1. Large-Scale Registry Examining Safety and Effectiveness of Zotarolimus-Eluting and Sirolimus-Eluting Stents in Patients with Coronary Artery Disease
Western Denmark Heart Registry
Michael Maeng, Anne Kaltoft, Lisette Okkels Jensen,
Hans-Henrik Tilsted, Per Thayssen,
Klaus Rasmussen, Evald Høj Christiansen,
Morten Madsen, Søren Paaske Johnsen,
Henrik Toft Sørensen, Jens Flensted Lassen,
Leif Thuesen 1

2. Large-Scale Registry Examining Safety and Effectiveness of Zotarolimus-Eluting and Sirolimus-Eluting Stents in Patients with Coronary Artery Disease
Conflicts of interests for Leif Thuesen, M.D.
Cordis, Johnson & Johnson:
Research grants, speaker’s fees.
Medtronic:
Advisory board, research grants, speaker’s fees. 2

3. Background (1)
The randomized 436-patient ENDEAVOR III trial compared the zotarolimus-eluting Endeavor stent with the sirolimus-eluting Cypher stent
More angiographic late lumen loss
Greater angiographic restenosis
Similar target lesion revascularization rate
Limitations; short term (9 months) follow-up and a selected patient population 3

4. Background (2)
Based on the phosphorylcholine coating and larger late lumen loss, the Endeavor stent stent might be associated with less stent thrombosis but more restenosis than other drug-eluting stents 4

5. Purpose
To compare the effectiveness and safety of the Endeavor versus the Cypher stent in a large registry reflecting every-day clinical practice 5

6. Endpoints Safety Mortality Effectiveness Clinically driven TLR
Myocardial infarction >28 days
Stent thrombosis
Effectiveness Clinically driven TLR
Clinically significant in-segment restenosis

7. Western Denmark Heart Registry
Covers the  3.0 million inhabitants in Western Denmark
Collects detailed patient and procedure data on all coronary interventions including CABG
Three high-volume interventional centers cover the entire region 7

8. Material and Methods (I)
Patients
All patients treated with Endeavor or Cypher stent from August 2005 to October 2007
Patients: 6,122
Lesions: 8,185
Follow-up
From 40 to 823 days after index PCI
Ascertained from 8

9. Material and Methods (II)
Patients treated during the study period
All PCI-treated patients 10,992
Study population (Cypher/Endeavor) 6,122
Other DES ,050
BMS ,125
POBA, other intervention 1,695
Ascertained from 9

10. Material and Methods (III)
MI and death
Ascertained from national databases
Target lesion revascularization (TLR)
Definite stent thrombosis
In-segment restenosis
Obtained from the WDHR by review of all cases of target vessel revascularization occurring during the study period
Ascertained from 10

11. SO III patients in registry
Registry Study
SORT-OUT III
Registry
Inclusion period
August 05 - October 07
PCI centres
n=3
Patients
n=6,122
Follow-up
days
RCT
Inclusion period
January 06 - August 07
PCI centres
n=5
Patients
n=2,334
Follow-up
270 days
Ascertained from
SO III patients in registry
n=1,868 (30.5%) 11 11

12. Statistics
A Cox’s proportional hazards regression model controlling for age, gender, indication for PCI, diabetes, stent length, number of stents, number of lesions treated, and procedure time was used to compute hazard ratios as estimates of relative risks for each endpoint 12

13. Selected Patient Characteristics
Cypher
Endeavor p
No of patients
3,840
2,282
Age (yrs)
64.7
66.7
<0.001
Male (%)
74.7
72.1
<0.05
BMI (kg/m2)
27.3
27.2 ns
Diabetes (%)
15.8
15.0
Hypertension (%)
49.4
54.1
Lipid-lowering therapy (%)
62.6
65.7
Previous CABG (%)
8.8
9.4
Previous PCI (%)
32.2
33.7
Previous MI (%)
35.0
36.7

14. PCI Indication Cypher Endeavor p Stable angina (%) 41.9 40.5
Unstable angina (%)
30.2
33.4
STEMI (%)
24.6
22.4
Other (%)
3.3
3.7
<0.05

15. Selected Procedure Characteristics
Cypher
Endeavor p
No of lesions
5,095
3,090
No of lesions/patient
1.3
1.4 ns
Lesion length (mm)
16.2
15.7
<0.05
Stent length (mm)
20.2
19.9
<0.001
Ref. vessel diameter
3.2
Lesion type
Type A
21.6
21.3
Type B
50.2
47.0
Type C
28.2
31.7
Procedure time (min)
26.6
28.6

16. All Cause Mortality All cause mortality (%) Endeavor Cypher
Cypher (n)
Endeavor (n) 16

17. All Cause Mortality Adjusted RR (95% CI) = 1.34 (1.04 – 1.71) p=0.02
Endeavor
Cypher
Cypher (n)
Endeavor (n) 17

18. Cardiac Mortality Cardiac mortality (%) Endeavor Cypher
Cypher (n)
Endeavor (n) 18

19. Cardiac Mortality Adjusted RR (95% CI) = 1.83 (0.99 – 3.41) p=0.06
Endeavor
Cypher
Cypher (n)
Endeavor (n) 19

20. Myocardial Infarction > 28 days
Late myocardial infarction (%)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 20

21. Myocardial Infarction > 28 days
Adjusted RR (95% CI) = 1.01 (0.88 – 1.16)
p=0.87
Late myocardial infarction (%)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 21

22. Definite Stent Thrombosis (patient)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 22

23. Definite Stent Thrombosis (patient)
Adjusted RR (95% CI) = 2.06 (0.77 – 5.51)
p=0.15
Definite stent thrombosis (%)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 23

24. Definite Stent Thrombosis (lesion)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 24

25. Definite Stent Thrombosis (lesion)
Adjusted RR (95% CI) = 1.78 (1.06 – 3.00)
P<0.05
Definite stent thrombosis (%)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 25

26. Target Lesion Revascularization (patient)
TLR (%)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 26

27. Target Lesion Revascularization (patient)
Adjusted RR (95% CI) = 2.25 (1.42 – 3.56)
p=0.0005
TLR (%)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 27

28. Target Lesion Revascularization (lesion)
TLR (%)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 28

29. Target Lesion Revascularization (lesion)
Adjusted RR (95% CI) = 2.39 (1.82 – 3.13)
P<0.0001
TLR (%)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 29

30. In-segment Restenosis (patient)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 30

31. In-segment Restenosis (patient)
Adjusted RR (95% CI) = 2.25 (1.33 – 3.81), p=0.003
In-segment restenosis (%)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 31

32. In-segment Restenosis (lesion)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 32

33. In-segment Restenosis (lesion)
Adjusted RR (95% CI) = 2.44 (1.76 – 3.37)
P<0.0001
In-segment restenosis (%)
Endeavor
Cypher
Cypher (n)
Endeavor (n) 33

34. Limitations
In the present registry, the Cypher and Endeavor stent groups were not comparable.
We adjusted for the most important predictors.
It is unlikely that we made a complete compensation for selection bias at patient or operator level.

35. Conclusions
Within the current follow-up period, none of the safety endpoints indicated better safety profile of the Endeavor stent vs. the Cypher stent
The Endeavor stent seemed to be less effective than the Cypher stent concerning risk of clinical significant restenosis and target lesion revascularization