 1 1182 (too small)ACT-1 1450 (too small)ACST-2 2400/3600 recruiting to 2019

Medical Treatment vs InterventionSPACE 2 513, stoppedECST-2 150, pilot, plan 2000 (most symp) CREST 2 467/2480

Total CAS vs CEA 6230 patients ACST-2 can provide up to 60% of this

….And much of the long term evidence

5032

1130

0 100 200 300 400 500 600

Other countries

Slovenia

Spain

Switzerland

France

The Netherlands

Greece

Poland

Hungary

Czech Republic

Belgium

Russia

Germany

Sweden

Serbia

United Kingdom

Italy

Italy – Best recruiters in ACST-2

but every patient counts!

Recruitment – on our WebsiteOctober 2016 September 2016

East Tallinn Central Hospital 2Novosibirsk Research Institute 3Klinikum rechts der Isar Muenchen 2Semmelweis Medical University 2Albert Szent-Györgyi Medical Centre 1Cheltenham General Hospital 1Circolo University Hospital 1Dedinje Cardiovascular Unit 1Foothills Medical Centre 1Guadalajara Hospital 1Kent and Canterbury Hospital 1Lasarettet Helsingborg 1Malmo Vascular Centre 1Mirano Hospital 1Nottingham University Hospital 1San Giovanni Di Dio 1Santa Maria Hospital 1Serbian Clinical Centre 1Sodersjukhuset 1St. Anna University Hospital Ferrara 1Teaching Hospital Maribor 1University of Basel 1TOTAL SEPTEMBER 27

Novosibirsk Research Institute of Circulation Pathology 4Serbian Clinical Centre 3University of Bologna 3UniversitäTsklinikum Leipzig 3Santa Maria Hospital 2Sodersjukhuset 2University of Dresden 'Carl-Gustav-Carus' 2Cantonal Hospital Aarau 1Cefalù Fondazione Istituto G. Giglio 1Ceske Budejovice - Budweiss 1Dedinje Cardiovascular Unit 1Hospital de Santa Marta 1Istituto Auxologico Italiano 1Mirano Hospital 1Semmelweis Medical University 1Sendai Medical Centre 1St Anne's University Hospital Brno

1UniversitäTs Klinikum Hamburg-Eppendorf 1Vascular Endovascular Unit of Perugia 1Wythenshawe Hospital (University of South Manchester) 1

TOTAL OCTOBER 32

Website Front Page:

Our new patient (s) were

randomised from:

ACST-2 target –3600 patients

0

600

1200

1800

2400

3000

3600

2010Jan

2011Jan

2012Jan

2013Jan

2014Jan

2015Jan

2016Jan

2017Jan

2018Jan

2019Jan

2020Jan

Projectedrecruitment

Currentrecruitment

2400 recruitedalready

ACST-2 Update

Two-thirds randomised-1200 more needed

to complete recruitment by end 2019

ACST-2

European

33 countries

Large Network:

Neurologists

Surgeons

Cardiologists

Radiologists

You are welcome

to join us:

www.acst-2.org

ACST-2 Update

Alison Halliday

Professor of Vascular Surgery

University of Oxford

24th January 2017