1. The Impact of prolonged antiplatlelet therapy Following DES
Ron Waksman, MD
Washington Hospital Center

2. Ron Waksman, MD DISCLOSURES Consulting Fees Grants/Contracted Research
Abbott Vascular, Biotronik, Medtronic CardioVascular, Inc, Boston Scientific Corporation
Grants/Contracted Research
Abbott Vascular, Biotronik, Boston Scientific Corporation, The Medicines Company, GlaxoSmithKline, Schering-Plough, sanofi-aventis U.S. LLC

3. IMPACT OF PROLONGED ANTIPLATELET THERAPY
Efficacy: Reduction of Ischemic events and stent thrombosis
Safety: Increased the risk of bleeding major minor and nuisance, Rebound phenomenon?
Need for interruption
Cost and cost effectiveness the trade off efficacy versus safety

5. Antiplatelet Trialists’ Collaboration. BMJ 1994;308:81–106.

6. McFadden EP et al. Lancet 2004; 364:1519–21

7. ACC/AHA/SCAI Guidelines Class 1 Level of Evidence B*
For all post-PCI stented patients receiving a DES, clopidogrel 75 mg daily should be given for at least 12 months if patients are not at high risk of bleeding.
Does Prolonged DAPT Prevent Stent Thrombosis ???
Within 6 months, yes-numerous studies have shown that thienopyridine discontinuation within 6 months after DES is a major risk factor for stent thrombosis
After 6 months, who knows? 7

8. DES (but not BMS) Pts Who Are Event-free at 6 Months on Clopidogrel have Lower 2 Year Death/MI
Eisenstein EL et al. JAMA. 2007;297:

9. Spertus JA et al. Circulation 2006;113:2803-9.

10. Airoldi F et al. Circulation 2007;116:745-54

11. Airoldi F et al. Circulation 2007;116:745-54

12. Outcomes by Stent Type & Clopidogrel Duration in Diabetics 6-Month Landmark Analysis in event-free pts (N=749)
Brar SS et al. JACC. 2008;51:2220-7

13. Serebrauny V. JACC 2004 13

14. Rebound CV Events After Clopidogrel Discontinuation 3137 pts with ACS were discharged from 127 VA hospitals on clopidogrel (50% after PCI, 50% medical Rx) in whom clopiodgrel was subsequently d/c’d at mean 302 days (medically treated pts) and 278 days (PCI treated pts). Pts were then followed ~6 mos off clopidogrel. Instantaneous rate of death or MI per person-day
Ho PM et al. JAMA 2008;299:532-9

15. Safety of Long-term Clopidogrel 3 Placebo Controlled Trials

18. The Impact of “Nuisance” Bleeding on Clopidogrel Compliance in Patients undergoing Intracoronary Drug-Eluting Stent Implantation
Ron Waksman, Probal Roy, Laurent Bonello, Rebecca Torguson,
Axel de Labriolle, Gilles Lemesle, Tina L. Pinto Slottow,
Daniel H. Steinberg, Kimberly Kaneshige, Zhenyi Xue,
Lowell F. Satler, Kenneth M. Kent, William O. Suddath,
Augusto D. Pichard, Joseph Lindsay.
Washington Hospital Center, Washington DC, USA
Mister the chairmen
Ladies and gentlemen
I particularly appreciate to be here at the AHA congress and to present to you the result of our study entitled: …
Roy P, Waksman R, American Journal of Cardiology 2008 18

19. Incidence of Bleeding
837 patients reported bleeding events (cumulative incidence 32.4%).
Percentage distribution of bleeding types (nuisance, internal and alarming)
0.7%
13.6%
85.7%
Roy P, Waksman R, American Journal of Cardiology 2008 19

20. Time and duration of Nuisance Bleeding
Majority of the patients have daily episodes of Nuisance bleeding
Roy P, Waksman R, American Journal of Cardiology 2008

21. Aspirin and Clopidogrel discontinuation as a result of bleeding type.
Alarming and internal bleeding was associated with higher rates of anti-platelet discontinuation. In patients with “nuisance” bleeding, 11.1% and 5.0% ceased clopidogrel and aspirin, respectively
Roy P, Waksman R, American Journal of Cardiology 2008 21

22. THE SENS STUDY Outcome of Non-cardiac Surgical Procedure and Brief Interruption of DAPT within 12 Months Following Endeavor Implantation

23. SENS Outcome of Non-cardiac Surgical Procedure and Brief Interruption of DAPT within 12 Months Following Endeavor Implantation
Purpose
To examine the safety of the Endeavor stent associated with non-cardiac surgical procedure and brief interruption of dual anti-platelet agents within 12 months following stent implantation
Study Design
Retrospective study of the 194 out of 3099 patients (6.2%) who had a brief interruption of DAPT1 due to a noncardiac surgical procedure
Trial locations: 11 sites in South Korea
Primary endpoint: 30-day MACE including death, MI and TLR
Primary investigator: Jin Won Kim, MD
1 Both clopidogrel and ASA

24. Early Surgery vs Late Surgery
Early surgery group (3 months,
n = 34)
Late surgery group
(3-12 months,
n = 160)
P Value
Age (yrs), Male (%)
62.2/63.5
63.1/50.9 NS
Lesion type (B2/C) (%)
73.6
72.8
Stent number
1.4
1.5
Stent diameter (mm)
3.11 ± 0.52
3.08 ± 0.47
Total stent length (mm)
33.0 ± 16.7
29.2 ± 19.5
Major surgery (%)
20.5
22.6
Days from stenting to surgery
56.5
233.7
<0.001
DAP withdrawal (days)
13.4
14.8
NS = not significant; DAP = dual antiplatelet agents

25. MACE Early Surgery vs Late Surgery Late Surgery Group
Early Surgery Group
8.9%
3/34
2 Death
1 MI
0.6%
1/159
P < 0.001

26. Incremental Costs/Cost Offsets with Prasugrel*
Rehospitalization
Costs
Other Vasc. Interventions
$12
Bleeding $69
Other $82
Angina $20
CABG -$21
MI (no PCI) -$57
Total -$517
PCI -$621
Prasugrel
Clopidogrel
Difference
(P-C)
Index Hospitalization Costs
$19,740
$19,752
-$12
Rehospitalization Costs
$4,465
$4,982
-$517
Study Drug Costs
$1,862
$1,554
$308
TOTAL COSTS
$26,067
$26,288
-$221

27. Cost-Effectiveness: Days 1-30
Cost = -$192 D Life Exp. = yr
ICER = Dominant
% Dominant: 89.7%
D Cost (Prasugrel – Clopidogrel)
% <$50,000/LY: 97.7%
D Life Years (Prasugrel – Clopidogrel)

28. Cost-Effectiveness: Days 31-EOS
Cost = -$28 D Life-Exp = yr
ICER = Dominant
% Dominant: 54.3%
D Cost (Prasugrel – Clopidogrel)
% <$50,000/LYG: 96.6%
D Life Years (Prasugrel – Clopidogrel)

29. Impact of Generic Clopidogrel
Treatment Over Full Trial Duration
Cost of Generic Clopidogrel = $1/day
Cost = +$996 D Life-years= 0.102
ICER = $9,727/LYG
% Dominant: 0%
D Cost (Prasugrel – Clopidogrel)
% <$50,000/LYG: 98.2%
D Life Years (Prasugrel – Clopidogrel)

30. Conclusions
For patients undergoing PCI in the ACS setting, treatment with prasugrel compared with clopidogrel is highly cost-effective– and in many cases cost- saving– over both the subacute and longer term phases of treatment
Compared with generic clopidogrel (expected cost $1/day), prasugrel was cost saving during the first 30 days but resulted in higher costs (by ~$800/pt) beyond this time period.
Nonetheless, formal cost-effectiveness analysis suggests that this higher cost may be justified based on projected gains in long-term survival