1. Critical Appraisal of the European CAS Trials
John. J Ricotta MD FACS
Professor Surgery Georgetown University
Chair of Surgery Washington Hospital Center CRT 2012

2. I have no real or apparent conflicts of interest to report.
John J. Ricotta, MD
I have no real or apparent conflicts of interest to report.

3. “What’s wrong with this picture?” Perspective
Interventionalists - CREST showed equivalence, MACE is what is important, European trials are fatally flawed
Surgeons – Stroke and death is what is important, not minor MI, major trials favor CEA for reduction of S/D, CREST results are great but not “real world “ for CAS
Neurologists – BMT has reduced stroke risk and direct BMT comparisons are required

4. Questions
What are the proper endpoints for comparisons between CAS and CEA?
Where CEA and CAS fairly compared in the European trials?
How applicable are the trial results to the real world ?

5. Proper Endpoints MACE vs. Stroke/Death
MACE treats all events as equivalent - Stroke, Death and MI all have different clinical implications, weighting was not used
The purpose of Carotid revascularization is to prevent stroke with minimal mortality and good long term outcome
4 yr mortality after any MI in CREST was 19.6% but was 20% after any stroke – both may be markers or reduced late survival

6. European Symptomatic Trials

7. European Trials EVA 3-S, SPACE, ICSS
Limited to Sx pts (1688 CAS, 1664 CEA)
Endpoints were Stroke and Death not MI
Operators did not have to have extensive CAS experience – although they did have to have EV experience
EPD not mandated : EVA 3S -92%, ICSS – 72%, SPACE - 27% no relation of EPD and stroke

8. Are the European Trials an Aberration?
How do the results compare with CREST? - only 52% of interventionists selected - lead in phase to assure AHA standards - 96% EPD use
How do the results compare with CAS registries?

9. 30 D Stroke and Death in Normal Risk Symptomatic Trial Pts
# CAS Pts
CAS S/D
# CEA Pts
CEA S/D
Risk Reduction
SPACE
598
7.7%
584
6.5%
1.18
EVA – 3S
261
9.6%
259
3.9%*
2.48
ICSS
828
7.1%
821
3.4%*
2.09
CREST
668
6.0%*
653
3.2%*
1.86
TOTAL
2356
7.3%
2317
4.2%*
( )

10. 30 Day Stroke and Death Rates in Multicenter Registries
11 Multicenter Registries Symptomatic Patients - Stroke and Death Rate 7.4% (CI ) Mark Grant MD MPH presented to MEDCAC Jan 26, 2011
Systematic review of 42 studies (4910 Sx pts) - Stroke/Death rate 7.3% (CI: ) Touze E et al. Stroke 2009;40:e

11. Annual CAS volume CMS Data (Nailamothu BK et al, JAMA 2011;306: 1338-43)
24701 CAS procedures
2339 operators
Median 3 CAS/yr
11.6% operators performed > 12 CAS /yr

12. Conclusions
There are design flaws in the European Trials comparing CAS and CEA in Symptomatic Pts
However their results are consistent with CREST, i.e. stroke and death RR of almost 2 fold with CEA vs. CAS
CREST is only trial where CAS meets AHA guidelines for S/D in Sx pts
European trials may mirror the real world experience of CAS in both operator volume and results

14. Stenting in Symptomatic Patients (Rothwell PM, Lancet Neurology 2009;8:871
“… The routine use of stenting in patients with recent symptoms of carotid stenosis in patients who are candidates for carotid Endarterectomy can no longer be justified”