Shift of a General Idea with the Introduction of DESTCT, Oct 2002 Cardiovascular Research Foundation ANGIOPLASTY SUMMIT TLR vs. Stent Length SIRIUS : Sirolimus Eluting Stent % 10.2

Cardiovascular Research Foundation ANGIOPLASTY SUMMIT

PCI for Long Coronary Lesion

Shift of a General Idea with the Introduction of DES

In the Bare Metal Stent Era

In the Bare Metal Stent Era


Higher Restenosis Rate With Increasing Stent Length and Decreasing Stent Area

0

0.2

0.4

0.6

35

60

7.5 1012.04.0

Restenosis

Minimum in-stent area

Stent Length

De Feyter. Circulation 1999; 100:1777-83


Spot Stenting vs. Long StentSpot Stenting vs. Long Stent

Spot stenting Long stenting

0

5

10

15

20

25

30

35

40

38 %

22 % 25 %

39 %

P<0.05 P<0.05

6 Months MACE6 Months MACE Restenosis Restenosis RateRate

Colombo A et al, J Am Coll Cardiol 2001;38:1427-33


Single Stent vs. Multiple StentSingle Stent vs. Multiple StentRestenosis Rate

0

10

20

30

40

38.5 37.5

P = NS

%

One stent (n=62)

Two stents (n=62)

Hoffmann R, et al. Am J Cardiol 2002:90:460-464


Single Stent vs. Multiple StentSingle Stent vs. Multiple Stent

Hoffmann R, et al. Am J Cardiol 2002:90:460-464

150

160

170

180

190

One stent Two stent1500

1700

1900

2100

2300

2500ml Euros

165

190

1577

2293

P = 0.056 P < 0.001

Contrast agentCost-Effectiveness

Intervention Cost


Stenting with Bare Metal Stent for Long Coronary Lesion

It was suggested that…

• Spot stenting

• Single stent


What is changing ?

In the Era of Drug Eluting Stent


No Increase of Restenosis with Increasing SES length

SIRIUS : Sirolimus Eluting Stent%

23.529.7

36.744.3

52.4

1 1.7 2.6 4.1 6.50

10

20

30

40

50

60

ControlSirolimus

88 1616 32322424 4040

%

Stent Length (mm) TCT, Oct 2002


TLR vs. Stent LengthSIRIUS : Sirolimus Eluting Stent

%

10.2 13.216.9

21.426.6

2.3 3 3.3 5 6.40

10

20

30

40

50

60

ControlSirolimus

88 1616 32322424 4040

%

Stent Length (mm) TCT, Sep 2003


Relative Reduction of RestenosisSIRIUS : Sirolimus Eluting Stent

74.8 %76.6 %77.6 %< 2.5mm77.9 %79.2 %79.8 %2.5 – 3.0 mm80.4 %81.2 %81.7 %> 3.0mm≥ 15mm12 – 15 mm< 12mm

NonNon--diabeticdiabetic Lesion lengthLesion length

Ref Ref DiaDia

< 2.5mm2.5 – 3.0 mm> 3.0mm

69.6 %74.1 %78.0 %< 12mm

67.8 %72.7 %77.0 %

12 – 15 mm

64.5 %70.2 %75.3 %≥ 15mm

DiabeticDiabetic

Ref Ref DiaDia

TCT, Oct 2002


Restenosis in Lesions ≥ 10mmin stented segment

TAXUS II : Paclitaxel Eluting Stent

%

0

5

10

15

20

25

20.6

0.8

P < 0.001

Combined control(n=144)

Combined TAXUS (n=133) Grube E, ACC, 2003


18.9

25.8

41.5

5.6 7.2

14.9

0

10

20

30

40

50

<10 mm 10 - 20 mm >20 mm

Res

teno

sis

Control (n=652) TAXUS (n=662)

P=0.01

P=0.004

P<0.0001

RestenosisRestenosis (analysis segment)(analysis segment)

Lesion length (mm)Lesion length (mm)

N=90 N=90 N=124 N=153 N=53 N=47

Impact of Lesion Length in TAXUS IV


Full Metal Jacket in DES71 patients (153 lesion, 209 SES)

Lesion length : 52.1±23.1mm

• Reference vessel diameter: 2.59±0.58mm• Stented segment : 83.6±23.9mm•Glycoprotein IIb/IIIa inhibitors: 65%

Orlic D, ACC, 2004


Full Metal Jacket in DES

1(1.4%)Death due to MI6-month follow-up

7.2%TLR

1(1.4%)Subacute stent thrombosis30 days outcomes

15(21.1%)Non Q-MI (CK-MB>3 normal)1(1.4%)Q-MI

In-hospital events (postprocedure)

Sirolimus(n=71)

Orlic D, ACC, 2004


RESEARCH registryStented length > 36 mm (de novo lesion)

2.7 ± 0.9 (2-6)Stents per lesion

67 patients (71%)6-month angiography

62 ± 21mm(41-134 mm)Stented length

96 pts( 102 lesions) Study population

Binary restenosis (DS > 50% ) : 11.9%Serruys PW ACC, 2004


6-month Angiographic Follow-UpRESEARCH registry

-0.160.130.02Late lumen loss192717% diameter stenosis

2.122.042.74Minimal lumen diameter2.632.823.30Reference vsl diameter

Distal In-stentProximal

In-lesion binary restenosis : 11.9%

Serruys PW ACC, 2004


Clinical Follow-Up at 320 DaysRESEARCH registry

0

5

10

2%

0%

%

Death TLRMI MACE

5%

7%

Serruys PW ACC, 2004


Comparison of Late LossStented length (mm)

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.411.33

Kobayashi

1.20

-angio guided

-IVUS guided

ULSE-1 stent

PULSE-2 stent

ADVANCE

RESEARCH

1.18 1.14

0.79

0.13

Lat

e lo

ss (m

m)

52 35 42 32 33 62

TulipTulip IM

P IM Serruys PW ACC, 2004

“Long Cypher”Multicenter Prospective non-

Randomized Registry study forDES in Very Long Lesion ;

-Preliminary Data-• Coordinating center : Asan Medical Center,

• Collaborating centers Ajou University Medical Center, Catholic University of Korea, St Mary’s Hospital, Chonnam Nat’l University Hospital, Keimyung University Dongsan Medical Center, Korea University Kuro Hospital, Samsung Medical Center, Seoul National University Hospital, Yonsei University Severance Hospital, Yonsei University Wonju Christian Hospital,

SJ Park

SJ TahkKB SeungMH Jeong

KS KimDJ Oh

HC GwonLee MM, Koo BK

YS JangJH Yoon


“Long Cypher”Prospective, Non-randomized

Multicenter, Registry Study in Korea

“Long Cypher”Prospective, Non-randomized

Multicenter, Registry Study in Korea

From March 2003 - February 2004De-novo Lesions

(≥ 24mm)487 patients, 597 lesions

Cypher stent (≥ 28mm)

BMS stent (≥ 28mm)

149 patients, 173 lesionsMean stent length : 37mm

(28 – 73 mm)

338 patients, 424 lesionsMean stent length : 41mm

(28- 92 mm)


Lesion Characteristics“Long Cypher”

0.01229.9 ± 12.733.0 ± 13.1Lesion length (mm)

0.89874.0 ± 16.774.2 ± 16.3Diameter stenosis (%)

0.1460.78 ± 0.520.72 ± 0.46MLD (mm)

<0.0012.81 ± 0.592.63 ± 0.47Distal reference (mm)

<0.0013.27 ± 0.553.02 ± 0.46Proximal reference (mm)

P valueControl

(n=173)

Cypher

(n=424)


“Long Cypher”Stenting Procedure

<0.0011.06 ± 0.141.11 ± 0.16Balloon-to-artery ratio

<0.00144 (25%)196 (46%)Overlapping0.00136.6 ± 12.440.8 ± 15.0Contiguous stent length (mm)

<0.0011.29 ± 0.541.55 ± 0.68Used No of stents

0.4927 (4%)11 (3%)Use of Abciximab<0.00171 (41%)303 (72%)IVUS guidance

0.0083.41 ± 0.513.31 ± 0.38Maximal balloon size

<0.00111.7 ± 3.315.4 ± 3.6Maximal inflation pressure (atm)

P valueControl(n=173)

Cypher(n=424)


“Long Cypher”

Post-Procedure QCA Analysis

<0.0013.33 ± 0.553.09 ± 0.49Proximal reference (mm)

0.0222.13 ± 0.682.00 ± 0.61Acute gain

0.0625.3 ± 14.42.7 ± 14.9Diameter stenosis (%)

<0.0012.92 ± 0.542.72 ± 0.43MLD (mm)

<0.0012.85 ± 0.522.56 ± 0.45Distal reference (mm)

P valueControl

(n=173)

Cypher

(n=424)


AngiographicallyAngiographically normal reference vessels normal reference vessels actually had 28 actually had 28 -- 38% plaque burden when 38% plaque burden when seen by IVUSseen by IVUS

37.9 ± 10.6Plaque burden (%)

27.9 ± 6.7Plaque burden (%)

9.4 ± 3.3EEM CSA (mm2)

15.4 ± 3.6EEM CSA (mm2)9.6 ± 3.0Lumen CSA (mm2)

Proximal reference (mm2)

6.8 ± 2.5Lumen CSA (mm2)

Distal reference

67N


Postprocedural Stent CSA

67N

6.8 ± 2.5Stent CSA9.4 ± 3.3EEM CSA

Stent (mm2)


“Long Cypher”In-Hospital Outcomes

1.00000Stent thrmbosis

1.00000TVR

18 (12%)29 (9%)Non-Q wave ***00Q wave

1.0001 (0.7%) **0Death0.05194.8%97.8%Procedural success *

1.00000TLR

0.22818 (12%)29 (9%)MI

P value

Control(n=149)

Cypher(n=338)

* Final TIMI flow ≥ 2 and residual diameter stenosis ≤ 30%** No reflow after multivessel PCI *** CK-MB ≥ 3 times normal value


“Long Cypher”30-Day Outcomes

1.00000Sent thrombosis

1.00000TVR

00Non-Q wave00Q wave

0.5191 (0.7%)1 (0.3%) *Death

1.00000TLR

1.00000MI1 (0.7%)0Cardiac

01 (0.3%)Non-cardiac

P value

Control(n=149)

Cypher(n=338)

* Due to intracranial hemorrhage, 5 days after intervention


“Long Cypher”6-Month Outcomes

1.00000Stent thrombosis

160Repeat PCI21CABG

<0.00119 (15.0%)2 (1.1%)MACE

00Non-Q wave00Q wave

1.0001 (0.8%)1 (0.6%) Death

<0.00118 (14.2%)1 (0.6%)TLR

1.00000MI1 (0.8%)0Cardiac

01 (0.6%)Non-cardiac


Cypher(n=162)


6-Month QCA Analysis“Long Cypher”

<0.001<0.00142 (43.3%)42 (43.3%)3 (2.6%)3 (2.6%)Restenosis Restenosis

0.1720.1723.64 3.64 ±± 0.450.453.00 3.00 ±± 0.490.49Proximal reference(mm)Proximal reference(mm)

<0.001<0.0011.45 1.45 ±± 0.720.720.31 0.31 ±± 0.570.57Late loss (mm)Late loss (mm)<0.001<0.00148.0 48.0 ±± 22.222.29.3 9.3 ±± 17.417.4Diameter Diameter stenosisstenosis (%)(%)<0.001<0.0011.53 1.53 ±± 0.760.762.54 2.54 ±± 0.530.53MLD (mm)MLD (mm)0.2410.2412.69 2.69 ±± 0.580.582.60 2.60 ±± 0.430.43Distal reference (mm)Distal reference (mm)

P valueP valueControlControl(n=97)(n=97)

CypherCypher(n=117)(n=117)


Late LossLate Loss“Long Cypher”

0.44

1.46

0.18 0.140.31

1.45

0.04 0.09

0.0

0.5

1.0

1.5

2.0

In-segment Proximal edge In-stent Distal edge

SES (n=110) BMS (n=79)

P=0.334

P<0.001

P=0.417

mm

P<0.001


Restenosis RateRestenosis Rate“Long Cypher”

2.6

43.3

07.2

2.6

42.3

0

10.3

0

10

20

30

40

50


SES (n=110) BMS (n=79)

P<0.001 P<0.001

P=0.002P=0.002

%


Pattern of 3 Restenotic Cases“Long Cypher”

Pattern of 3 Restenotic Cases

100

26.2

0

54.8

0 11.90 7.10

20

40

60

80

100

Focal Diffuse Proliferative Total

SES (n=3) BMS (n=42)%

LAD 23 x 18, Focal, distal instent 54%LCX 28 x 23, Focal, distal instent 56%RCA, 33 x 23, Focal, overlapping area 82%

Why not stent-overlap ?

Why not stent-overlap ?

Multiple Stent vs. Single Stent


Impact of Stent OverlappingSIRIUS : Sirolimus Eluting Stent

<0.00142.78.8In-segment<0.00142.77.1In-stent

Restenosis (%)<0.0010.930.20In-segment<0.0011.140.23In-stent

Late loss (mm)


Sirolimus(n=176)

TCT, Oct 2002


Restenosis in > 1 Stent in stented segment

TAXUS II : Paclitaxel Eluting Stent%

0

5

10

15

20

25

21.1

0.0

P = 0.128

Combined control(n=19)

Combined TAXUS (n=14)

Grube E, ACC, 2003


25.6

46.2

8.3

00

10

20

30

40

50

60

Single stent Multiple stents

Res

teno

sis

Control (n=267) TAXUS (n=291)

Impact of Multiple StentsImpact of Multiple Stents

P<0.0001 P=0.005

RestenosisRestenosis (analysis segment)(analysis segment)

N=253 N=276 N=13N=15

TAXUS IV


Restenosis Rate According to Multiple Stenting

Restenosis Rate According to Multiple Stenting

5.3

54.2

0

39.7

0

10

20

30

40

50

60

Multiple stent Single stent

SES BMS

P<0.001 P<0.001

%

N 57 24 60 73

“Long Cypher”


Restenosis Rate According to RestenosisStent Overlap

Rate According to Stent Overlap

1.8

35.0

3.6

50.0

0

10

20

30

40

50

Overlap site Non-overlap site

SES (n=56) BMS (n=20)

P<0.001P<0.001

%

“Long Cypher”


Area Change of Overlap Site“Long Cypher”

12.93 13.55

6.878.25

6.075.30

0

5

10

15

EEM P+M Lumen

Post-intervention Follow-Up

P<0.001

mm2

P<0.001

P<0.001

Total 29 available lesions


StentStent--overlap did not show any differenceoverlap did not show any difference

0.66 0.731.55 1.65

-0.82 -0.99

-2.0-1.5-1.0-0.50.00.51.01.52.0

EEM P+M Lumen

Worst site in non-overlapWorst site in overlapmm2

Area changes at 6 months F/U Area changes at 6 months F/U

P=0.608

P=0.361P=0.689

“Long Cypher”


Shift of an Idea for Long Lesion with DES

“ the longer, the better ”

• Full lesion coverage

• Acceptance of stent-overlap

In SubgroupsIn Subgroups

Does it applied to all patients and lesion subsets ?


“Long Cypher”

Restenosis Rate in DMRestenosis Rate in DM

3.3

54.8

0 6.5 3.3

54.8

09.7

0

10

20

30

40

50

60


SES (n=30) BMS (n=31)

P<0.001 P<0.001P=0.238

P=0.492

%


“Long Cypher”

Restenosis Rate in LADRestenosis Rate in LAD

1.4

38.5

0

10.3

1.4

38.5

0

10.3

0

10

20

30

40


SES (n=73) BMS (n=39)

P<0.001 P<0.001P=0.013P=0.013

%


Restenosis Rate in Acute Coronary SyndromeRestenosis Rate in Acute Coronary Syndrome

1.8

40

06.7

1.8

37.8

06.7

0

10

20

30

40


SES (n=55) BMS (n=45)

P<0.001 P<0.001

P=0.088P=0.088

%

“Long Cypher”


Restenosis Rate in Small Vessel (<3.0mm)Restenosis Rate in Small Vessel (<3.0mm)

“Long Cypher”

3.9

59

010

3.9

54

0

14

0

10

20

30

40

50

60


SES (n=76) BMS (n=50)

P<0.001 P<0.001

P=0.001P=0.009

%


Restenosis Rate According to Reference DiameterRestenosis Rate According to Reference Diameter

3.9

54

0

37

0

25

0

10

20

30

40

50

60

<3.0 3.0-3.5 >3.5

SES BMS

P<0.001

P<0.001

%

P=0.544

“Long Cypher”

N 76 50 36 27 4 20


Overall

Male

Female

Diabetes

No Diabetes

LAD

Non-LAD

Small Vessel (<2.75)

Large Vessel

Non ACS

Overlap

No Overlap

1.00.90.80.70.60.50.40.30.20.10 00.9

Angiographic RestenosisSES BMS P-value

Sirolimus betterSirolimus better

ACS

<0.0001

<0.0001

<0.0001

<0.0001<0.0001

<0.0001

<0.0001<0.0001

<0.0001

2.7 46.8 <0.0001

2.8 47.0

4.3 46.2 0.0120

3.4 60.0 0.0001

2.5 40.7

1.5 43.3

4.8 49.0

2.9 72.0

2.7 35.2

2.0 42.5 0.0001

3.4 51.3

5.4 55.0

0 44.1

Hazards Ratio 95% CI 0.8 .7

Shift of a General Idea with the Introduction of DESTCT, Oct 2002 Cardiovascular Research Foundation ANGIOPLASTY SUMMIT TLR vs. Stent Length SIRIUS : Sirolimus Eluting Stent % 10.2

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