1. Five-Year Cumulative Rates of Clinical Events after Cypher™ Stent Implantation: Insights from a Patient-Level Pooled Analysis of Four Randomized Trials Comparing Sirolimus-Eluting Stents with Bare Metal Stents
Adriano Caixeta, Roxana Mehran, Jeffrey W. Moses, George Dangas, Helen Parise, Ajay Kirtane, David R. Holmes, Charles O’Shaughnessy, Dennis Donohoe, Ronald Caputo, Dean J. Kereiakes, David O’ Williams, Martin B. Leon

2. Disclosure Statement of Financial Interest
I, Adriano Caixeta DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3. *Spaulding C, et al, N Engl J Med 2007;356:989-997.
Background
Sirolimus-eluting stents (SES) were approved for clinical use in 2003 to dramatically reduce the incidence of restenosis and rates of target lesion revascularization (TLR).
Delayed arterial healing response after drug-eluting stent (DES) implantation has raised concerns about the long-term safety of DES.
Although 4-year clinical outcomes in a pooled analysis of data from the four double-blind SES vs. bare metal stent (BMS) trials has been published recently*, 5-year clinical follow-up was scheduled by protocols in the four pivotal Cypher™ sirolimus-eluting stent (SES) and bare metal stent (BMS) randomized trial.
*Spaulding C, et al, N Engl J Med 2007;356:

4. Purpose
The aim of this study was to evaluate the 5-year safety and efficacy of SES compared with BMS.
The primary safety endpoint was death or myocardial infarction (MI). The secondary safety endpoint was stent thrombosis adjudicated according to the Academic Research Consortium (ARC) definition.
The primary efficacy endpoint was target vessel revascularization (TVR) up to 5 years. 3

5. Methods Patient-level Pooled Analysis RAVEL1 (N=238) SIRIUS2 (N=1058)
E-SIRIUS3
(N=352)
C-SIRIUS4
(N=100)
August 2000 and April 2002
1,748 patients at 115 international centers
De novo
15 to 32 mm long
RD 2.5 to 3.5 mm
Aspirin 81 to 325 mg
Clopidogrel 75 mg 2-3 mo
Cypher™ Sirolimus-eluting stent
(N=878)
BX Velocity Bare metal stent
(N=870)
1Morice MC,et al, N Engl J Med 2002;346:
2Moses JW, et al, N Engl J Med 2003;349:
3Schofer J, et al, Lancet 2003;362:
4Schampaert E, et al, J Am Coll Cardiol 2004;43: 4

6. Results Baseline Characteristics I SES BMS p-value Age 61.85 +/- 11.12/
0.91
Male gender, %
71.6%
71.5 %
0.96
Hypertension, %
63.8%
63.3 %
0.84
Hyperlipidemia, %
70.8%
71.8%
0.67
Current smoking, %
21.2%
24.5%
0.12
Diabetes mellitus, %
22.2%
26.8%
0.03
Prior MI, %
33.2%
35.7%
0.27
Prior PCI, %
22.9%
0.39
Prior CABG, %
7.5%
7.4%
0.93
Multivessel disease, %
38.6%
38.8%
0.92
Stable angina
23.1 %
25.0 %
0.37
Worsening angina
36.6%
33.3%
0.19
Rest angina
21.9%
21.8%
1.00

7. Results Procedure Characteristics SES BMS p-value Target lesion LAD, %
46.6%
46.7%
1.00
LCx, %
20.7%
20.8%
RCA, %
29.0%
29.1%
ACC/AHA lesion
A, %
7.0%
B1, %
33.9%
36.4%
0.29
B2, %
36.6%
38.1%
0.52
C, %
22.5%
18.5%
0.04
Vessel RD, mm
2.72
0.98
Total stent length, mm
22.87
22.45
0.31
Number of stents
1.42
1.39
0.38
IIbIIIa inhibitors, %
44.2%
43.4%
0.74

8. All Cause Mortality
8.9%
P=0.57
8.2%

9. Cardiac Death
P=0.55
4.4%
3.9%

10. Death and MI
15.1%
P=0.36
13.6%

11. Definite/Probable Stent Thrombosis (ARC defined)
2.0%
2.1%

12. Target Lesion Revascularization
P<0.01
24.7%
9.6%

13. Target Vessel Revascularization
30.1%
P<0.01
15.2%

14. Results Annualized Hazard Ratio per 100 pt-years
Year 1 Annual Hazard Rate per 100 pt-yrs
Year 2 to 5 Annual Hazard Rate per 100 pt-yrs
SES
BMS
P value
p-value
Death
1.3% (11)
0.8% (7)
0.3539
1.9%
0.7925
Cardiac Death
0.5% (4)
0.9916 1%
0.9%
0.5204
Non-Cardiac death
0.3% (3)
0.2101
1.1%
0.8003 MI
3.8% (33)
4.1% (36)
0.6966
0.7%
0.1081
QWMI
0.0% (0)
N/A
0.3%
0.2%
0.4659
NQWMI
0.8%
0.5%
0.124
TLR
4.3% (37)
20.5% (177)
<0.0001
1.3%
0.1268
TVR
9.5% (82)
25.3% (218)
2.4%
2.1%
0.2455
Remote TVR (non-TLR)
2.6% (23)
5.0% (43)
0.0117
1.4%
0.6753
Definite ST
0.9933
0.1%
0.1659
Definite + Probable ST
0.7% (6)
0.2192
0.4%
0.2257
Any (Definite + Probable + Possible) ST
1.6% (14)
0.1222
0.2769
Death/MI
4.9% (43)
4.6% (40)
0.7658
2.8%
0.3162
Death/Q-MI
2.2% 2%
0.6681
Death/MI/TVR
13.0% (114)
27.9% (242)
4.5%
4.2%
0.4038

15. Diabetic Subgroup: Death
16.1%
9.9%

16. Diabetic Subgroup: Death or MI
20.9%
17.4%

17. Conclusions
In a patient-level pooled analysis of the four SES and BMS randomized trials, no significant differences in the rates of death, MI, death/MI were observed at 5 years.
In pts with diabetes, however, treatment with SES was associated with a statistically higher incidence of death at 5 years.
No significant differences in the rates of any ARC-defined stent thrombosis were observed between SES and BMS at 5 years.
A significant difference in TVR rate was observed in favor of pts treated with SES at 5 years.
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