Large-Scale Registry Examining Safety and Effectiveness of Zotarolimus-

Eluting and Sirolimus-Eluting Stents in Patients with Coronary Artery Disease

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

Western Denmark Heart Registry

Conflicts of interests for Leif Thuesen, M.D.

Cordis, Johnson & Johnson:

Research grants, speaker’s fees.

Medtronic:

Advisory board, research grants, speaker’s fees.

Large-Scale Registry Examining Safety and Effectiveness of Zotarolimus-

Eluting and Sirolimus-Eluting Stents in Patients with Coronary Artery Disease

Background (1)

• 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

The randomized 436-patient ENDEAVOR III trial compared the zotarolimus-eluting Endeavor stent with the sirolimus-eluting Cypher stent

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

Purpose

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

Endpoints

Safety MortalityMyocardial infarction >28 daysStent thrombosis

Effectiveness Clinically driven TLRClinically significant in-segment restenosis

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

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

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

Material and Methods (III)

MI and deathAscertained from national databases

Target lesion revascularization (TLR)Definite stent thrombosisIn-segment restenosis

Obtained from the WDHR by review of all cases of target vessel revascularization occurring during the study period

Registry Study

RegistryInclusion period

August 05 - October 07

PCI centresn=3

Patientsn=6,122

Follow-up 40 - 823 days

SORT-OUT III

RCTInclusion period

January 06 - August 07

PCI centresn=5

Patientsn=2,334

Follow-up270 days

SO III patients in registry

n=1,868 (30.5%)

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

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 ns

Hypertension (%) 49.4 54.1 <0.001

Lipid-lowering therapy (%) 62.6 65.7 <0.05

Previous CABG (%) 8.8 9.4 ns

Previous PCI (%) 32.2 33.7 ns

Previous MI (%) 35.0 36.7 ns

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

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 3.2 <0.001

Lesion type <0.001

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 <0.001

All Cause Mortality

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

All

caus

e m

orta

lity

(%)

EndeavorCypher

All Cause Mortality

Adjusted RR (95% CI) = 1.34 (1.04 – 1.71)

p=0.02A

ll ca

use

mor

talit

y (%

)

EndeavorCypher

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

Cardiac Mortality

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

Car

diac

mor

talit

y (%

)

EndeavorCypher

Cardiac MortalityAdjusted RR (95% CI) = 1.83 (0.99 – 3.41)

p=0.06

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

Car

diac

mor

talit

y (%

)

EndeavorCypher

Myocardial Infarction > 28 days

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

Late

myo

card

ial i

nfar

ctio

n (%

)

EndeavorCypher

Adjusted RR (95% CI) = 1.01 (0.88 – 1.16)

p=0.87

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

Late

myo

card

ial i

nfar

ctio

n (%

)

Myocardial Infarction > 28 days

EndeavorCypher

Definite Stent Thrombosis (patient)

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

Def

inite

ste

nt t

hrom

bosi

s (%

)

EndeavorCypher

Definite Stent Thrombosis (patient)Adjusted RR (95% CI) = 2.06 (0.77 – 5.51)

p=0.15D

efin

ite s

tent

thr

ombo

sis

(%)

EndeavorCypher

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

Definite Stent Thrombosis (lesion)

Cypher (n) 5095 4320 3347 2081 751 143Endeavor (n) 3090 2338 1339 637 122 0

Def

inite

ste

nt t

hrom

bosi

s (%

)

EndeavorCypher

Definite Stent Thrombosis (lesion)Adjusted RR (95% CI) = 1.78 (1.06 – 3.00)

P<0.05

Cypher (n) 5095 4320 3347 2081 751 143Endeavor (n) 3090 2338 1339 637 122 0

Def

inite

ste

nt t

hrom

bosi

s (%

)

EndeavorCypher

Target Lesion Revascularization (patient)

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

TLR

(%

)

EndeavorCypher

Target Lesion Revascularization (patient)Adjusted RR (95% CI) = 2.25 (1.42 – 3.56)

p=0.0005

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

TLR

(%

)

EndeavorCypher

Target Lesion Revascularization (lesion)

Cypher (n) 5095 4320 3347 2081 751 143Endeavor (n) 3090 2338 1339 637 122 0

TLR

(%

)

EndeavorCypher

Target Lesion Revascularization (lesion)Adjusted RR (95% CI) = 2.39 (1.82 – 3.13)

P<0.0001

Cypher (n) 5095 4320 3347 2081 751 143Endeavor (n) 3090 2338 1339 637 122 0

TLR

(%

)

EndeavorCypher

In-segment Restenosis (patient)

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

In-s

egm

ent

rest

enos

is (

%)

EndeavorCypher

In-segment Restenosis (patient)Adjusted RR (95% CI) = 2.25 (1.33 – 3.81), p=0.003

Cypher (n) 3840 3232 2479 1542 555 103Endeavor (n) 2282 1725 967 456 92 0

In-s

egm

ent

rest

enos

is (

%)

EndeavorCypher

In-segment Restenosis (lesion)

Cypher (n) 5095 4320 3347 2081 751 143Endeavor (n) 3090 2338 1339 637 122 0

In-s

egm

ent

rest

enos

is (

%)

EndeavorCypher

In-segment Restenosis (lesion)Adjusted RR (95% CI) = 2.44 (1.76 – 3.37)

P<0.0001

Cypher (n) 5095 4320 3347 2081 751 143Endeavor (n) 3090 2338 1339 637 122 0

In-s

egm

ent

rest

enos

is (

%)

EndeavorCypher

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.

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