Safer Trials, Safer stenting Time to change your practice?

Transcription

1 Safer Trials, Safer stenting Time to change your practice? Alison Halliday Professor of Vascular Surgery University of Oxford UK Stroke Forum Parallel Session 2B Carotid Stenosis Tuesday 29 th November 2016 NB. This is an edited version, as some of the data presented has not yet been published The conclusions are, however, unchanged

2 About 20% ischaemic Strokes are caused by carotid stenosis

3 Performance of CEA around Europe In the UK, CEA is less frequently performed when compared with a number of other European nations. ( ) CEAs/100,000 population/yr UK 5.1 Denmark 7 Sweden 12.4 Germany 31.7

4 Prevalence of serious carotid stenosis Systematic review, de Weerd, 2009 >50% = 4.2% >70% = 1.7% Adults over 70 years: >50% = 7% women 12% men

5 40 years of carotid surgery trials Carotid endarterectomy [CEA] vs not s: symptomatic patients s: asymptomatic patients CEA vs carotid stenting s: symptomatic patients -2010s: asymptomatic patients

6 Asymptomatic Carotid Disease Medical Management or Revascularisation?

7 Annual Stroke risk from asymptomatic carotid stenosis = randomised trial? Marquardt et al. Stroke 2010

8 IPD Meta-analysis of VA, ACAS and ACST-1 Trials: 5000 patients randomised to Immediate CEA vs Medical Therapy alone Alison Halliday, Richard Bulbulia, Peter Rothwell, Richard Peto, Hongchao Pan for the VA, ACAS and CSTC groups Unpublished results: not yet available for reproduction

9 Nos. of patients (Immediate vs Deferred) Methods 5,000 individual patients in ACST-1, ACAS and VACS Trials VACS ACAS ACST (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 ( ) 4.2 ( ) 6.1 ( ) Median year of follow-up, as measured from the time of entry to that of the first stroke, death, loss to follow-up, or most recent examination

10 Q: What does CEA add to drug therapy? Analysis: 5000 patients in ACST-1, ACAS and VACS randomised trials of immediate vs deferred CEA, analysed by ALLOCATED treatment (ITT analyses) Almost all were on double, or on triple, drug therapy (Double therapy: BP lowering + anti-thrombotic) Triple therapy also includes a statin; does this so reduce risk that CEA is no longer worthwhile?

11 Summary: what does CEA add to drug therapy over the next 5-10 years after trial entry? Statins work: With CEA or without CEA, a statin approximately halves the stroke rate And CEA works: With a statin or without a statin, CEA approximately halves annual stroke rate Who benefits and which strokes are prevented?

12 Strokes do not always occur ipsilateral to that tight stenosis!

13 The proportional reduction is the same for fatal/disabling and for non-disabling strokes The largest absolute effect is on ipsilateral strokes, but other strokes are also reduced Risks are approximately halved for : - Men or Women, up to 75 years (few were >75) - High or low BP/cholesterol/glucose (diabetes) %+ stenosis, those with previous symptoms contralateral stenosis, or echolucent plaque

14 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.

15 High grade asymptomatic carotid stenosis: intervention vs medical treatment what changes have there been between the 1990s and the 2010s? Medical treatments have improved. but Only statins have made a real impact on stroke risk For truly asymptomatic patients (no symptoms, no brain infarcts) annual stroke risk may now be around 1.0%, but for patients with risk factors such as previous symptoms, it may well be 2-4% Risk of intervention has also halved and the decision to intervene depends on operator skill, proper patient assessment and good medical therapy before any intervention is undertaken

16 CEA vs CAS trials (symptomatic) 2000s 2010s how have stenting results changed? EVA 3-S (527 pts) SPACE-1(1214 pts) ICSS (1713 pts) First trials - More minor strokes after CAS After these early results many UK centres stopped/reduced CAS

17 But ICSS - longer term 4 year results Lancet (2014)

18 During 2000 s - procedural hazards of CEA and CAS improving in recent trials and registries 4.2 % 2.8 % 2.3 % 8.3% 6.9% 7.5% 6.1% 1.4 % 4.1% 3.5% 3.9% 2.3% 18

19 ACT 1 trial 5 year outcome NEJM, Major CVA/ death equal: 0.6% - Minor stroke 1.1% vs 2.4% - 5 yr stroke risk 5.3% vs 6.9%... non-inferior

20 CREST 10 year follow up NEJM, 2016 A. 30/7 composite outcome B. B. Any stroke or death

21 ACST-2 asymptomatic carotid surgery trial 2 the way forward for the 2010 s ( Intervention definitely planned, no recent symptoms CEA and CAS both possible, doctor and patient not certain that one procedure preferred over the other Higher risk patients can be included: older, previous symptoms or cerebral infarcts Long-term follow up

22 ACST-2 directly compares CEA vs CAS if CT/MR arch imaging shows patient is suitable for both procedures - then randomise 22

23 Our Patients Sex, Age, Co-morbidities: Men 70% Age (range 42-92) - median 69 years Ischaemic heart disease 37% Diabetic 30% Renal impairment 9% Stroke risk factors: Atrial Fibrillation 6% Age >75 yrs 26% Previous stroke symptoms or infarct 43% Blood pressure: 160mm Hg systolic 8% >90 mmhg diastolic 7%

24 Drugs at Trial Entry 85% lipid-lowering 88% anti-hypertensive 98% anti-thrombotic (anti-platelet +/or anti-coagulant)

25 Annual Follow up 2015 Lipid Lowering Treatment Atorvastatin 45% Simvastatin 40% Rosuvastatin 15% Other statins 8% Fibrates 5% Ezetimibe 5% On 2 lipid-lowering drugs 12%

26 Changes in Stent/ Protection Devices in ACST-2

27 Changes in Stent/ Protection Devices in ACST-2 Flow-reversal Protection device

28 Changes in Stent/ Protection Devices in ACST-2 Membrane Stent

29 And now: the surgical approach to stenting avoiding aortic arch atheroma, controlling flow reversal - results as good as surgery

30 Time trends in Stent use in ACST-2 100% 90% 80% 70% 60% 50% 40% 30% Membrane-mesh Hybrid Closed Open 20% 10% 0%

31 Jan-08 Jun-08 Nov-08 Apr-09 Sep-09 Feb-10 Jul-10 Dec-10 May-11 Oct-11 Mar-12 Aug-12 Jan-13 Jun-13 Nov-13 Apr-14 Sep-14 Feb-15 Jul-15 Dec-15 May-16 ACST-2 Progress two-thirds Recruited End Nov 0

32 UK 2 nd Best recruiter in ACST-2 every patient counts! Italy United Kingdom Serbia Sweden Germany Russia Belgium Czech Republic Hungary Poland Greece The Netherlands France Switzerland Spain Slovenia Other countries

33 Recruitment - Website October 2016 September 2016 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 32 East Tallinn Central Hospital 2 Novosibirsk Research Institute 3 Klinikum rechts der Isar Muenchen 2 Semmelweis Medical University 2 Albert Szent-Györgyi Medical Centre 1 Cheltenham General Hospital 1 Circolo University Hospital 1 Dedinje Cardiovascular Unit 1 Foothills Medical Centre 1 Guadalajara Hospital 1 Kent and Canterbury Hospital 1 Lasarettet Helsingborg 1 Malmo Vascular Centre 1 Mirano Hospital 1 Nottingham University Hospital 1 San Giovanni Di Dio 1 Santa Maria Hospital 1 Serbian Clinical Centre 1 Sodersjukhuset 1 St. Anna University Hospital Ferrara 1 Teaching Hospital Maribor 1 University of Basel 1 TOTAL SEPTEMBER 27 Website Front Page: Our new patient (s) were randomised from:

34 ACST-2 procedural hazards much lower than in symptomatic trials (CEA+CAS) and lower than in ACST-1 Disabling and fatal Stroke/MI 30 days: 1.0% (ACST-2) Lower than in previous trial of CEA 1.7% (ACST-1)

35 Safer Trials, Safer stenting Time to change your carotid practice? Many currently asymptomatic patients (with diabetes, previous symptoms/infarcts) are at substantial risk of future stroke Good medical treatment reduces stroke risk and carotid stenting and surgery reduce the risk still further Strokes are effectively prevented by CEA and by CAS Long term results of symptomatic and asymptomatic interventions have improved Stenting (and surgery) are safer, trials may well find that CEA and CAS are equally effective for long-term stroke prevention NICE endorses including patients in ACST-2 So, join the trial, change your practice!