ACST-2 over 2500 patients randomised, what do we know? · Cefalù Fondazione Istituto G. Giglio 1...

ACST-2 –over 2500 patients randomised, what do we know?

Alison Halliday, Professor of Vascular SurgeryUniversity of Oxford30th January 2018

Disclosure

Speaker name: Alison Halliday

I do not have any potential conflict of interest

Asymptomatic stenosis – what is important?

• Stroke, not just ipsilateral stroke

• Durability of any treatment – 5-10 years at least

• Affordability – drugs for ever, intervention once

• Appropriate patients - high-risk vs any patient

ACST-2:A very European Trial in

Over 30 countries

Large Network: Neurologists,

Surgeons, Interventionalists

ACST-2 Surgery vs Stenting

Asymptomatic patients with tight stenosis requiring intervention:

Which procedure is generally better (in addition to good medical treatment)? :

carotid surgery (CEA)or

carotid stenting (CAS)?

ACST-2 – what makes it different from other trials?

Collaborators are free to use their usual techniques

Any CE marked stent. CPD not mandatedGA or LA; Primary or patch closure…

Two stenting hazards – crossing the

lesion + navigating in the aortic arch

Asymptomatic carotid disease –modern CAS therapy since ACT-1

Stable plaque - lower peri-procedural risk and..

• Newer stent designs

• Flow reversal (MOMA)

• Direct cervical access (TECAR)

• Greater experience

May

reduce

risk

further

Carotid Stents – Avoid plaque protrusion

Closed Cell

Open Cell

Membrane covered

And: the direct approach to stenting – avoiding

aortic arch atheroma, controlling flow reversal

ACST-2: What do we know?Sex, Age, Co-morbidities:

Men 70%

Median age 69 years

Ischaemic heart disease 37%

Diabetic 29%

Renal impairment 9%

Stroke risk factors:

Atrial Fibrillation 6%

Age >75 yrs 26%

Previous stroke symptoms or infarct 35%

ACST-2: What do we know?Ipsilateral Stenosis:Median 80%50-69% 3%70-89% 73%90-99% 23%

Contralateral Stenosis:50-99% 31%Occlusion 7%

Plaque Echolucency: 29%

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

Time from randomisation to procedure

Jan 2018

CEA: 24 days

CAS: 29 days

Compliance with allocated

treatment

Allocated

procedure

1-month form

entered

Procedure

not yet doneCross-over

Procedure as

allocated

CAS 62

CEA 39

Total 100% 4% 4% 91%

Mean follow-up January 2018

CEA: 3.6 person-years

CAS: 3.6 person-years

Surgery: anaesthesia and techniques

(3% CAS under GA)

General714 (58%)

Local515 (42%)

Total1231

Patches Yes

377 (53%) 150 (29%) 527 (43%)

Shunts Yes

207 (29%) 39 (8%) 246 (20%)

2017 ESVS and ESC Guidelines

81% lipid-lowering drugs

85% anti-hypertensive therapy

96% anti-thrombotic(anti-platelet/anti-coagulant)

ACST-2 ‘modern’ medical therapy

- At Trial Entry

and long-term compliance is good

1 month after treatment

Allocated procedures

(n=2391)

Anti-hypertensive 86%

Lipid-Lowering 88%

Anti-platelet or

anti-coagulant99%

On at least one of

aspirin or clopidogrel96%

On both

aspirin and clopidogrel41%

2016 Annual follow-up

CAS

(n=793)

CEA

(n=818)

Total allocated

procedure done

(n=1650)

Anti-hypertensive 80%

Lipid-Lowering 80%

Anti-platelet or anti-

coagulant93%

On at least one of

aspirin or clopidogrel85%

On both

aspirin and clopidogrel12% 8% 10%

Atorvastatin 42%

Simvastatin 23%

Rosuvastatin 13%

Other statins 4%

Fibrates 1%

Ezetimibe 5%

On 2 lipid-lowering drugs 5%

2016 Annual Follow up

Lipid Lowering Treatment

2009 2010 2011 2012 2013 2014 2015 2016

Statin Use by YearF

req

uen

cy (

%)

Year

0

20

40

60

80

100

Long-term statin use >80%

2013 2014 2015 2016

Intensity of Statin Therapy by YearF

req

uen

cy (

%)

Year

0

20

40

60

80

100 (Unclear)

High Dose

Moderate Dose

Low Dose

>75% on good (or very good)

statin regimens

Simva 40 Atorva 20 Rosuva 10 Combined

Wallstent (Closed) (44%) 306

Xact 188

Adapt 10

Precise (Open) (34%) 155

Protégé® RX 113

RX Acculink 111

ViVEXX 9

Zilver 7

Cristallo Ideale (Hybrid) (16%) 175

Sinus Carotid Conical RX 10

Mer 1

Roadsaver (Membrane) (6%)

CGuard

46

26

TOTAL 1160

Stents used

Filter (67%) Emboshield 252

Filterwire 231

Spider 170

Accunet 74

AngioGuard 47

FiberNet 1

Wirion System 1

Proximal

occlusion (17%)

Moma

Gore Flow Reversal

171

29

Distal balloon Twin One

Viatrac

6

2

None (15%) 177

1160

CPD use

ACST-2 and modern CAS therapy

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

Cerebral Protection in

~85% of cases

2008 2009 2010 2011 2012 2013 2014 2015 2016

Stent Devices by Year

Fre

qu

en

cy (

%)

Year

0

20

40

60

80

100

Membrane

Hybrid

Closed Cell

Open Cell

Closed cell stents predominateMembrane stents emerging

ACST-2 stenting

• Medical therapy in ACST-2 is good (>80%)Moderate and high statin regimens favoured

• Cerebral protection widely used (85%)

• Flow reversal quite common (17%)Mo.Ma often used

• Closed cell stents still predominate (43%)Membrane-mesh covered stents emerging

ACST-2 Procedural hazards (CEA+CAS)much lower than symptomatic trials

Disabling and fatal Stroke ≤ 30 days :

1.0%

Suggests procedural competence in ACST-2,

confirms interventions are low-risk

And lower than in previous trial

of CEA :

1.7% (ACST-1)

Recruitment - target 3600

0

600

1200

1800

2400

3000

3600

2010Jan

2011Jan

2012Jan

2013Jan

2014Jan

2015Jan

2016Jan

2017Jan

2018Jan

2019Jan

2020Jan

Projectedrecruitment

Currentrecruitment

2778

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 (>650)(UK >400)

Recruitment – Website (acst-2.org)October 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 4

Serbian Clinical Centre 3

University of Bologna 3

UniversitäTsklinikum Leipzig 3

Santa Maria Hospital 2

Sodersjukhuset 2

University of Dresden 'Carl-Gustav-Carus' 2

Cantonal Hospital Aarau 1

Cefalù Fondazione Istituto G. Giglio 1

Ceske Budejovice - Budweiss 1

Dedinje Cardiovascular Unit 1

Hospital de Santa Marta 1

Istituto Auxologico Italiano

1

Mirano Hospital 1

Semmelweis Medical University

1

Sendai Medical Centre 1

St Anne's University Hospital Brno

1

UniversitäTs Klinikum Hamburg-Eppendorf 1

Vascular Endovascular Unit of Perugia

1

Wythenshawe Hospital (University of South Manchester)

1

TOTAL OCTOBER

32Website Front Page:

Our new patient (s) were

randomised from:

ACST-2 Time Line

Jan 2018 Nearly 2800 randomised

Dec 2019 Randomise 800 more patients

Median follow-up of 5 years

Mid 2021 ACST-2 report 5-year results

Procedural risks and early benefits

IPD: with CREST-1, ACT-1 + SPACE-2 (n=6000)

Mid 2025 ACST-2 10-year results

Reliably compare durability of CEA vs CAS

ACST-2 –over 1500 patients randomised, what do we know?

Alison Halliday, Professor of Vascular SurgeryUniversity of Oxford30th January 2018