1. Second Generation DES Associated with Less Late and Very Late Stent Thrombosis Compared to First Generation DES
Donald E. Cutlip, MD
Beth Israel Deaconess Medical Center
Harvard Clinical Research Institute
Harvard Medical School

2. Disclosures
Salary support from Harvard Clinical Research Institute, an academic research organization that performs contracted research for many coronary device manufacturers
Principal Investigator – Medtronic dual anti- platelet therapy after stenting trial (paid to institution)
Consultant – St. Jude Medical (fellows’ course speaker)

3. Preliminary Considerations
Impact of late and very late ST relative to early ST
Differences within and between DES “generations”
Is study duration of follow-up adequate to address the question?
Duration of DAPT and impact on late and very late ST rates

4. Timing of Stent Thrombosis
Academic Research Consortium
Early (0-30 days)
Acute (0-24 hours)
Subacute (1-30 days)
Late (31 days – 1 year)
Very Late (> 1 year)

5. Timing of Stent Thrombosis
Five Year Results of SES and PES RCTs

6. Timing of Stent Thrombosis
Late Results High Risk Patients

7. Timing of Stent Thrombosis
ACS Patients
TRITON TIMI 38
ARC Definite or Probable ST
HORIZONS-AMI
ARC Definite or Probable ST
S Wiviott et al. Lancet 2008;371:
G Stone et al. NEJM 2009;360:

8. Early or Late ST & 2nd Generation DES Zotarolimus-Eluting Stent
Pooled Endeavor
Endeavor 4
SORT-OUT III
N= 2132
N= 596
N= 760
N= 756
N= 1162
N= 1170
L Mauri et al JACC Int 2010;3;1240-9
MB Leon et al JACC 2010;55;543-54
K Rasmussen et al Lancet 2010;375;1090-9

9. Early or Late ST & 2nd Generation DES Everolimus-Eluting Stent
Pooled SPIRIT II, III, IV and COMPARE
E Kedhi et al. AHA 2010

10. Early or Late ST & 2nd Generation DES Everolimus-Eluting Stent
EES vs SES – SORT-OUT IV
SES N= 1384
EES N= 1390
SES N= 1384
EES N= 1390
LO Jensen et al. TCT 2010

11. Very Late Stent Thrombosis Are 2nd generation DES safer?
Is there increased risk after PES vs SES?
Meta analysis of clinical trials, ST >6 months lower for SES vs PES (HR 0.5, 95% CI )
Network meta-analysis, LST + VLST higher for PES vs BMS or SES.
PES independent predictor of LST or VLST in at least 2 large registries:
Western Denmark, (RR 3.8, 95% CI )
Bern-Rotterdam, (HR 1.7, 95% CI )
A Schömig et al. JACC 2007;50:1373
C Stettler et al. Lancet 2007;370:937-48
LO Jensen et al. Eurointerv 2010;5:
P Wenaweser et al. JACC 2008;52:

12. Very Late Stent Thrombosis EES versus PES
SPIRIT III Four Years – ARC Definite or Probable ST
G Stone et al. TCT 2010

13. Very Late Stent Thrombosis ZES versus PES
Endeavor IV– Three Year ARC Definite or Probable ST
(0.1% vs. 1.6%, p=0.004)
MB Leon et al JACC Intv 2010;3;

14. ZES Pooled Stent Thrombosis5% 3% 0% 4% 2% 1%
BMS
ZES
2132 ZES pts
2 ST year 1-2; 1 ST after year 2
Cumulative Incidence of
Def/Prob Thrombosis
Adjusted HR = 0.50 ( )
1.7%
Indeed with data now over 4 years – in a non randomized comparison of the ZES experiecne compared with the BMS counterpart the overall rate of ST with ZES is actually lower. Events after1 year are very infrequent in both devices with only 2 ZES ST after 1 year and 1 after 2 years in the combined experience with nearly 1200 pts now out to 5 years.
0.8%
360
720
1080
1440
1800
Time after Initial Procedure (days)
L Mauri et al JACC Int 2010;3;1240-9

15. % Thienopyridine Usage Over Time
DAPT Duration
% Thienopyridine Usage Over Time
SPIRIT III
ENDEAVOR IV
Time
EES
PES
12 M
71%
24 M
56%
60%
36 M
51%
48 M
49%
46%
Time
ZES
PES
12 M
58%
57%
24 M
65%
71%
36 M
48%
52%
G Stone et al. TCT 2010
M Leon et al. TCT 2009

16. Bioabsorbable Polymers
Biolimus vs. Sirolimus-Eluting - LEADERS Trial
BES
SES
P Serruys et al TCT 2010

17. Bioabsorbable Everolimus-Eluting Coronary Stent System (BVS)
Bioabsorbable DES
Bioabsorbable Everolimus-Eluting
Coronary Stent System (BVS)
ABSORB-A
N=30
No stent thrombosis to 4 years
ABSORB-B
N=101
No stent thrombosis to 9M
Late loss = 0.43
(recoil)
Late loss = 0.19
P Serruys AHA 2010

18. Conclusions
Early stent thrombosis remains a critical determinant of overall stent thrombosis risk (especially in high-risk lesions)
EES may have slightly lower risk for early stent thrombosis compared with PES
ZES appears to have the lowest risk for very late stent thrombosis but no evidence for lower early risk
The optimal duration of dual anti-platelet therapy to mitigate the risk of stent thrombosis for a given DES remains unknown and must be considered in stent vs stent comparisons