2007, The Year in PCI Asad Pathan FACC FSCAI March 15 th, 2008.

2007, The Year in PCI2007, The Year in PCI

Asad Pathan Asad Pathan

FACC FSCAIFACC FSCAI

March 15th, 2008

2007, The Year in PCI2007, The Year in PCI DESDES

– RegistriesRegistries– New stentsNew stents

AnticaogulantsAnticaogulants– BivalirudinBivalirudin

Stable CADStable CAD– COURAGE trialCOURAGE trial

AMIAMI– Technique/aspirationTechnique/aspiration

New DevicesNew Devices– Drug Eluting balloonDrug Eluting balloon

Drug Eluting StentsDrug Eluting Stents

DES vs BMSDES vs BMSRecent Registry Data Recent Registry Data

0.6

5.34.5

6.4

0.8

7.9

3.7

7.9

0

2

4

6

8

10

12

14

Death MI TLR Total ST

% o

f ev

ent

Western Denmark Clinical endpoints to 2 years (unadjusted)

NS

P=0.004

NS

P<0.0001

DES ( N=8847)

BMS (N=3548)

Jensen TCT 2007

0.2

5.3

2.02.4

0.04

7.90

1.002.20

0

2

4

6

8

10

12

14

Death MI TLR* Definite ST

% o

f ev

ent

DES ( N=8847)

BMS (N=3548)

Western Denmark Clinical endpoints >1 to 2 years

P=0.02

P<0.0001

P=0.0019

P<0.001

*2 yr cumulativeAdjusted P values

Jensen TCT 2007

9.3

7.4

5.24.3

10.510.7

5.76.1

0

2

4

6

8

10

12

14

Death MI TVR Death/MI

% o

f ev

ent

Ontario Registry Clinical endpoints to 2 years in propensity matched

cohort

P=0.001 P=0.95

P<0.001

DES ( N=3751)

BMS (N=3751)

P=0.02

Tu et al. N Engl J Med 2007;357:1393-1402.

3.2

2.21.9

1.6

3.0

2.1

1.3

2.1

0

2

4

Death MI TVR Death/MI

% o

f ev

ent

Ontario Registry Clinical endpoints > 1 to 2 years in propensity

matched cohortDES ( N=3751)

BMS (N=3751)

P values not available

Tu et al N Engl J Med 2007;357:1393-1402.

Mauri AHA 2007

Stefan James, Jörg Carlsson, Johan Stefan James, Jörg Carlsson, Johan Lindbäck, Tage Nilsson, Ulf Stenestrand, Lindbäck, Tage Nilsson, Ulf Stenestrand, Lars Wallentin and Bo Lagerqvist for the Lars Wallentin and Bo Lagerqvist for the

SCAAR study groupSCAAR study groupNone of the authors have any conflicts of interest in relation to the

presentation

Long term outcome with drug eluting stents vs

bare metal stents in Sweden – one additional year of follow-up

RestenosisRestenosisone stent cohortone stent cohort

0 1 2 3 40

.00

0.0

20

.04

0.0

60

.08

0.1

0

2004-2005, Adjusted

Time (years)

Cu

mu

lativ

e r

isk

of r

est

en

osi

s

BMSDES

BMS 8235 7708 7505 6326 4602 2668 753 0 0DES 5438 5223 5097 3809 2294 1110 257 0 0

RR: 0.48 (0.39, 0.58)

0 1 2 3 4

0.0

00

.02

0.0

40

.06

0.0

80

.10

2004-2005, Crude

Time (years)

Cu

mu

lativ

e r

isk

of r

est

en

osi

s

BMSDES

BMS 9217 8615 8399 7147 5205 3057 887 0 0DES 6229 5967 5822 4429 2738 1334 317 0 0

Unadjusted Adjusted

James ESC 2007

0 1 2 3 4

0.0

00

.05

0.1

00

.15

0.2

00

.25

2003-2005, Adjusted

Time (years)

Cu

mu

lativ

e r

isk

of d

ea

th o

r M

I

BMSDES

BMS 18769 17326 16957 14414 11596 8755 5523 2934 7DES 12015 11286 11003 7648 4956 3062 1498 535 0

RR: 1.01 (0.94, 1.09)

Adjusted death /MIAdjusted death /MI

0 1 2 3 4

0.0

00

.05

0.1

00

.15

0.2

00

.25

2003-2005, Adjusted

Time (years)

Cu

mu

lativ

e r

isk

of d

ea

th o

r M

I

BMSDES

BMS 12556 11701 11453 9731 7799 5878 3739 1977 7DES 6381 6017 5875 4103 2644 1631 798 295 0

RR: 0.91 (0.82, 1.01)

Total cohort

N = 35 262

One stent cohort

N = 18 937

James ESC 2007

Death/MI-total cohort

Year by year

0 1 2 3 4

0.0

00

.05

0.1

00

.15

0.2

00

.25

2003 landmark

Time (years)

Cu

mu

lativ

e r

isk

of d

ea

th o

r M

I

BMSDES

BMS 6448 6037 5918 5820 5713 5612 5520 2934 7DES 1799 1685 1644 1607 1568 1539 1496 535 0

RR: 1.06 (0.86, 1.32)

RR: 1.31 (1.12, 1.53)

2003

0 1 2 3 4

0.0

00

.05

0.1

00

.15

0.2

00

.25

2004 landmark

Time (years)

Cu

mu

lativ

e r

isk

of d

ea

th o

r M

I

BMSDES

BMS 6737 6228 6090 5983 5883 3143 3 0 0DES 3880 3638 3550 3468 3388 1523 2 0 0

RR: 0.98 (0.83, 1.17)

RR: 1.22 (1.05, 1.43)

2004

0 1 2 3 4

0.0

00

.05

0.1

00

.15

0.2

00

.25

2005 landmark

Time (years)

Cu

mu

lativ

e r

isk

of d

ea

th o

r M

I

BMSDES

BMS 5584 5061 4949 2611 0 0 0 0 0DES 6336 5963 5809 2573 0 0 0 0 0

RR: 0.69 (0.59, 0.81)

RR: 0.93 (0.76, 1.13)

2005

James ESC 2007

Stent thrombosisStent thrombosis

Time (years)210

Cu

mu

lati

ve r

isk

of

sten

t th

rom

bo

sis

% 2

1

0

DES n=21 717BMS n=20 058

Stent type Total cohort

N = 41 775 stents

0.5% per year

Unadjusted

James ESC 2007

P < 0.001

All

cau

se m

ort

alit

y ra

te (

%) P = 0.052

P = NR

P < 0.001

P < 0.0001

P < 0.001 P = 0.004

N =

31

60

N =

40

61

N =

48

3

N =

87

1

N =

57

19

N =

53

99

N =

63

84

N =

78

34

N =

37

51

N =

37

51

N =

59

96

N =

13

59

N =

35

48

N =

88

47

BMS

DES

3-year 3-year 2-year 2-year 3-year 2-year 2-year

DES vs BMS registries at TCT 07DES vs BMS registries at TCT 07

SJ Park Harjai Vagonescu Hannan Ko B Brodie Jensen

DES vs. BMSDES vs. BMSConclusionsConclusions

Over 35,000 patients with DES, 2-4 year follow-Over 35,000 patients with DES, 2-4 year follow-up with adjustment for differences in back up with adjustment for differences in back ground characteristics:ground characteristics:

– No overall increase in mortality or risk of MI with DES No overall increase in mortality or risk of MI with DES use.use.

Reduced mortality in some of the registriesReduced mortality in some of the registries

– Sustained reduction in risk of TVR.Sustained reduction in risk of TVR.

– Slightly increased risk of ST and MI after initial 6 Slightly increased risk of ST and MI after initial 6 months, compensated by reduction of events in the months, compensated by reduction of events in the first 6 months.first 6 months.

New DES ResultsNew DES ResultsEverolimus-Eluting Everolimus-Eluting

XIENCE™ V chromium XIENCE™ V chromium cobalt stent. cobalt stent.

The SPIRIT of XIENCE™The SPIRIT of XIENCE™The SPIRIT Family of TrialsThe SPIRIT Family of Trials

Post-Post-CE Mark CE Mark ApprovalApproval

InternationalInternationalN = 2,000N = 2,000

Women onlyWomen only

SPIRIT SPIRIT WOMENWOMEN

Post-Post-CE Mark CE Mark ApprovalApproval

InternationalInternationalN = 3,000N = 3,000

Diabetic study Diabetic study N = 300 N = 300 RegistryRegistryN = 2,700N = 2,700

SPIRIT SPIRIT VV

US Peri US Peri ApprovalApproval

USUSN = 3,690N = 3,690

SPIRIT SPIRIT IVIV

Safety & Safety & PerformancePerformance

EuropeEuropeN = 60N = 60

SPIRIT SPIRIT FIRSTFIRST

Clinical Clinical Support for Support for CE LaunchCE Launch

InternationalInternationalN = 300N = 300

SPIRIT SPIRIT IIII

US & Japan US & Japan ApprovalApproval

US/ JapanUS/ JapanN = 1,380N = 1,380

(1,292/88)(1,292/88)

SPIRIT SPIRIT IIIIII

22::11

Up to two de Up to two de novo lesions, novo lesions,

maximum of one maximum of one lesion per lesion per

epicardial vesselepicardial vessel

Main US RCTMain US RCT2.5 – 3.75 mm*2.5 – 3.75 mm*

LL ≤ 28 mmLL ≤ 28 mmN N = 1,002= 1,002

XIENCE™ VXIENCE™ VN = 669N = 669

TAXUS® Control TAXUS® Control N = 333N = 333

• PI: Gregg Stone, MDPI: Gregg Stone, MD• RCT: Prospective, single blindRCT: Prospective, single blind• Primary end point: In-segment Late Loss at 8MPrimary end point: In-segment Late Loss at 8M• Stent Size: 2.5 – 3.5mm mm; Stent lengths: 8, 18, 28 mmStent Size: 2.5 – 3.5mm mm; Stent lengths: 8, 18, 28 mm• Angiographic and IVUS Follow-Up on 564 and 240 pts, respectively Angiographic and IVUS Follow-Up on 564 and 240 pts, respectively • Clinical follow-up at 30, 180, 270d and 1, 2, 3, 4 and 5 yearsClinical follow-up at 30, 180, 270d and 1, 2, 3, 4 and 5 years• 6 Months clopidogrel for all arms6 Months clopidogrel for all arms

SPIRIT IIISPIRIT III

SPIRIT III RCT DesignSPIRIT III RCT Design

Baseline DemographicsBaseline Demographics

XIENCE™ VXIENCE™ V 669 pts669 pts

TAXUSTAXUS®® 333 pts333 pts P-valueP-value

Age (in years)Age (in years) 63.2 63.2 ± ± 10.510.5 62.8 62.8 ± ± 10.210.2 0.540.54

Male (%)Male (%) 70.170.1 65.765.7 0.170.17

Hypertension Hypertension (%)(%) 76.276.2 74.074.0 0.480.48

Hypercholesterolemia Hypercholesterolemia (%)(%) 74.274.2 71.571.5 0.360.36

Diabetes mellitus (%)Diabetes mellitus (%) 29.629.6 27.927.9 0.600.60

Insulin requiring (%)Insulin requiring (%) 7.87.8 5.55.5 0.190.19

Current smoker Current smoker (%)(%) 23.423.4 22.522.5 0.810.81

Prior MI (%)Prior MI (%) 19.919.9 18.018.0 0.490.49

Unstable angina (%)Unstable angina (%) 18.718.7 25.125.1 0.020.02

SOURCE: G.W. Stone, ACC 2007.SOURCE: G.W. Stone, ACC 2007.

Baseline AngiographyBaseline AngiographyXIENCE™ VXIENCE™ V 767 lesions 767 lesions

TAXUSTAXUS®® 382 lesions382 lesions P-valueP-value

Lesion location Lesion location

LADLAD 41.3%41.3% 42.9%42.9% 0.610.61

LCXLCX 27.6%27.6% 28.3%28.3% 0.830.83

RCARCA 31.0%31.0% 28.5%28.5% 0.410.41

LMCALMCA 0.1%0.1% 0.3%0.3% 0.550.55

QCAQCA

RVD (mm)RVD (mm) 2.77 ± 0.452.77 ± 0.45 2.76 ± 0.462.76 ± 0.46 0.870.87

MLD (mm)MLD (mm) 0.82 ± 0.410.82 ± 0.41 0.83 ± 0.400.83 ± 0.40 0.790.79

% DS% DS 70.0 ± 13.370.0 ± 13.3 69.4 ± 13.669.4 ± 13.6 0.540.54

Lesion length (mm)Lesion length (mm) 14.7 ± 5.614.7 ± 5.6 14.7 ± 5.714.7 ± 5.7 0.920.92

SOURCE: G.W. Stone, ACC 2007.SOURCE: G.W. Stone, ACC 2007.

QCA at 8 Months (All Lesions)QCA at 8 Months (All Lesions)XIENCE™ VXIENCE™ V 344 lesions 344 lesions

TAXUSTAXUS®® 158 lesions158 lesions P-valueP-value

RVD (mm)RVD (mm) 2.77 ± 0.432.77 ± 0.43 2.78 ± 0.422.78 ± 0.42 0.840.84

MLD (mm)MLD (mm)

In-segmentIn-segment 2.22 ± 0.532.22 ± 0.53 2.12 ± 0.602.12 ± 0.60 0.080.08

In-stentIn-stent 2.56 ± 0.532.56 ± 0.53 2.45 ± 0.652.45 ± 0.65 0.070.07

Late Loss (mm)Late Loss (mm)


In-stentIn-stent 0.16 ± 0.410.16 ± 0.41 0.30 ± 0.530.30 ± 0.53 0.0020.002

Diameter Stenosis (%)Diameter Stenosis (%)


In-stentIn-stent 5.9 ± 16.45.9 ± 16.4 10.3 ± 21.410.3 ± 21.4 0.020.02

Binary Restenosis (%)Binary Restenosis (%)

In-segmentIn-segment 4.74.7 8.98.9 0.070.07

In-stentIn-stent 2.32.3 5.75.7 0.060.06SOURCE: G.W. Stone, ACC 2007.

SPIRIT III Clinical Results SPIRIT III Clinical Results

0.5% 0.5%

2.0%2.6%

4.6%

0.0%0.6%

2.5%

5.0%

8.1%

0%

2%

4%

6%

8%

10%

StentThrombosis

CardiacDeath

MI TLR MACE

XIENCE V TAXUS®N = 658N = 658 N = 322N = 322

P = 0.55P = 0.55 P = 0.67P = 0.67 P = 0.64P = 0.64 P = 0.053P = 0.05344% Reduction44% Reduction

P = 0.028P = 0.028

G.W. Stone, ACC 2007.G.W. Stone, ACC 2007.

Meta-Analysis of Meta-Analysis of Patient Level Data Patient Level Data N = 1,302N = 1,302

SPIRIT II & III Pooled Meta-SPIRIT II & III Pooled Meta-AnalysisAnalysis

Similar inclusion and Similar inclusion and exclusion criteria: Up exclusion criteria: Up

to two de novo to two de novo lesions, maximum of lesions, maximum of

one lesion per one lesion per epicardial vessel epicardial vessel

2.5 – 3.75 mm*2.5 – 3.75 mm*LL ≤ 28 mmLL ≤ 28 mm

XIENCE™ VXIENCE™ VN = 892N = 892

TAXUS® Control TAXUS® Control N = 410N = 410

SPIRIT II + IIISPIRIT II + III

• Presented by Gregg Stone, MD at PCR, 5/22/07Presented by Gregg Stone, MD at PCR, 5/22/07• Independent Meta-Analysis done by CRFIndependent Meta-Analysis done by CRF• SPIRIT II and SPIRIT III have similar inclusion and SPIRIT II and SPIRIT III have similar inclusion and

exclusion criteriaexclusion criteria• Pooled, patient level analysis of combined SPIRIT II and Pooled, patient level analysis of combined SPIRIT II and

SPIRIT III dataSPIRIT III data• Pre-specified, Superiority Testing on all endpointsPre-specified, Superiority Testing on all endpoints

*SPIRIT II was up to 4.0mm

SPIRIT II & III Meta-AnalysisSPIRIT II & III Meta-Analysis

0.14

0.11

0.33

0.22

0.00

0.10

0.20

0.30

0.40

In-stent In-segment

XIENCE V TAXUS®

Late LossLate Loss Binary RestenosisBinary Restenosis

mm

mm

1.9%

4.1%

4.9%

7.8%

0%

2%

4%

6%

8%

10%

In-stent In-segment

58% Reduction58% ReductionP < 0.0001P < 0.0001

50% Reduction50% ReductionP = 0.0004P = 0.0004



N = 581N = 581 N = 244N = 244SOURCE: G.W. Stone, PCR 2007.SOURCE: G.W. Stone, PCR 2007.NOTE: This analysis was performed by the SPIRIT III investigator and is meant for descriptive purposes only. Please note that the data were NOTE: This analysis was performed by the SPIRIT III investigator and is meant for descriptive purposes only. Please note that the data were from different patient populations (OUS vs. US) and had different angiographic follow-up time points (6 months vs. 8 months). from different patient populations (OUS vs. US) and had different angiographic follow-up time points (6 months vs. 8 months).

SPIRIT II & III Meta-AnalysisSPIRIT II & III Meta-Analysis

0.5%

1.7%

0.4%

2.1%

0.9%

2.4%

0.3%

2.7%

0.8%

3.2%

1.0%

3.5%

0%

1%

2%

3%

4%

5%

StentThrombosis

MI CardiacDeath

CardiacDeath or MI

All Death All Death orMI

XIENCE V TAXUS®N = 878N = 878 N = 398N = 398

9M E

ven

t R

ate

9M E

ven

t R

ate

P = 0.59P = 0.59 P = 0.22P = 0.22 P = 0.32P = 0.32 P = 0.19P = 0.19 P = 0.87P = 0.87 P = 0.31P = 0.31

Safety EndpointsSafety Endpoints

SOURCE: G.W. Stone, PCR 2007.SOURCE: G.W. Stone, PCR 2007.

Number at riskNumber at riskXIENCE™ VXIENCE™ V 892892 879879 867867 793793TAXUSTAXUS 408408 397397 389389 349349

Isch

emic

TL

R (

%)

Isch

emic

TL

R (

%)

Time in months

HR [95% CI]0.47 [0.26,0.87]

p=0.01

XIENCE VXIENCE V TAXUSTAXUS

5.1%

2.4%

9630

8

10

6

4

2

0

SPIRIT II & III TLRSPIRIT II & III TLR


Number at riskNumber at riskXIENCE™ VXIENCE™ V 888888 871871 858858 783783TAXUSTAXUS 407407 388388 380380 341341

Isch

emic

MA

CE

(%

)Is

chem

ic M

AC

E (

%)

Time in monthsTime in months

HR [95% CI]0.50 [0.31,0.81]

p=0.004

XIENCE VXIENCE V TAXUSTAXUS

8.0%

4.1%

9630

8

10

6

4

2

0

SPIRIT II & III MACESPIRIT II & III MACE


SPIRIT III Conclusions ISPIRIT III Conclusions I In the large, multicenter, randomized SPIRIT III trial, In the large, multicenter, randomized SPIRIT III trial,

the Everolimus-Eluting XIENCE™ V stent compared to the Everolimus-Eluting XIENCE™ V stent compared to

the Paclitaxel-Eluting TAXUSthe Paclitaxel-Eluting TAXUS® ® stent:stent:

– Was both non-inferior and superior in reducing in-Was both non-inferior and superior in reducing in-

segment late loss, the primary endpoint of the trialsegment late loss, the primary endpoint of the trial

– Significantly reduced in-stent late loss at 8 monthsSignificantly reduced in-stent late loss at 8 months

– Reduced angiographic FU diameter stenosis with a Reduced angiographic FU diameter stenosis with a

strong trend toward lower binary restenosisstrong trend toward lower binary restenosis

– Resulted in a significant reduction in in-stent volume Resulted in a significant reduction in in-stent volume

obstruction without excess late acquired malappositionobstruction without excess late acquired malapposition

SPIRIT III Conclusions IISPIRIT III Conclusions II In the large, multicenter, randomized SPIRIT III trial, the In the large, multicenter, randomized SPIRIT III trial, the

Everolimus-Eluting XIENCE™ V stent compared to the Everolimus-Eluting XIENCE™ V stent compared to the

Paclitaxel-Eluting TAXUSPaclitaxel-Eluting TAXUS®® stent: stent:

Demonstrated non-inferior rates of TVF at 9-months, with a Demonstrated non-inferior rates of TVF at 9-months, with a

significant 44% reduction in MACEsignificant 44% reduction in MACE

Showed a strong trend toward reduced ischemia-driven TLR, with a Showed a strong trend toward reduced ischemia-driven TLR, with a

significant reduction in any TLRsignificant reduction in any TLR

Had similar rates of death, MI and stent thrombosisHad similar rates of death, MI and stent thrombosis

The primary and major secondary endpoints of the SPIRIT III The primary and major secondary endpoints of the SPIRIT III

trial were mettrial were met

BivalirudinBivalirudin

Rationale for Use: Pharmacologic Intervention in Rationale for Use: Pharmacologic Intervention in ThrombosisThrombosis

UFH=unfractionated heparin.LMWH=low-molecular-weight heparinADP=adenosine diphosphate.TFPI=tissue factor pathway inhibitor

Selwyn A. Am J Cardiol. 2003;91:3H-11H.

Coagulation cascade Platelets

LMWH

Thienopyridines

GP IIb/IIIa inhibitors

Thrombolytics

LMWHUFH

LMWHUFH

Direct thrombininhibitors

Tissue factor

Factor Xa

Prothrombin

Thrombin

Platelets

A2 vWF ADP

Activated platelets

Fibrinogen cross-linking

Platelet aggregation

Aspirin

Fibrinogen Fibrin Fibrindegradation

Collagen Leukocytes

TFPI

Anti-thrombin

Anti-thrombin

Thromboxane

PlasminThrombus

Conclusion HORIZONS AMIConclusion HORIZONS AMI

Bivalirudin used during acute STEMI PCI Bivalirudin used during acute STEMI PCI as mono-therapy when compared to as mono-therapy when compared to heparin + IIb/IIIa, heparin + IIb/IIIa, Reduced bleeding complication.Reduced bleeding complication.Similar MACESimilar MACEReduce cardiac death. Reduce cardiac death.

COURAGE: COURAGE: CClinicallinical OOutcomesutcomes UUtilizingtilizing RRevascularizationevascularization and and AAggressive ggressive

GGuideline-Drivenuideline-Driven Drug Drug EEvaluationvaluation

Boden W et al. NEJM. 2007;356:1503-1516.

CharacteristicPCI + OMT (N=1149)

OMT (N=1138) P Value

Age – yr. 62 ± 10.1 62 ± 9.7 0.54

Sex % 0.95

Male 85 % 85 %

Female 15 % 15 %

Race or Ethnic group % 0.64

White 86 % 86 %

Non-white 14 % 14 %

CLINICAL

Angina (CCS – class) % 0.24

0 and I 42 % 43 %

II and III 59 % 56 %

Median angina duration 5 (1-15) months 5 (1-15) months

Median angina episodes/week 3 (1-6) 3 (1-6)

Baseline Clinical andBaseline Clinical andAngiographic CharacteristicsAngiographic Characteristics

42 % 43 %

3 (1-6) 3 (1-6)

Boden W et al. NEJM. 2007;356:1503-1516.

CharacteristicPCI + OMT (N=1149)

OMT (N=1138) P Value

CLINICAL

Stress test 0.84 Total patients – % 85 % 86 % Treadmill test 57 % 57 % 0.84 Pharmacologic stress 43 % 43 %Nuclear imaging – % 70 % 72 % 0.59 Single reversible defect 22 % 23 % 0.09 Multiple reversible defects 65 % 68 % 0.09ANGIOGRAPHIC Vessels with disease – % 0.72 1, 2, 3 31, 39, 30 % 30, 39, 31 % Disease in graft 62 % 69 % 0.36 Proximal LAD disease 31 % 37 % 0.01 Ejection fraction 60.8 ± 11.2 60.9 ± 10.3 0.86

Baseline Clinical andBaseline Clinical andAngiographic CharacteristicsAngiographic Characteristics

70% Multi-vessel Disease




Boden W et al. NEJM. 2007;356:1503-1516.

PCI OutcomesPCI Outcomes1149 patients total1149 patients total

46 (4%) procedure not attempted46 (4%) procedure not attempted27 (2%) no lesions crossed27 (2%) no lesions crossed

1077 patients (94%) had PCI attempted1077 patients (94%) had PCI attempted

1577/1688 lesions had PCI success (93%)1577/1688 lesions had PCI success (93%)

787 patients (69%) had 2 or 3 vessel ds.787 patients (69%) had 2 or 3 vessel ds.590 pts (59%) received 1 stent590 pts (59%) received 1 stent

416 pts (41%) received ≥2 stents416 pts (41%) received ≥2 stentsAt least 371 of 787 pts (47%) with multivessel At least 371 of 787 pts (47%) with multivessel

disease had incomplete revascularization disease had incomplete revascularization

Boden WE et al. Boden WE et al. NEJMNEJM. 2007;356:1503-1516.. 2007;356:1503-1516.

97% BMS97% BMS3% DES3% DES

COURAGE COURAGE "Hard Outcomes""Hard Outcomes"

7.69.3

21.6

31.6

10.48.3

0

5

10

15

20

25

30

35

% o

f P

atie

nts

PCIPCI OMTOMT PCIPCI OMTOMT PCIPCI OMTOMT

DeathDeath Spontaneous MISpontaneous MI RevascularizationRevascularization

9%11%

33%

with DES

Moses, J. Data Analysis. April 2007

COURAGE Nuclear Sub-study II

Leslee J. Shaw, Daniel S. Berman, David J. Maron, G. B. John Mancini, Sean W. Hayes, Pamela M. Hartigan, William S. Weintraub, Robert A. O’Rourke, Marcin

Dada, John A. Spertus, Bernard R. Chaitman, John Friedman, Piotr Slomka, Gary V. Heller, Guido Germano, Gilbert Gosselin, Peter Berger, William J. Kostuk,

Ronald Schwartz, Merill Knudtson, Emir Veledar, Eric R. Bates, Benjamin McCallister, Koon K. Teo, William E. Boden for the COURAGE Investigators

Nuclear substudy (n=314 /

2287)

Shaw et al. J Nucl Cardiol 2006;13:685-98.

Documented pre-Rx ischemia

PCI + OMT(n=159)

OMT (n=155)

Repeat MPS*at 6-18m

Repeat MPS*at 6-18m

Hypothesis: reduction in ischemia will be greater for patients randomized to PCI+OMT than for those randomized to OMT

Serial rest/stress myocardial perfusion SPECT (MPS)

*timing chosen to occur beyond window of in-stent restenosis & delayed to allow effects of medical Rx to be observed

• pre-Rx = off meds

to compare patient management strategy for ischemia reduction

• 6-18m = on meds

Mean = 374 ±50 days

% ischemic myocardium:% ischemic myocardium: (stress TPD-rest TPD)(stress TPD-rest TPD) < 5%: minimal (“no ischemia”)< 5%: minimal (“no ischemia”) 5.0%-9.9%: mild5.0%-9.9%: mild 10%: moderate-to-severe10%: moderate-to-severe

Significant reduction in ischemia:Significant reduction in ischemia: 5% reduction in ischemic myocardium*5% reduction in ischemic myocardium*

MPS ischemia based onMPS ischemia based ontotal perfusion deficit (TPD)total perfusion deficit (TPD)

Slomka et al. J Nucl Cardiol 2005;12:66-77

Defect extent

TPD Lower NllimitLower Nllimit

DefectseverityDefectseverity

TPD: quantitative measure of defect extent & severity

*threshold exceeds test repeatability*threshold exceeds test repeatability

OMT (n=155)PCI + OMT (n=159)PCI + OMT (n=159)

Mean = -2.7% (95% CI = -3.8% to -1.7%)

8.6% 8.1%

(6.9%-9.4%)

8.2% 5.5%

(4.7%-6.3%)

MPS % ischemic myocardium (95% CI) pre-Rx & 6-18m

Mean = -0.5% (95% CI = -1.6% to 0.6%)

p<0.0001

Primary endpoint: % with ischemia Primary endpoint: % with ischemia reduction ≥ 5% myocardium reduction ≥ 5% myocardium

(N=314)(N=314)

19.8% p=0.004

33.3%

Isch

emia

redu

ctio

n ≥

5%

52.0% p=0.007

78.0%

Isch

emia

redu

ctio

n ≥

5%

% with ischemia reduction ≥5% myocardium

(n=105 moderate-to-severe pre-Rx ischemia)

RR=0.47 (95% CI=0.23-0.95)

p=0.037

Rates of death or MI by ischemia reductionRates of death or MI by ischemia reductionD

eath

or M

I rat

e (%

)

24.7%

13.4%

(n=82) (n=232)

pp=0.001=0.001

Rates of death or MI by ischemia reduction in subset of 105 patients with

moderate-to-severe pre-Rx ischemia

(n=68) (n=37)

32.4%

16.2%

Dea

th o

r MI r

ate

(%)

Rates of death or MI by residual Rates of death or MI by residual ischemia on 6-18m MPSischemia on 6-18m MPS

p=0.063

p=0.023

p=0.002

(n=23) (n=88)(n=141) (n=62)

22.3%

0.0%

39.3%

15.6%

Dea

th o

r MI r

ate

(%)

Conclusions Conclusions

PCI added to OMT was more effective in reducing ischemia and improving angina than OMT, particularly in patients with moderate-to-severe pre-Rx ischemia

Randomized trials of management strategies should evaluate quantitative measures of myocardial perfusion ischemia to guide clinical decisions regarding revascularization during long-term management

Drug Eluting BalloonDrug Eluting Balloon

Scheller Heart 2007, 93: 539-41

DES vs. DEB (PACCOCATH)DES vs. DEB (PACCOCATH)

Hwang, Circulation 2001; 104: 600-5

Instant and short term drug release from balloon

~ 300 - 600 µg PaclitaxelNo polymeresNo permanent mechanical irritation

Stenting optional

Slow and continuous drug release from stent struts

~100 - 200 µg Paclitaxel / Sirolimus

Polymeres with associated reactions

Implies stent deployment

DES

DEB

The The PPaclitaxel-aclitaxel-EEluting luting PPTCA-Balloon TCA-Balloon Catheter in Catheter in CCoronary oronary AArtery rtery DDiseaseisease

PEPCAD I-SVDPEPCAD I-SVD

PEPCAD II-ISRPEPCAD II-ISR

Outcome ComparisonDEB ITTDEB ITT

N=120N=120

DEB OnlyDEB Only

N=82N=82

Taxus*Taxus* BMS*BMS*

Follow-up Follow-up [mo][mo]

6.4±1.36.4±1.3 6.4±1.26.4±1.2 99 99

Late loss Late loss [mm][mm]

0.32±0.560.32±0.56 0.18±0.380.18±0.38 0.490.490.610.61 0.900.900.630.63

Restenosis Restenosis (segment)(segment)

15.5%15.5% 5.5%5.5% 31.2%31.2% 49.4%49.4%

Total MACETotal MACE 15%15% 6.1%6.1% 18.9%18.9% 26.9%26.9%

TLRTLR 11.7%11.7% 4.9%4.9% 10.4%10.4% 21.5%21.5%

Myocardial Myocardial infarctioninfarction

1.7%1.7% 1.2%1.2% 5.7%5.7% 2.2%2.2%

Cardiac deathCardiac death 0%0% 0%0% 1.9%1.9% 1.1%1.1%

*Stone, G JAMA 2005;294:1215-23

Summary PEPCAD I Summary PEPCAD I

The paclitaxel-eluting balloon catheter The paclitaxel-eluting balloon catheter Sequent PleaseSequent Please (B.Braun Melsungen AG) (B.Braun Melsungen AG) … … –was safe and associated with a high was safe and associated with a high procedural success rate in de-novo lesions procedural success rate in de-novo lesions

–exhibited low late lumen loss after 6 months in exhibited low late lumen loss after 6 months in SVDSVD

–patients treated w/o additional stenting patients treated w/o additional stenting demonstrated a demonstrated a restenosis rate of 5.5%restenosis rate of 5.5%

The The PPaclitaxel-aclitaxel-EEluting luting PPTCA-TCA-Balloon Catheter in Balloon Catheter in CCoronary oronary

AArtery rtery DDiseaseisease



The The PPaclitaxel-aclitaxel-EEluting luting PPTCA-TCA-Balloon Catheter in Balloon Catheter in CCoronary oronary

AArtery rtery DDiseaseisease



Event Free Survival (ITT/AsT)Event Free Survival (ITT/AsT)

70

75

80

85

90

95

100

0 2 4 6 8 10

Sub

ject

s [%

]

DES/ I TT DEB/ I TT

DES/AsT DEB/AsT

p=0.07

p=0.007

Months post PCI

Outcome (AsT: N=126)DEB (N=66)DEB (N=66) DES (N=60)DES (N=60) P=P=

Follow-up:clinical[months]Follow-up:clinical[months] 6.2 ± 0.86.2 ± 0.8 6.2 ± 0.86.2 ± 0.8 0.70.7

Follow-up: clinical [N]Follow-up: clinical [N] 64 (97.0%)64 (97.0%) 60 (100%)60 (100%) 0.40.4

Follow-up: angiographicFollow-up: angiographic 58 (87.9%)58 (87.9%) 54 (90.0%)54 (90.0%) 0.80.8

Late lumen loss [mm]Late lumen loss [mm] 0.19 ± 0.380.19 ± 0.38 0.47 ± 0.710.47 ± 0.71 0.030.03

Binary restenosis insegmentBinary restenosis insegment 2/58 2/58 (3.4%)(3.4%) 11/54 11/54 (20.4%)(20.4%) 0.0070.007

TLRTLR 2/64 (3.1%)2/64 (3.1%) 10/60 (16.7%)10/60 (16.7%) 0.020.02

Myocardial infarctionMyocardial infarction 0/64 (0.0%)0/64 (0.0%) ff1/60 (1.7%)1/60 (1.7%) 11

DeathDeath *2/64 (3.1%)*2/64 (3.1%) **1/60 (1.7%)**1/60 (1.7%) 11

Total MACE Total MACE (w/o noncardiac death)(w/o noncardiac death) 3/64 (4.7%)3/64 (4.7%) 11/60 (18.3%)11/60 (18.3%) 0.020.02

fNSTEMI due to side branch occlusion

*1 cardiac, not lesion related 2 non cardiac** non-cardiac death

The PEPCAD ProgramThe PEPCAD ProgramPaclitaxel-Eluting PTCA-Catheter in Coronary Artery DiseasePaclitaxel-Eluting PTCA-Catheter in Coronary Artery Disease

TitleTitle DesignDesign StatusStatus PIPI

PEPCAD I SVDPEPCAD I SVD Sequent in Sequent in ≤2.8mm, ≤2.8mm, 120px, multi-center, GER120px, multi-center, GER

6mo-FU 6mo-FU MU, CRIMU, CRI

PEPCAD II ISRPEPCAD II ISR Sequent vs Taxus in ISRSequent vs Taxus in ISR, , 131px, multi-center, GER131px, multi-center, GER

6mo-FU 6mo-FU MU, CRIMU, CRI

PEPCAD III PEPCAD III Sequent + pre-loaded Sequent + pre-loaded Coroflex Blue vs Cypher, Coroflex Blue vs Cypher, 600 px, Europe600 px, Europe

Q2/07 Q2/07 activeactive

B.SchellerB.Scheller

PEPCAD IV DMPEPCAD IV DM Sequent vs Taxus in DMSequent vs Taxus in DM, , 160px, multi-center, 160px, multi-center, Thailand, Malaysia Thailand, Malaysia

Q2/07 Q2/07 activeactive

D.Rosli, D.Rosli, MU, CRIMU, CRI

PEPCAD V BIFPEPCAD V BIF Sequent, 25px, dual-Sequent, 25px, dual-center, GERcenter, GER

Q3/ 07 Q3/ 07 activeactive

D.Mathey D.Mathey MU, MU, CRICRI

INDICORINDICOR Coroflex Blue+Sequent,Coroflex Blue+Sequent, Real World, 100pxReal World, 100px

PlanningPlanning U.Kaul, U.Kaul, MU, CRIMU, CRI

2007, The year in PCI2007, The year in PCIConclusionsConclusions

DESDES– Multiple registries of real world DES usage showing that as compared to BMSMultiple registries of real world DES usage showing that as compared to BMS

DES improve outcome, and do so safely. Reduced mortality in some registriesDES improve outcome, and do so safely. Reduced mortality in some registries Sustained reduction in TVR.Sustained reduction in TVR. Slight increase in ST beyond 6 months compensated by reduction in TVR.Slight increase in ST beyond 6 months compensated by reduction in TVR.

– New DES, New DES, Everolimus-Eluting XIENCE™ V stentEverolimus-Eluting XIENCE™ V stent Similar rates of ST, MI and deathSimilar rates of ST, MI and death Favorable reduction in late loss and TVR.Favorable reduction in late loss and TVR.

BivalirudinBivalirudin– When used during acute STEMI PCI as mono-therapy as compared to heparin + When used during acute STEMI PCI as mono-therapy as compared to heparin +

IIb/IIIa, IIb/IIIa, Reduced bleeding complication.Reduced bleeding complication. Similar MACESimilar MACE Reduce cardiac death. Reduce cardiac death.

PCI in stable CADPCI in stable CAD– Courage trial, PCI with BMS for stable CAD vs. aggressive medical rx. onlyCourage trial, PCI with BMS for stable CAD vs. aggressive medical rx. only

Similar mortalitySimilar mortality Similar outcome for composite death, MI, CVA, hospitalization for ACS.Similar outcome for composite death, MI, CVA, hospitalization for ACS. Reduced symptoms with decreased need for future revascularization.Reduced symptoms with decreased need for future revascularization. Nuclear sub study showed that patients with moderate to severe ischemia had nearly Nuclear sub study showed that patients with moderate to severe ischemia had nearly

50% reduction in death and MI.50% reduction in death and MI. Residual ischemia is a predictor of increased mortality.Residual ischemia is a predictor of increased mortality.

2007, The year in PCI2007, The year in PCIConclusionsConclusions

Acute MI PCIAcute MI PCI– Use of thrombus aspiration catheter prior to stentingUse of thrombus aspiration catheter prior to stenting

Improved myocardial blush gradeImproved myocardial blush grade Improved ST resolution and reduced persistent ST deviationImproved ST resolution and reduced persistent ST deviation With improved myocardial perfusion, reduced mortality and MACE.With improved myocardial perfusion, reduced mortality and MACE.

New Technology, DEBNew Technology, DEB– Paclitaxel eluting DEBPaclitaxel eluting DEB

was safe and associated with a high procedural success rate in ISR was safe and associated with a high procedural success rate in ISR exhibited low late lumen loss after 6 months in ISRexhibited low late lumen loss after 6 months in ISR was superior to the paclitaxel-eluting Taxuswas superior to the paclitaxel-eluting Taxus stent in ISR after 6 stent in ISR after 6

monthsmonths was not associated with late thrombosis in was not associated with late thrombosis in 250 patient years in 250 patient years in

ISRISR

2007, The Year in PCI Asad Pathan FACC FSCAI March 15 th, 2008.

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Transcript of 2007, The Year in PCI Asad Pathan FACC FSCAI March 15 th, 2008.