Large-Scale%20Registry%20Examining%20Safety%20and%20Effectiveness%20of%20Zotarolimus-Eluting%20and%20Sirolimus-Eluting%20Stents%20in%20Patients%20with%20Coronary%20Artery%20Disease

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

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,
speakers fees. Medtronic Advisory board,
research grants, speakers fees.
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

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
5
Purpose
To compare the effectiveness and safety of the
Endeavor versus the Cypher stent in a large
registry reflecting every-day clinical practice
6
Endpoints

• Safety Mortality
• Myocardial infarction gt28 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
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

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 1,050
• BMS 2,125
• POBA, other intervention 1,695

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

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Registry Study
SORT-OUT III

• Registry
• Inclusion period
• August 05 - October 07
• PCI centres
• n3
• Patients
• n6,122
• Follow-up
• 40 - 823 days

RCT Inclusion period January 06 - August 07 PCI
centres n5 Patients n2,334 Follow-up 270 days

SO III patients in registry n1,868 (30.5)
12
Statistics

• A Coxs 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

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Selected Patient Characteristics
Cypher Endeavor p
No of patients 3,840 2,282
Age (yrs) 64.7 66.7 lt0.001
Male () 74.7 72.1 lt0.05
BMI (kg/m2) 27.3 27.2 ns
Diabetes () 15.8 15.0 ns
Hypertension () 49.4 54.1 lt0.001
Lipid-lowering therapy () 62.6 65.7 lt0.05
Previous CABG () 8.8 9.4 ns
Previous PCI () 32.2 33.7 ns
Previous MI () 35.0 36.7 ns
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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
lt0.05
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 lt0.05
Stent length (mm) 20.2 19.9 lt0.001
Ref. vessel diameter 3.2 3.2 lt0.001
Lesion type lt0.001
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 lt0.001
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All Cause Mortality
All cause mortality ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
17
All Cause Mortality
Adjusted RR (95 CI) 1.34 (1.04 1.71) p0.02
All cause mortality ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
18
Cardiac Mortality
Cardiac mortality ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
19
Cardiac Mortality
Adjusted RR (95 CI) 1.83 (0.99 3.41) p0.06
Cardiac mortality ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
20
Myocardial Infarction gt 28 days
Late myocardial infarction ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
21
Myocardial Infarction gt 28 days
Adjusted RR (95 CI) 1.01 (0.88 1.16) p0.87
Late myocardial infarction ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
22
Definite Stent Thrombosis (patient)
Definite stent thrombosis ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
23
Definite Stent Thrombosis (patient)
Adjusted RR (95 CI) 2.06 (0.77 5.51) p0.15
Definite stent thrombosis ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
24
Definite Stent Thrombosis (lesion)
Definite stent thrombosis ()
Endeavor Cypher
Cypher (n) 5095 4320 3347 2081 751 143 Endeav
or (n) 3090 2338 1339 637 122 0
25
Definite Stent Thrombosis (lesion)
Adjusted RR (95 CI) 1.78 (1.06 3.00) Plt0.05
Definite stent thrombosis ()
Endeavor Cypher
Cypher (n) 5095 4320 3347 2081 751 143 Endeav
or (n) 3090 2338 1339 637 122 0
26
Target Lesion Revascularization (patient)
TLR ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
27
Target Lesion Revascularization (patient)
Adjusted RR (95 CI) 2.25 (1.42 3.56) p0.0005
TLR ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
28
Target Lesion Revascularization (lesion)
TLR ()
Endeavor Cypher
Cypher (n) 5095 4320 3347 2081 751 143 Endeav
or (n) 3090 2338 1339 637 122 0
29
Target Lesion Revascularization (lesion)
Adjusted RR (95 CI) 2.39 (1.82 3.13) Plt0.0001
TLR ()
Endeavor Cypher
Cypher (n) 5095 4320 3347 2081 751 143 Endeav
or (n) 3090 2338 1339 637 122 0
30
In-segment Restenosis (patient)
In-segment restenosis ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
31
In-segment Restenosis (patient)
Adjusted RR (95 CI) 2.25 (1.33 3.81), p0.003
In-segment restenosis ()
Endeavor Cypher
Cypher (n) 3840 3232 2479 1542 555 103 Endeav
or (n) 2282 1725 967 456 92 0
32
In-segment Restenosis (lesion)
In-segment restenosis ()
Endeavor Cypher
Cypher (n) 5095 4320 3347 2081 751 143 Endeav
or (n) 3090 2338 1339 637 122 0
33
In-segment Restenosis (lesion)
Adjusted RR (95 CI) 2.44 (1.76 3.37) Plt0.0001
In-segment restenosis ()
Endeavor Cypher
Cypher (n) 5095 4320 3347 2081 751 143 Endeav
or (n) 3090 2338 1339 637 122 0
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