1. Do we need more Carotid Trials after Crest to convince CMS
Mark Wholey M.D.UPMC Shadyside Hospt..

2. Mark H. Wholey, MD Consulting Fees Abbott Vascular Medrad, Inc.
Cordis Corporation
Covidien
AccessClosure, Inc.
Ownership Interest (Stocks, Stock Options or Ownership Interest)

3. Board Membership
CarMell Therapeutics
NIT

4. New Carotid Trials are Dead in the Water
If not dead then seriously questioned
Mark Wholey M.D. UPMC Shadyside,,Vascular Surgery

5. Do we need more trials since we have:
Experience with 45,000 patients
33 US Registries
8 Randomized CAS Clinical Trials
15 years of Experience with CAS .
4O years of Experience with CEA
.15 Years without reimbursement

6. MAE in high risk carotid stent IDE trials: 2002-2009 (n>4000)
11 device approval trials: all approved
…and rapidly improving outcomes
MAE in high risk carotid stent IDE trials: (n>4000)

7. Remarkable data for latest devices: all-comers N>1000 patients
Lumen/Invatec Fibernet (2008)
30 day MAE: 3.0%
WL Gore Flow Reversal System (2008)
30 day MAE: 2.9%
Abbott Vascular Gen V Emboshield (2008)
30 day MAE: 1.8%
Invatec ARMOUR (2009)
30 day MAE: 2.7%
(More experienced operators and better patient selection

8. CAS is technology dependent and continual improvement in stent design and embolic protection will occur.

11. Major Strokes less than 1% in both arms
Cranial nerve palsy 4% CEA .3% CAS

13. CREST CEA CAS Myocardial infarction 2.3% 1.1%
Strokes % % Major Strokes <1% <1%
Cranial Nerve Palsy % %

14. The rate of stroke and death in the surgical group was the lowest ever reported in a large stroke prevention trial.
It was also the lowest in any RCT with CAS.

15. NIH News
One of the largest stroke prevention trials ever (2502 patients). Efficacy and safety of the two procedures largely the same with equal benefits.

16. T. Brott, P.I. for CREST
“Crest results show we have two safe and effective methods to treat carotid artery disease, tried and true CEA and the new kid on the block CAS.”

17. Too Long String Sign Mobile Clot Too Tortuous
The carotid trials; Stenting patients who should not have been enrolled
Dangerous Common Carotid
Too Long String Sign Mobile Clot Too Tortuous

18. PROBLEMS of the aortic arch
Complexities of the aortic arc are responsible for almost all technical failures
More Trouble
Ideal
Trouble

19. Everybody makes mistakes

20. Eva-3s trial Prospective, randomized trial 257 CEA 247 CSA
20 academic and 10 non-academic centers in France
Symptomatic >60% stenosis
Stroke, death (6 months)
CEA %
CSA 11.7% OR
Trial stopped for both safety issues and futility
NEJM 2006;355:

21. Space trial 1200 Symptomatic Pts randomized to CEA vs CAS
Primary endpoint: stroke, death at 30-days:
6.84% CAS VS. 6.34% CEA (p=0.09)
Failed to prove Non-inferiority of CAS
RESTENOSIS
Most cases occurred within first 6 Mos.
28 Cases CAS vs. 12 CEA
Lancet 2006;368:

22. International Carotid Stent Study (ICSS)
Largely UK effort
Randomized 1710 symptomatic patients to either CEA or CAS
3 year primary endpoint: fatal or disabling stroke in any territory
Interim analysis published in Lancet
120 day death, stroke, or MI
CEA operators: >50 operations/>10 per year
CAS operators: >50 stent procedures (anywhere), 10 lifetime CAS cases---fellow-level experience
Inexperienced operators had to complete 20 randomized cases satisfactorily to be released

23. ICSS: further observations
Very low rate of MI in both groups suggests that they weren’t routinely assessed (unclear from Methods)
Embolic protection not mandated and choose whatever stent you want
Major stroke was ~2% in each group, double what is seen in US
(One operator ,enrolled 11 pts and 5 disabling strokes)
Poorly trained operators getting poor results

24. We Need More Carotid Trials before We Decide
CEA vs. Stenting in symptomatic octogenarians
CEA vs. Stenting in asymptomatic octogenarians
CEA vs. Stenting in symptomatic low risk patients
CEA vs. Stenting in asymptomatic low risk patients
CEA vs. Stenting in patients with prior CVA
CEA vs. Stenting in African Americans
Stenting vs. optimal medical therapy in asymptomatic high risk patients
CEA vs. Medical management in transatlantic vs. transpacific Tacit vs Pacit
Stenting with Bivalurudin vs. Heparin
Stenting with femoral access vs. radial access
Stenting with 300 mg loading dose of Clopidrogel vs. 600 mg
Stenting with 24 observation in the hospital vs. same day discharge
Stenting in smaller community hospital vs. tertiary care center
Stenting with your left hand vs. your right hand
This Nonsense is Over

25. THE CAROTID TRIALS
WHEN IS ENOUGH, ENOUGH?

26. No one is willing fund additional Carotid Trials?
Volatile U.S. equity markets
Eurozone sovereign debt with Ireland, Greece,Spain and Portugal almost bankrupt
Japan bear market for 20 years.

27. Industry will not fund these trials?.
Absent re-imbursement
Rejection by CMS – in spite of results Regulatory and FDA approval issues have been a constant battle.
Why sould they ; CAS has been a loser

28. P.T. Barnum said “There’s a sucker born every minute.”
Further investing in carotid trials is a suckers game

29. 1. A Billionaire that wants to become a Millionaire
So who will invest in CAROTID TRIALS without reimbursement ? Some sucker or someone stupid enough to do it.
1. A Billionaire that wants to become a Millionaire
2.Maybe Bernie Madoff
3.With Eurozone debt Greece, Ireland, Spain ,Portugal can’t buy each other lunch let alone a 1million dollar trial. They are bankrupt.

30. CAS and CEA trials have become an Economic Nightmare

31. We have spent over 300 million dollars on carotid trials in the USA CREST was a 100 million dollar trial
There is no way we can afford, in the current economic environment, another carotid trial

32. Further carotid trials would be a waste of time and tax payers money
The public would not allow it

33. will any of these leaders support another 100 million dollar trial

34. Conclusion
We have enough evidence to support either CAS or CEA but we do not need more trials to duplicate data we already have. You make your own decision. We don’t care.
And we don’t need a trial to know this asymptomatic patient needs carotid repair and not BMM % and 70% lesions don’t need any trial.!!!

35. This was the take home message from CMS
This was the take home message from CMS .Let’s hope Crest will change this attitude .

36. Do we need more trials since we have:
Experience with 45,000 patients
33 US Registries
8 Randomized CAS Clinical Trials
15 years of Experience with CAS .
4O years of Experience with CEA
.15 Years without reimbursement

37. The government has bigger things on its mind

38. This is a smart Doctor; Don’t be a sucker.

39. No one is willing to fund additional Carotid Trials?
Deteriorating unemployment
Volatile U.S. equity markets
Eurozone sovereign debt with Ireland, Greece,Spain and Portugal almost bankrupt
Japan bear market for 20 years.

40. What Sucker will fund these trials?
Industry will not. Why would they?
Absent re-imbursement
Rejection by CMS – in spite of results Regulatory and FDA approval issues have been a constant battle.

41. We have enough of evidence to support either CAS or CEA, but we do not need more trials to duplicate data that already exists.

43. MAE in high risk carotid stent IDE trials: 2002-2009 (n>4000)
11 device approval trials: all approved
…and rapidly improving outcomes
MAE in high risk carotid stent IDE trials: (n>4000)

44. POSTMARKET SURVEILLANCE REGISTRIES
Name (Source)
CAPTURE (Catheter Cardiovasc Interv. 2007;69: ; Ann Surg 2007;246: )
CAPTRURE 2 (Stroke. 2010;4: )
CASES (Catheter Cardiovasc Interv. 2007;70: ; J Am Coll Cardiol. 2010;56:49-57)
CHOICE ( trials/TrailDetail.aspx?tid=1033)
aNonhierarchial
Name (Source)
CREATE PAS (ev3 Inc.)
CRISTALLO (J Endovasc Ther. 2008; 15: )
EXACT ( /TrialDetail.aspx?tid=774; Presented at the i2 Summit 2007: Emboshield and Xact Post Approval Cartoid Stent Trial)
SAPPHIRE WW (Catheter Cardiovasc Interv. 2009;73: )
SONOMA (
aNonhierarchial
Name (Source)
ARCHER (J Vasc Sug. 2006;44: )
ARMOUR (Invatec)
BEACH (j Am Coll Cardiol. 2008;51: ; Boston Scientific Corporation)
CABERNET (Boston Scientific Corporation)
CREATE (ev3 Inc; J Am Coll Cardiol. 2006;47: )
CREATE SpideRX Arm (Published online in J Interv Cardiol. July 8, 2010)
EMPIRE (Published online in Catheter Cardiovasc Interv. Sept. 7, 2010)
EPIC Pivotal Trial (Lumen Biomedical)
aNonhierarchial
POSTMARKET SURVEILLANCE REGISTRIES

45. We Need More Carotid Trials before We Decide
CEA vs. Stenting in symptomatic octogenarians
CEA vs. Stenting in asymptomatic octogenarians
CEA vs. Stenting in symptomatic low risk patients
CEA vs. Stenting in asymptomatic low risk patients
CEA vs. Stenting in patients with prior CVA
CEA vs. Stenting in African Americans
Stenting vs. optimal medical therapy in asymptomatic high risk patients
CEA vs. Medical management in transatlantic vs. transpacific Tacit vs Pacit
Stenting with Bivalurudin vs. Heparin
Stenting with femoral access vs. radial access
Stenting with 300 mg loading dose of Clopidrogel vs. 600 mg
Stenting with 24 observation in the hospital vs. same day discharge
Stenting in smaller community hospital vs. tertiary care center
Stenting with your left hand vs. your right hand
This Nonsense is Over

46. Will this be the last US Cartoid Trial?
The Crest Trial
Will this be the last US Cartoid Trial?