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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