1 contemporary pci with the cypher ® stent: the standard of care and comparison david e. kandzari,...

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Contemporary PCI with the CYPHERContemporary PCI with the CYPHER®® Stent: Stent:

The Standard of Care and ComparisonThe Standard of Care and Comparison

David E. Kandzari, MD, FACC, FSCAIDavid E. Kandzari, MD, FACC, FSCAIChief Medical OfficerChief Medical OfficerCordis CorporationCordis Corporation

[email protected]@crdus.jnj.com

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DisclosureDisclosure

Employee:Employee: Cordis, Cordis, Johnson Johnson && Johnson Johnson

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Dedicated Trials with CYPHER® Stent in Specific Patient/Lesion Types

Single, De Novo

LongLesions

SmallVessels

DM

MVD

ISR

CTO

Bifurcations

AMI

LeftMain

DirectStenting

Stairway to Evidence-Based Medicine

RAVEL, SIRIUS, REALITY, ENDEAVOR III

DIRECT

TYPHOONSTRATEGYSESAMIMISSIONPROSIT

Park LLPark LL 2

SVELTE,SIRIUS 2.25SES-SMARTPache, et al.ISAR-SMART 3

PORTO IDECODESCORPIUSDIABETES, CARDIA*ISAR-DIABETES

ACROSS*PRISON II

TROPICALSISRRIBS IIISAR-DESIRE

ARTS-2

COMBAT*

SIRIUS-BIFNordic PCI

Differing Complexity

* Trials have not been presented/published

Randomized Controlled Trial (RCT) vs. BMS, Brachytherapy, or POBANON-RCTRCTs VS. DES

SIRTAX, BASKET, a

nd TAXi (All-C

omers), Zhang, e

t al.

E-SIRIUS,

C-SIRIUS

SCANDSTENT, CORPAL, C

ervinka, et a

l. (high-ris

k)SVG

RRISC

16 RCTs:SES vs. BMS

N=5,535

13 RCTs SES vs. PES

n = 7,917

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RAVEL*RAVEL* SIRIUS*SIRIUS* C-SIRIUSC-SIRIUS E-SIRIUSE-SIRIUS

Study TypeStudy Type Prospective, Multi-Center, Blinded, RandomizedProspective, Multi-Center, Blinded, Randomized

# of Patients# of Patients238238

(120 CYPHER(120 CYPHER®®, , 118 BMS)118 BMS)

1,0581,058(533 CYPHER(533 CYPHER®®, ,

525 BMS)525 BMS)

100100(50 CYPHER(50 CYPHER®®, ,

50 BMS)50 BMS)

352352(175 CYPHER(175 CYPHER®®, ,

177 BMS)177 BMS)

Lesion TypeLesion Type SingleSingle de novo de novo lesion in native coronary artery lesion in native coronary artery

RVDRVD 2.5 to 2.5 to 3.5 mm3.5 mm 2.5 to 2.5 to 3.0 mm3.0 mm

Lesion LengthLesion LengthLesion had to be Lesion had to be covered with a covered with a single 18 mm single 18 mm

stentstent

15 to 30 mm in 15 to 30 mm in length coverable length coverable

with 2 stentswith 2 stents15 to 32 mm in length 15 to 32 mm in length coverable with 2 stentscoverable with 2 stents

AspirinAspirin Indefinitely Indefinitely

Clopidogrel or Clopidogrel or TiclopidineTiclopidine 2 months2 months 3 months3 months 2 months2 months 2 months2 months

Compliance to Compliance to 4-year follow-up4-year follow-up

CYPHERCYPHER®® – 94.2% – 94.2%BMS – 94.1%BMS – 94.1%




Patient-level Pooled Analysis of 4 RCTsPatient-level Pooled Analysis of 4 RCTs

*The 2 trials provided to support US indication: Improving coronary lumen diameter in patients with symptomatic ischemic disease due to discrete de novo lesions of ≤ 30 mm with a diameter of ≥ 2.5mm or ≤ 3.5mm.

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Freedom From TLR Through 4 YearsFreedom From TLR Through 4 YearsF

reed

om

Fro

m T

LR

Fre

edo

m F

rom

TL

R

Time After Initial Procedure (days)Time After Initial Procedure (days)

Pooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS TrialsPooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials

LR p<0.001LR p<0.001

= 15.7%= 15.7%

®

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Cumulative Incidence of Myocardial Cumulative Incidence of Myocardial Infarction*: 0 – 1,440 Days (4 Years)Infarction*: 0 – 1,440 Days (4 Years)

# Entered# Entered 0 D0 D 180 D180 D 360 D (1 yr)360 D (1 yr) 720 D (2 yr)720 D (2 yr) 1080 D (3 yr)1080 D (3 yr) 1440 D (4 yr)1440 D (4 yr)

SirolimusSirolimus 878878 847847 832832 807807 779779 741741

Bx VELOCITY®Bx VELOCITY® 870870 837837 824824 806806 782782 740740

6.2%6.2%

LR p=0.8672LR p=0.8672 (95% CI 0.2%[-2.2%, 2.6%]) (95% CI 0.2%[-2.2%, 2.6%])

Cu

mu

lati

ve I

nci

de

nce

of

MI

Cu

mu

lati

ve I

nci

de

nce

of

MI


6.4%6.4%

Pooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS TrialsPooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials* Non –Q wave CK levels greater then 2 times normal with elevated CKMB* Non –Q wave CK levels greater then 2 times normal with elevated CKMB

®

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Cumulative Incidence of Death: Cumulative Incidence of Death: 0 – 1,440 Days (4 Years)0 – 1,440 Days (4 Years)

# Entered# Entered 0 D0 D 180 D180 D 360 D (1 yr)360 D (1 yr) 720 D (2 yr)720 D (2 yr) 1080 D (3 yr)1080 D (3 yr) 1440 D (4 yr)1440 D (4 yr)

SirolimusSirolimus 878878 870870 863863 842842 817817 776776

Bx VELOCITY®Bx VELOCITY® 870870 863863 857857 843843 824824 781781

LR p=0.2355LR p=0.2355

(95% CI 1.4%[-1.0%, 3.7%]) (95% CI 1.4%[-1.0%, 3.7%])

Pooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS TrialsPooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials

Cu

mu

lati

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of

Dea

thC

um

ula

tive

In

cid

en

ce o

f D

eath


6.7%6.7%

5.4%5.4%

®

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Cumulative Incidence of Stent Thrombosis Cumulative Incidence of Stent Thrombosis to Latest Follow-up (4-5 Years, 4 Trials)to Latest Follow-up (4-5 Years, 4 Trials)

SESSES

1.2%1.2%

BMSBMS

0.6%0.6%

pp-Value-Value

0.2160.216

Pooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS TrialsPooled Data from RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS TrialsData between 4 and 5 years are from the RAVEL and SIRIUS TrialsData between 4 and 5 years are from the RAVEL and SIRIUS Trials

ProtocolProtocol

BMSBMSSESSES

SESSES

1.7%1.7%

BMSBMS

1.9%1.9%

pp-Value-Value

0.7030.703

SESSES

4.1%4.1%

BMSBMS

5.1%5.1%

pp-Value-Value

0.7950.795Definite or Definite or Probable ARCProbable ARC

Any ARCAny ARC

SESSES

1.4%1.4%

BMSBMS

1.0%1.0%

pp-Value-Value

0.4960.496Definite ARCDefinite ARC

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Clinical Impact Following TLR and Clinical Impact Following TLR and ARC (Definite/Probable) STARC (Definite/Probable) ST

CYPHERCYPHER®® Stent Stentn = 878n = 878

BMSBMSn = 870n = 870

4 Deaths4 Deaths13 MI13 MI

13 D/MI13 D/MI

7714141717

13 ST13 ST

Deaths (n)Deaths (n)MI (n)MI (n)D/MI (n)D/MI (n)


15 D/MI15 D/MI


13 D/MI13 D/MI

194 TLRs194 TLRs 15 ST15 ST

101022222828

Deaths (n)Deaths (n)MI (n)MI (n)D/MI (n)D/MI (n)

3 C3 C2 NC2 NC

8 C8 C2 NC2 NC

5 C5 C2 NC2 NC

Cardiac Death = CCardiac Death = CNon-Cardiac Death = NCNon-Cardiac Death = NC

4-year Follow-up of 4 Key RCTs4-year Follow-up of 4 Key RCTs


4 D/MI4 D/MI

56 TLRs56 TLRs1 C1 C2 NC2 NC

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Meta-Analysis: Any MI up to 1 Year in Meta-Analysis: Any MI up to 1 Year in SES vs. BMS RCTsSES vs. BMS RCTs

1 / 1201 / 120 2 / 1182 / 118

16 / 53316 / 533 18 / 52518 / 525

8 / 1758 / 175 4 / 1774 / 177

1 / 501 / 50 2 / 502 / 50

1 / 541 / 54 2 / 292 / 29

2 / 1292 / 129 10 / 12810 / 128

6 / 2646 / 264 12 / 28112 / 281

2 / 1622 / 162 5 / 1575 / 157

2 / 802 / 80 6 / 806 / 80

2 / 1002 / 100 3 / 1003 / 100

9 / 2509 / 250 7 / 2507 / 250

6 / 876 / 87 8 / 888 / 88

4 / 3554 / 355 5 / 3575 / 357

0 / 1600 / 160 0 / 1600 / 160

4 / 954 / 95 5 / 955 / 95

9 / 1509 / 150 15 / 15815 / 158

4.324.32

19.2119.21

6.396.39

1.821.82

1.371.37

4.674.67

9.889.88

5.795.79

2.902.90

3.633.63

9.089.08

3.183.18

12.9312.93

5.815.81

3.453.45

5.595.59

7.177.17

11.8411.84

4.214.21

1.421.42

0.650.65

2.382.38

6.626.62

5.675.67

1.401.40

3.283.28

6.186.18

0.990.99

17.8317.83

26.8626.86

1.721.72

1.781.78

Study nameStudy name ModelModel

MH risk MH risk differencedifference pp-Value-Value SESSES BMSBMS

Relative Relative Weight (Fixed)Weight (Fixed)

Relative Relative Weight RandomWeight Random

MH risk difference and 95% CIMH risk difference and 95% CI

RAVELRAVEL

SIRIUSSIRIUS

E-SIRIUSE-SIRIUS

C-SIRIUSC-SIRIUS

DECODEDECODE

SES-SMARTSES-SMART

BASKETBASKET

SCANDSTENTSCANDSTENT

DIABETESDIABETES

PRISON IIPRISON II

PachePache

STRATEGYSTRATEGY

TYPHOONTYPHOON

SESAMISESAMI

SCORPIUSSCORPIUS

MISSIONMISSION

-0.0086-0.0086

-0.0043-0.0043

0.02310.0231

-0.0200-0.0200

-0.0504-0.0504

-0.0626-0.0626

-0.0200-0.0200

-0.0195-0.0195

-0.0500-0.0500

-0.0100-0.0100

0.00800.0080

-0.0219-0.0219

-0.0027-0.0027

0.00000.0000

-0.0105-0.0105

-0.0349-0.0349

-0.0112-0.0112

-0.0067-0.0067

0.5520.552

0.6940.694

0.2320.232

0.5570.557

0.3180.318

0.0160.016

0.1870.187

0.2370.237

0.1440.144

0.6500.650

0.6110.611

0.5920.592

0.7440.744

1.0001.000

0.7330.733

0.2490.249

0.0180.018

0.1010.101FixedFixed

RandomRandom

Favors SESFavors SES Favors BMSFavors BMS

-0.15-0.15 -0.08-0.08 0.000.00 0.080.08 0.150.15

Q-ValueQ-Value Degree of freedom (Q) Degree of freedom (Q) II22 p-p-ValueValue

Heterogeneity Heterogeneity 16.514 16.514 15 15 9.1699.169 0.34870.3487

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Q-ValueQ-Value Degree of freedom (Q) Degree of freedom (Q) II22 p-p-Value Value

Heterogeneity Heterogeneity 6.614 6.614 15 15 0.0000.000 0.9675 0.9675

Meta-Analysis: All Cause Mortality up to Meta-Analysis: All Cause Mortality up to 1 Year in SES vs. BMS RCTs1 Year in SES vs. BMS RCTs





RAVELRAVEL

SIRIUSSIRIUS

E-SIRIUSE-SIRIUS

C-SIRIUSC-SIRIUS

DECODEDECODE

SES-SMARTSES-SMART

BASKETBASKET


DIABETESDIABETES

PRISON IIPRISON II

PachePache

STRATEGYSTRATEGY

TYPHOONTYPHOON

SESAMISESAMI

SCORPIUSSCORPIUS

MISSIONMISSION

2 / 1202 / 1202 / 1182 / 118

7 / 5337 / 5334 / 5254 / 525

2 / 1752 / 1751 / 1771 / 177

0 / 500 / 50 0 / 500 / 50

0 / 540 / 54 2 / 292 / 29

0 / 1290 / 1292 / 1282 / 128

5 / 2645 / 2649 / 2819 / 281

1 / 1621 / 1621 / 1571 / 157

0 / 800 / 80 0 / 800 / 80

0 / 1000 / 1000 / 1000 / 100

7 / 2057 / 2055 / 2045 / 204

7 / 877 / 87 8 / 888 / 88

8 / 3558 / 3558 / 3578 / 357

0 / 1600 / 1600 / 1600 / 160

5 / 955 / 95 4 / 954 / 95

2 / 1502 / 1504 / 1584 / 158

4.394.39

19.5319.53

6.506.50

1.851.85

1.391.39

4.744.74

10.0510.05

5.895.89

2.952.95

3.693.69

7.557.55

3.233.23

13.1413.14

5.915.91

3.513.51

5.685.68

2.832.83

20.3320.33

8.178.17

2.072.07

0.290.29

4.454.45

4.364.36

10.0710.07

5.205.20

8.078.07

2.832.83

0.440.44

6.386.38

20.4620.46

0.830.83

3.233.23

FixedFixed

RandomRandom

-0.0003-0.0003

0.00550.0055

0.00580.0058

0.00000.0000

-0.0690-0.0690

-0.0156-0.0156

-0.0131-0.0131

-0.0002-0.0002

0.00000.0000

0.00000.0000

0.00960.0096

-0.0104-0.0104

0.00010.0001

0.00000.0000

0.01050.0105

-0.0120-0.0120

-0.0015-0.0015

0.00000.0000

0.9860.986

0.3760.376

0.5560.556

1.0001.000

0.1850.185

0.2400.240

0.3300.330

0.9820.982

1.0001.000

1.0001.000

0.5630.563

0.8050.805

0.9910.991

1.0001.000

0.7330.733

0.4430.443

0.6850.685

0.9900.990



-0.15-0.15 -0.08-0.08 0.000.00 0.080.08 0.150.15

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Meta-Analysis: Thrombosis up to 1 Year in Meta-Analysis: Thrombosis up to 1 Year in SES vs. BMS RCTsSES vs. BMS RCTs






0 / 1200 / 120 0 / 1180 / 118

2 / 5332 / 533 4 / 5254 / 525

2 / 1752 / 175 0 / 1770 / 177

1 / 501 / 50 1 / 501 / 50

0 / 540 / 54 0 / 290 / 29

1 / 1291 / 129 4 / 1284 / 128

3 / 2643 / 264 2 / 2812 / 281

1 / 1621 / 162 5 / 1575 / 157

0 / 800 / 80 2 / 802 / 80

2 / 1002 / 100 0 / 1000 / 100

3 / 2503 / 250 2 / 2502 / 250

0 / 870 / 87 2 / 882 / 88

12 / 35512 / 35513 / 35713 / 357

5 / 1605 / 160 6 / 1606 / 160

2 / 1502 / 150 3 / 1583 / 158

4.474.47

19.8919.89

6.626.62

1.881.88

1.421.42

4.834.83

10.2410.24

6.006.00

3.013.01

3.763.76

9.409.40

3.293.29

13.3913.39

6.026.02

5.795.79

11.0911.09

35.8335.83

8.058.05

0.980.98

1.081.08

2.592.59

11.3311.33

3.283.28

1.721.72

2.672.67

9.699.69

2.072.07

4.034.03

1.851.85

3.733.73

-0.15-0.15 -0.08-0.08 0.000.00 0.080.08 0.150.15

RAVELRAVEL

SIRIUSSIRIUS

E-SIRIUSE-SIRIUS

C-SIRIUSC-SIRIUS

DECODEDECODE

SES-SMARTSES-SMART

BASKETBASKET


DIABETESDIABETES

PRISON IIPRISON II

PachePache

STRATEGYSTRATEGY

TYPHOONTYPHOON

SESAMISESAMI

MISSIONMISSION

0.00000.0000

-0.0039-0.0039

0.01140.0114

0.00000.0000

0.00000.0000

-0.0235-0.0235

0.00420.0042

-0.0257-0.0257

-0.0250-0.0250

0.02000.0200

0.00400.0040

-0.0227-0.0227

-0.0026-0.0026

-0.0063-0.0063

-0.0057-0.0057

-0.0037-0.0037

-0.0018-0.0018

1.0001.000

0.4030.403

0.2420.242

1.0001.000

1.0001.000

0.1720.172

0.6060.606

0.0930.093

0.2360.236

0.2380.238

0.6530.653

0.2380.238

0.8500.850

0.7590.759

0.6930.693

0.2810.281

0.5050.505FixedFixed

RandomRandom


Q-ValueQ-Value Degree of freedom (Q) Degree of freedom (Q) II22 p-p-ValueValue

Heterogeneity Heterogeneity 11.681 11.681 1414 0.000 0.000 0.6319 0.6319

14

0

10

20

30

40

50

0

10

20

30

40

50

TLR in Randomized Clinical Trials of TLR in Randomized Clinical Trials of CYPHERCYPHER StentStent vs. BMS Control vs. BMS Control

n= n= 878 878 870 870 100 100 100 100 129 129 128 128 80 80 80 80 54 54 29 29 95 95 95 95 355 355 355 355 160 160 160 160 87 87 88 88 150 150 158 158

(%)

Pat

ien

ts(%

) P

atie

nts

PRISON 2PRISON 2SES-SES-

SMARTSMART

1 year1 yearp=0.001p=0.001

79%79%

8 months8 monthsp=0.002p=0.002

67%67%

1 year1 yearp<0.0001p<0.0001

79%79%

9 months9 monthsp<0.001p<0.001

80%80%(TVR)(TVR)

DIABETESDIABETES DECODEDECODE SCORPIUSSCORPIUS1 year1 year

p=0.043p=0.043

62%62%

8 months8 monthsp=0.002p=0.002

75%75%

TYPHOONTYPHOON SESAMISESAMI1 year1 year

p<0.0001p<0.0001

71%71%

1 year1 yearp<0.05p<0.05

62%62%

STRATEGYSTRATEGY8 months8 monthsp=0.006p=0.006

72%72%

MISSIONMISSION1 year1 year

p=0.005p=0.005

72%72%

BMS ControlBMS ControlCYPHERCYPHER®® Stent Stent

4 RCTs: 4 RCTs: Leon M., et al.,Leon M., et al., TCT TCT 2005; Oral Presentation. 2005; Oral Presentation.PRISON 2: Suttorp MJ., et al., PRISON 2: Suttorp MJ., et al., CirculationCirculation 2006;114:921-8. 2006;114:921-8.SES-SMART: Ardissino., SES-SMART: Ardissino., JAMA JAMA 2004; 292:2727-34.2004; 292:2727-34.DIABETES: Sabaté M., et al., DIABETES: Sabaté M., et al., Circulation Circulation 2005;112:2175-83.2005;112:2175-83.DECODE: Chan C., et al., AHA 2005; Oral Presentation.DECODE: Chan C., et al., AHA 2005; Oral Presentation.

SCORPIUS: Baumgart D., et al.,SCORPIUS: Baumgart D., et al., TCT TCT 2006; Oral Presentation.2006; Oral Presentation.TYPHOON: Spaulding C., et al., TYPHOON: Spaulding C., et al., N Engl J MedN Engl J Med 2006;355:1093-104. 2006;355:1093-104.SESAMI: Menichilli, M., et al., PCR 2006; Oral Presentation.SESAMI: Menichilli, M., et al., PCR 2006; Oral Presentation.STRATEGY: Vaglimigli M., et al., STRATEGY: Vaglimigli M., et al., J Am Med AssocJ Am Med Assoc 2005;293:2109-17. 2005;293:2109-17.MISSION: Jukema JW.,MISSION: Jukema JW., AHA AHA 2006, Oral Presentation. 2006, Oral Presentation.

Diabetes*Diabetes*CTO*CTO* Small Small Vessels*Vessels* AMI*AMI*4 RCT 4 RCT

PooledPooled

15

SESSES PESPES OR OR (95% CI)(95% CI)

CORPALCORPAL 22/17722/177 35/18835/188 0.62 0.62 (0.35-1.11)(0.35-1.11)

ISAR-DESIREISAR-DESIRE 13/9113/91 20/9220/92 0.600.60(0.28-1.29)(0.28-1.29)

ISAR-ISAR-DiabetesDiabetes 7/1027/102 17/10317/103 0.370.37

(0.15-0.94)(0.15-0.94)

REALITYREALITY 88/89888/898 95/85595/855 0.850.85(0.62-1.15)(0.62-1.15)

SIRTAXSIRTAX 23/34823/348 44/37544/375 0.530.53(0.31-0.90)(0.31-0.90)

TAXiTAXi -- -- --

OverallOverall 151/1,616151/1,616 211/1,613211/1,613 --

Fixed EffectsFixed Effects 0.680.68(0.55-0.86)(0.55-0.86)

Random Random EffectsEffects

0.670.67(0.52-0.86)(0.52-0.86)

Test for Heterogeneity: p=0.33Test for Heterogeneity: p=0.33Test for Inconsistency: Test for Inconsistency: II2 2 = 13% (95% CI, 0%-57%)= 13% (95% CI, 0%-57%)Test for Overall Effect: p=0.001Test for Overall Effect: p=0.001 Adapted from Kastrati, A., et al., Adapted from Kastrati, A., et al., JAMA JAMA 2005; 294:819-25.2005; 294:819-25.

0.20.2 0.50.5 1.01.0 2.02.0 5.05.0Odds Ratio (95% CI)Odds Ratio (95% CI)

Favors SESFavors SES Favors PESFavors PES

Kastrati, et al., Meta-analysis of CYPHER vs. Taxus RCTsKastrati, et al., Meta-analysis of CYPHER vs. Taxus RCTsSignificantly Lower Angiographic Restenosis with CYPHERSignificantly Lower Angiographic Restenosis with CYPHER

16

Risk RatioRisk Ratio (95% CI)(95% CI) % Weight% Weight

TAXiTAXi 2.94 ( 0.31, 27.80)2.94 ( 0.31, 27.80) 1.0 1.0

ISAR-DESIREISAR-DESIRE 0.42 ( 0.19, 0.92)0.42 ( 0.19, 0.92) 7.3 7.3

ISAR-DIABETESISAR-DIABETES 0.53 ( 0.23, 1.21)0.53 ( 0.23, 1.21) 6.6 6.6

SIRTAXSIRTAX 0.55 ( 0.36, 0.86)0.55 ( 0.36, 0.86) 18.3 18.3

CORPALCORPAL 0.64 ( 0.36, 1.11)0.64 ( 0.36, 1.11) 12.7 12.7

REALITYREALITY 0.96 ( 0.64, 1.44)0.96 ( 0.64, 1.44) 20.0 20.0

BASKETBASKET 0.50 ( 0.22, 1.14)0.50 ( 0.22, 1.14) 6.6 6.6

ISAR-SMART 3ISAR-SMART 3 0.43 ( 0.23, 0.80)0.43 ( 0.23, 0.80) 10.8 10.8

Zhang et alZhang et al 0.73 ( 0.36, 1.45)0.73 ( 0.36, 1.45) 9.0 9.0

Long DES IILong DES II 0.32 ( 0.12, 0.86)0.32 ( 0.12, 0.86) 4.8 4.8

PROSITPROSIT 0.33 ( 0.09, 1.19)0.33 ( 0.09, 1.19) 2.9 2.9

OverallOverall 0.59 ( 0.47, 0.74)0.59 ( 0.47, 0.74),, II22=16.1%=16.1%

0.040.04 0.10.1 0.50.5 11 22 1010 2525

Risk RatioRisk Ratio Favours SESFavours SES Favours PESFavours PES

SIRPACT Meta-analysis of CYPHER vs. Taxus RCTsSIRPACT Meta-analysis of CYPHER vs. Taxus RCTsSignificantly Lower TLR with CYPHERSignificantly Lower TLR with CYPHER

Windecker S., et al., TCT 2005; Poster Presentation.Windecker S., et al., TCT 2005; Poster Presentation.

17

Source: A. Kastrati, FDA Panel Presentation, Washington, DC, December 2006

Kastrati, et al., Meta-analysis of CYPHER vs. Taxus RCTsKastrati, et al., Meta-analysis of CYPHER vs. Taxus RCTsSignificantly Lower MACE with CYPHERSignificantly Lower MACE with CYPHER

N=5,074. Mean follow-up 25.1 months

18

A. Kastrati, FDA Panel Presentation, Washington, DC, December 2006

N=5,074. Mean follow-up 25.1 months

Kastrati, et al., Meta-analysis of Cypher vs. Taxus RCTsKastrati, et al., Meta-analysis of Cypher vs. Taxus RCTsTrend for Lower Death or MI with CypherTrend for Lower Death or MI with Cypher

19

Difference in TLR Rates vs. Average TLR for Difference in TLR Rates vs. Average TLR for the CYPHER Stent vs. Taxus Stentthe CYPHER Stent vs. Taxus Stent

y = 0.9809x - 2.5203

R2 = 0.7788

-4

-2

0

2

4

6

8

10

12

0 5 10 15

* TVR rates

TAXi

SORT OUT II

REALITY

ISAR-DESIRE*

ISAR-SMART 3

ISAR-DIABETES

SIRTAX

CORPALBASKET* (TVR)

PROSIT

Long DES II

The difference between TLR rates for the CYPHER® Stent and Taxus Stent in a given trial correlates with the average TLR for that trial.

The higher the risk, the greater the difference in outcomes..

TLR(%)

TLR (%)

20

OUS OUS e-CYPHERe-CYPHER

US PMSUS PMSe-CYPHER*e-CYPHER*

D.E.S. D.E.S. COVERCOVER S.T.L.L.R.S.T.L.L.R. Japan- PMSJapan- PMS J-CYPHERJ-CYPHER

Study TypeStudy TypeOpen Open

Enrollment Enrollment RegistryRegistry

Open Open Enrollment Enrollment

RegistryRegistry


RegistryRegistry

Angio eval: Angio eval: stent stent

deployment deployment on TVRon TVR


RegistryRegistry


RegistryRegistry

EnrollmentEnrollment 2002-20052002-2005 2003-20042003-2004 2004-20052004-2005 2004-20052004-2005 2004-20052004-2005 2004-20052004-2005

# of # of PatientsPatients 15,15715,157 2,0672,067 4,2354,235 1,5541,554 2,0322,032 14,08714,087

# of Sites# of Sites

LocationLocation

279279

41 Countries41 Countries

3838

United United StatesStates

140140


4141


5050

JapanJapan

4141

JapanJapan

Independent Independent CECCEC YesYes YesYes YesYes YesYes YesYes YesYes

Independent Independent Data MgmtData Mgmt YesYes YesYes YesYes YesYes YesYes YesYes

MonitoringMonitoring 3%3% 100%100% -- -- 100%100% 3%3%

Anti-platelet Anti-platelet MedicationsMedications ASA, Ticlopidine, ClopidogrelASA, Ticlopidine, Clopidogrel ASA, TiclopidineASA, Ticlopidine

Clinical Clinical Follow-upFollow-up 1, 6, and 12 months1, 6, and 12 months Also yearly Also yearly

f/u to 5-yearsf/u to 5-years

Worldwide Experience with CYPHER in Worldwide Experience with CYPHER in Broad, Unselected Patient PopulationsBroad, Unselected Patient Populations

* FDA mandated PMS * FDA mandated PMS

21

1-year F/U in 25,156 Patients - All Events CEC Adjudicated1-year F/U in 25,156 Patients - All Events CEC Adjudicated

0.7

0.2

0.6

0.2

0.40.3

0.20.2 0.3

0.2 0.6

0.3

0.6

0.6

0.2

0.4

0.20.3

0.4

0.30.6

0.4

0

1

2

3

4

e-CYPHER(OUS)

e-CYPHER (US)

J-CYPHER J-PMS DEScover STLLR e-CYPHER(OUS)

e-CYPHER (US)

J-CYPHER J-PMS DEScover STLLR

0.7

0.2

0.6

0.2

0.40.3

0.20.2 0.3

0.2 0.6

0.3

0.6

0.6

0.2

0.4

0.20.3

0.4

0.30.6

0.4

0

1

2

3

4

e-CYPHER(OUS)

e-CYPHER (US)

J-CYPHER J-PMS DEScover STLLR e-CYPHER(OUS)

e-CYPHER (US)


Stent Thrombosis Rates Across 6Stent Thrombosis Rates Across 6RegistriesRegistries

0.90.90.80.8

0.70.7

0.30.30.40.4

0.90.9

Early (0-30 Days)Early (0-30 Days) Late (31-360 Days)Late (31-360 Days)

n=15,157 n=15,157 n=2,067 n=2,067 n=4,235 n=4,235 n=1,554n=1,554 n=8,349 n=8,349 n=2,032n=2,032

(%)

Pat

ien

ts(%

) P

atie

nts

NANA

1.21.20.60.6

EarlyEarly+ Late+ Late 0.50.5

0.60.61.01.0

e-CYPHER(OUS)

e-CYPHER (US PMS)


1 yr F/U1 yr F/U88%88%

1 yr F/U1 yr F/U75%75%

1 yr F/U1 yr F/U89.6%89.6%

1 yr F/U1 yr F/U98%98%

1 yr F/U1 yr F/U93.6%93.6%

1 yr F/U1 yr F/U31%31%

Interim DataInterim Data

Per ProtocolPer Protocol ARC (Def/Prob)ARC (Def/Prob)

23

02468

101214161820

02468

101214161820

DiabeticsDiabeticsAll ComersAll Comers

Long-Term Myocardial Infarction Rates Long-Term Myocardial Infarction Rates (> 1 Year) in CYPHER Stent Studies(> 1 Year) in CYPHER Stent Studies

n= 55 55 684 669 503 509n= 55 55 684 669 503 509 200 392 335 80 80 200 392 335 80 80 272 227 129 128 101 155 206 252 607 600 878 870 653 643 272 227 129 128 101 155 206 252 607 600 878 870 653 643

(%)

Pat

ien

ts(%

) P

atie

nts

All-All-ComersComers

ModModRiskRisk

BMS ControlBMS ControlCYPHERCYPHER®® Stent Stent

On-labelOn-label(n=878)(n=878)

MVDMVDSmall VesselsSmall Vessels ISRISRLMLM

TaxusTaxus

2 years2 years 3 years3 years1.8 y1.8 y 4 y 5 y4 y 5 y

** ** ** **

Valglimigli L, et al. JAMA 2005;293:2109-17.REALITY: Morice MC, ESC 2006; Poster Presentation.SIRTAX: Windecker S, ESC 2006; Poster Presentation.de la Torre, et al., Rev Esp Cardiol 2006; 59:225-31.

ISAR-SMART 3: Mehilla J., et al., AHA 2006; Oral Presentation.DIABETES, et al., ESC 2006; Oral Presentation.Kaiser Perm: TCT 2006; Oral Presentation.SES-SMART: ACC 2005; Oral Presentation.

SVELTE: TCT 2006; Oral Presentation.TROPICAL: TCT 2006; Oral Presentation.RESEARCH: Daemen J., et al., Am J Cardiol 2006; 98:895-901.ARTS II: Serruys PW, et al., TCT 2006; Oral Presentation.4 and 2 RCTs: Internal Data, Cordis Corporation.

NCNC NCNC NCNC

* RCTs* RCTsNC = No ControlNC = No Control

****

2,645 SES Patients Outside of 4 Key Trials with > 1 Year Follow-up2,645 SES Patients Outside of 4 Key Trials with > 1 Year Follow-up

NotNotAvail.Avail.

In addition Registries with longer-term follow-up were presented at the FDA Panel Meeting that can be found on In addition Registries with longer-term follow-up were presented at the FDA Panel Meeting that can be found on www.fda.gov/cdrh/panel/www.fda.gov/cdrh/panel/* The safety and effectiveness of the CYPHER® Stent in these sub-populations have not been established.

24

02468

101214161820

02468

101214161820

Diabetics*Diabetics*All ComersAll Comers

(%)

Pat

ien

ts(%

) P

atie

nts

All-All-ComersComers

ModModRiskRisk On-labelOn-label

(n=878)(n=878)MVD*MVD*Small Vessels*Small Vessels* ISR*ISR*LMLM

2 years2 years 3 years3 years1.8 y1.8 y 4 y 5 y4 y 5 y

2,645 SES Patients Outside of 4 Key Trials with > 1 Year Follow-up2,645 SES Patients Outside of 4 Key Trials with > 1 Year Follow-up

BMS ControlBMS ControlCYPHERCYPHER®® Stent Stent TaxusTaxus * RCTs* RCTsNC = No ControlNC = No Control

n= 55 55 684 669 503 509n= 55 55 684 669 503 509 200 392 335 80 80 200 392 335 80 80 272 227 129128 101 155 206 252 607 600 878 870 653 272 227 129128 101 155 206 252 607 600 878 870 653 643 643

Valglimigli L, et al. JAMA 2005;293:2109-17.REALITY: Morice MC, ESC 2006; Poster Presentation.SIRTAX: Windecker S, ESC 2006; Poster Presentation.de la Torre, et al., Rev Esp Cardiol 2006; 59:225-31.

ISAR-SMART 3: Mehilla J., et al., AHA 2006; Oral Presentation.DIABETES, et al., ESC 2006; Oral Presentation.Kaiser Perm: TCT 2006; Oral Presentation.SES-SMART: ACC 2005; Oral Presentation.

SVELTE: TCT 2006; Oral Presentation.TROPICAL: TCT 2006; Oral Presentation.RESEARCH: Daemen J., et al., Am J Cardiol 2006; 98:895-901.ARTS II: Serruys PW, et al., TCT 2006; Oral Presentation.4 and 2 RCTs: Internal Data, Cordis Corporation.

** ** ** **

Long-Term Mortality Rates Long-Term Mortality Rates (> 1 Year) in CYPHER(> 1 Year) in CYPHER®® Stent Studies Stent Studies

NCNC NCNC NCNC

****

In addition Registries with longer-term follow-up were presented at the FDA Panel Meeting that can be found on In addition Registries with longer-term follow-up were presented at the FDA Panel Meeting that can be found on www.fda.gov/cdrh/panel/www.fda.gov/cdrh/panel/* The safety and effectiveness of the CYPHER® Stent in these sub-populations have not been established.

25

CYPHER Stent: Final ConclusionsCYPHER Stent: Final Conclusions

The CYPHER stent has demonstrated clinically meaningful, The CYPHER stent has demonstrated clinically meaningful, sustained benefit in reducing the need for repeat sustained benefit in reducing the need for repeat revascularizations in a wide array of clinical settings and revascularizations in a wide array of clinical settings and lesion complexitieslesion complexities

– Standard of care, standard for comparison Standard of care, standard for comparison

No difference in overall risk of stent thrombosis in 4 RCTs No difference in overall risk of stent thrombosis in 4 RCTs comparing CYPHER with BMS comparing CYPHER with BMS

– No significant difference in death, and death or MINo significant difference in death, and death or MI

– Temporal distribution of stent thrombosis may vary Temporal distribution of stent thrombosis may vary between CYPHER Stent and BMSbetween CYPHER Stent and BMS

Systematic overview of CYPHER vs. Taxus RCTs demonstrate Systematic overview of CYPHER vs. Taxus RCTs demonstrate significantly lower TLR and MACE in favor of the CYPHER significantly lower TLR and MACE in favor of the CYPHER StentStent

– Trend for lower death/MI Trend for lower death/MI (OR 95% CI: 0.86 [0.72, 1.02])(OR 95% CI: 0.86 [0.72, 1.02])

26

In high-risk patient subgroups, different risk: benefit In high-risk patient subgroups, different risk: benefit ratio compared to 4 key CYPHER trials:ratio compared to 4 key CYPHER trials:

Benefit similar to lower risk groups:Benefit similar to lower risk groups:– Significant relative reductions in TLR/TVR of the Significant relative reductions in TLR/TVR of the

CYPHER Stent:CYPHER Stent:• 62-80% vs. BMS62-80% vs. BMS• 41-45% vs. PES 41-45% vs. PES

Risk: Risk: – Rates of death, MI, or stent thrombosis Rates of death, MI, or stent thrombosis

numerically higher than on-label trials:numerically higher than on-label trials:• No significant differences between the CYPHER Stent No significant differences between the CYPHER Stent

and BMSand BMS• Elevated risk related to patient and lesion subgroupsElevated risk related to patient and lesion subgroups• Some data suggest differential risk profile of SES vs. Some data suggest differential risk profile of SES vs.

PESPES

CYPHER Stent: Final ConclusionsCYPHER Stent: Final Conclusions

27

Commitments to Interventional CommunityCommitments to Interventional Community

Extend follow-up of 3 SIRIUS Trials to 8 yearsExtend follow-up of 3 SIRIUS Trials to 8 years

Coordinate the extended follow-up of 10 RCTs Coordinate the extended follow-up of 10 RCTs (n=4,500 patients) to 5 years(n=4,500 patients) to 5 years

Collaborate with regulatory agencies and Collaborate with regulatory agencies and professional societies to develop approval pathways professional societies to develop approval pathways for expanded indicationsfor expanded indications

Enable Interventional Cardiologists to improve Enable Interventional Cardiologists to improve patient outcomes through new device design and patient outcomes through new device design and clinical trialsclinical trials

28

Back-Up SlidesBack-Up Slides

29

1-year RCTs1-year RCTs

DECODEDECODE SCORPIUSSCORPIUS

P=NSP=NS P=NSP=NS

0.0

6.95.3

4.26.3

5.0

9.111.0 11.8

4.3

9.6

0

10

20

30

0.0

6.95.3

4.26.3

5.0

9.111.0 11.8

4.3

9.6

0

10

20

304-year 4-year post-hocpost-hoc

subgroup analysessubgroup analyses

DIABETESDIABETES

P=NSP=NS

2-year RCT2-year RCT

Summary of Contemporary Diabetic Summary of Contemporary Diabetic Mortality DataMortality Data

n = n = 54 54 29 29 95 95 95 95 80 80 80 80 399 399 415 415 195 195 233 233 263263

*Lee T et al., Am J Cardiol, 2006; 98:718-721*Lee T et al., Am J Cardiol, 2006; 98:718-721DIABETES: Sabaté M., et al., DIABETES: Sabaté M., et al., ESCESC 2006; Oral Presentation. 2006; Oral Presentation. DECODE: Chan C., et al., AHA 2005; Oral Presentation.DECODE: Chan C., et al., AHA 2005; Oral Presentation.SCORPIUS: Baumgart D., et al.,SCORPIUS: Baumgart D., et al., TCT TCT 2006; Oral Presentation. 4 key RCTs CYPHER® Stent: Internal Data, Cordis Corporation.2006; Oral Presentation. 4 key RCTs CYPHER® Stent: Internal Data, Cordis Corporation.Letter from Don Baim, M.D.Letter from Don Baim, M.D.

BMSBMSSESSES PESPES

% P

atie

nts

% P

atie

nts P=NSP=NS

4 Key RCTs4 Key RCTsTaxus StentTaxus Stent

P=0.006P=0.006

4 Key RCTs4 Key RCTsCYPHER® StentCYPHER® Stent

5-year 5-year Follow-up Follow-up of BMS Published of BMS Published

DataData**

30

Low Mortality in BMS arm of CYPHER Low Mortality in BMS arm of CYPHER TrialsTrials

Four-Year Follow-up of Sirolimus-eluting Stents in Comparison with Bare Metal Stents: A Pooled Safety Analysis of the RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS Trials in 1,748 Patients, Patrick Serruys, Erasmus Medical Center: Downloaded

01/05/2007: http://www.fda.gov/ohrms/dockets/ac/06/slides/2006-4253oph1_index.htm

1 contemporary pci with the cypher ® stent: the standard of care and comparison david e. kandzari,...

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