Trial update – 1169 Patients so far-Well done, what’s next?

1. Trial update – 1169 Patients so far-Well done, what’s next? Alison Halliday, Professor of Vascular Surgery, University of Oxford 4th April 2013

2. 40 years of carotid surgery trialsCarotid endarterectomy [CEA] vs no intervention- 1980s: “symptomatic” patients- 1990s: asymptomatic patientsCEA vs carotid stenting[CAS] - 2000s: symptomatic patients-2010s: asymptomatic patients

3. 1990s: what about asymptomatic patients?

4. ACST-1: 10-year stroke risk reduced by surgery (CEA) 20 ACST-1 15 Control 15% % 10 CEA 10% 5 2p = 0.0006 0 Years 0 5 10

5. Surgery reduces 10-year stroke risk for men & women under 75 years

6. ACST-1 changed practice worldwide(Lancet 2004, 2010) Over 1000 citations so far….

7. Wide variation in current practice North America 60% surgery, 40% stenting Continental Europe 50% surgery, 50% stenting United Kingdom 90% surgery, 10% stenting

8. Annual numbers of carotid procedures(CEA or CAS) North America >100,000 pa, 95% asymptomatic Continental Europe + UK >100,000 pa, 60% asymptomatic

9. Poor outcomes after endovascular treatment of symptomatic carotid stenosis: time for a moratorium Lancet Neurology 2009 ….Most stenting for symptomatic stenosis (has) a greater procedural risk of stroke and a worse long-term outcome than ..endarterectomy ……….Routine use of stenting in (symptomatic) patients suitable for endarterectomycan no longer be justified… …Vague and non-evidence-based categorisations, such as “high risk for surgery,” which have been systematically misused to justify the uncontrolled roll-out of carotid stenting in many centres, must stop……..

10. Meta-analysis Symptomatic Stenting vs Surgery trials (Lancet 2010)

11. Carotid artery stenting versus surgery: adequate comparisons?Lancet Neurology 2010, 339–341 Correspondence ‘As randomised clinical trials are the gold standard of clinical investigation, it seems unwise to challenge them. However, for the comparison of CAS versus CEA, most of the randomised trials should be considered not only scientifically but also ethically questionable because the endovascular experience required for interventionalists to be eligible for the studies was minimal’

12. Carotid artery stenting versus surgery: adequate comparisons? – the Trials’ experienceLancet Neurology, April 2010, Pages 341–342Martin M Brown, Jean-Louis Mas, Peter A Ringleb, Werner Hacke

13. After the symptomatic trials CAS may be getting better– but what has changed? • Experience, time and devices • Open vs closed cell stents (ICSS data) • Filters vs no filters • New devices – direct puncture, reverse flow, others arriving • (And possibly MEDICAL treatments are better)

14. Years of experience – lower risk Meta-regression analysis

15. More Procedures – lower risk

16. Muller-Hulsbeck S et al. JEVT 2009;16:168-177

17. Does Free Cell Area Influence the Outcome in Carotid Artery Stenting ? (N =3179 X-act, Nexstent, Wallstent, Precise, Protégé, Acculink, Exponent) Bosiers M e al EJVES 2007;33:135 - 141

18. After the symptomatic trials CAS may be getting better– but what has changed? The CREST Trial (NEJM 2010) 2500 patients About half were asymptomatic No significant differences found overall Symptomatic patients still higher risk from CAS Asymptomatic = similar risks (but numbers too small) So ACST-2 (CAS vs CEA) is important for the FUTURE

20. CREST: Major Stroke/Death (CAS) during Enrollment 50% Trial Enrollment CAS = 0.4% CEA = 0.4%

21. Statins lower stroke risk in CEA (J Vasc Surg 2005;42:829-836)

22. Future of CEA vs CAS trials - Reducing procedural hazards (stent design, insertion, drug elution) - Changing spectrum of patients (older, chronically ill, screen-detected) And.. • Improving medical treatments Trials will need VERY large numbers of patients, because they study moderate effects BUT their results can change future treatments worldwide

23. If a patient with no recent symptoms has 70-99% carotid stenosis should any carotid procedure be done?If Yes: Consider ACST-2A large simple trial of CEA vs CAS (where both procedures are appropriate) planning to recruit 5000 patients by 2019, and follow to 2025

24. When intervention seems clearly needed • and, after arch imaging, both procedures are appropriate • Consider patients for ACST-2 Surgery Stenting

25. ACST-2 – current status 1169 patients recruited (April 2013) Soon will have more asymptomatic patients randomised than any other trial Many more Centres and Patients needed – we welcome our first from Japan!

28. Patient Characteristics - Balance at trial entry

29. Patient Characteristics - Balance at trial entry

30. Patient Characteristics - Balance at trial entry

31. Patient Characteristics - Balance at trial entry

32. If Procedure not yet done…. • Return 1 Month Follow-up Form recording why procedure not done or delayed • Once the procedure has been done, please return a 1 Month Form to us with the details

33. Type of stent used in CAS(Any CE-approved device allowed)

34. Straight (54%) Tapered (46%)

35. Cerebral protection (CP) devices used in ACST-2

36. ACST-2 Medical treatment one month after Intervention

37. Future of carotid surgery trials - Improving medical treatments - Reducing procedural hazards (stent design, insertion, drug elution) - Different spectrum of patients (older, chronically ill, screen-detected) - Collaboration – with SPACE-2, ECST-2 and CREST-2

38. ACST-2 is funded by the UK Health Technology Assessment Programme and the BUPA Charitable Foundation and organised within