The SPIRIT II Study - A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary

The SPIRIT II Study - A Clinical Evaluation of the XIENCE™ V Everolimus Eluting Coronary Stent

System in the Treatment of Patients With De Novo Native Coronary Artery Lesions

Clinical, Angiographic and IVUS 2 year results

Patrick W. Serruys, MD, PhD

Thoraxcenter, Erasmus Medical Center, Rotterdam,the Netherlands

SCAI-ACCi2 Late-Breaking Clinical Trials III: DES

Monday March 31st, 2008 8.45 amProfessor Serruys has no conflict of interest related to this presentation

SE2926406 REV ACAUTION: XIENCE™ V is an Investigational device. Limited by Federal (U.S.) law to investigational use only.TAXUS® Paclitaxel-eluting Coronary Stent System is a registered trademark of Boston Scientific or its affiliates.

SPIRIT II Clinical, Angiographic and IVUS2 Year Results

Patrick W. Serruys on behalf of

Germany: J. Neuzner J. Schofer M. Wiemer G. Richardt M. Desaga

The Netherlands: J. Piek H. Suryapranata M. Suttorp J.A.M. te Riele

France: D. Carrie J. Berland C. Spaulding

Denmark: L. Thuesen H. Kelbaek K. Rasmussen

New Zealand: P. Ruygrok India: A. Seth Switzerland: E. Camenzind Spain: C. Macaya

E. Garcia Belgium: F. Van den Branden

V. Legrand J. Boland

Poland: W. Ruzyllo Italy: A. Manari Austria: K. Huber


Study Design

Prospective, randomized (3:1), single-blind, non-inferiority to TAXUS®

Primary endpoint: Angiographic in-stent late loss at 180 days (powered for sequential non-inferiority and superiority)

Secondary endpoint: Angiographic in-segment late loss at 180 days (powered for non-inferiority)

Clinical follow-up: 30, 180, 270 days, 1, 2, 3, 4 and 5 years. Angiographic and IVUS follow-up: baseline, 180 days & 2 years (only for 152 patients)

3: 1

Maximum two de novo lesions

300 patients

2.5 – 4.0 mmn = 300

XIENCE™ Vn = 223

TAXUS®n = 77

Sponsor: Abbott Vascular

PI: PW Serruys MD, PhD

SC: E Garcia MD, J Ormiston MD, M Wiemer MD

DSMB: J Tijssen PhD, T Lefèvre MD, P Urban MD

CEC: C Hanet MD, D McClean MD, V Umans MD

Angiographic and IVUS Corelab: Cardialysis (Rotterdam, NL)

SE2926406 REV A

CAUTION: XIENCE™ V is an Investigational device. Limited by Federal (U.S.) law to investigational use only.TAXUS® Paclitaxel-eluting Coronary Stent System is a registered trademark of Boston Scientific or its affiliates.

n = 300

n = 223 n = 77

n = 211 n = 73

XIENCE™ V TAXUS®

n = 85nL = 100

n = 32nL = 35

2 Year

QCA

2 Year

Clinical

nL: number of lesions

Clinical Study Population

n = 72nL = 78

n = 31nL =32

2 Year

IVUS

Angiographic and IVUSSubgroup*

-7 non-cardiac deaths-1 withdrawn at 30 days-3 withdrawn at 1 year-1 lost to FU

-4 non-cardiac deaths


*Total angiographic and IVUS subgroup: 152 patients (113 XIENCETM V, 39 TAXUS®)Angiographic follow-up at 2-year follow-up: XIENCE™ V: 75%; TAXUS®: 82% IVUS follow-up at 2-year follow-up: XIENCE™ V: 64%; TAXUS®: 79%

n = 300

n = 223 n = 77

n = 211 n = 73

XIENCE™ V TAXUS®

n = 85nL = 100

n = 32nL = 35

2 Year

QCA

2 Year

Clinical



n = 72nL = 78

n = 31nL =32

2 Year

IVUS*Total angiographic and IVUS subgroup: 152 patients (113 XIENCETM V, 39 TAXUS®)Angiographic follow-up at 2-year follow-up: XIENCE™ V: 75%; TAXUS®: 82% IVUS follow-up at 2-year follow-up: XIENCE™ V: 64%; TAXUS®: 79%

-3 deaths-19 refused angio/IVUS-1 withdrawn at 30 days-3 withdrawn at 1 year-2 medical decisions

-4 deaths-1 angio not required (did not receive study stent)- 2 refused angio/IVUS


n = 300

n = 223 n = 77

n = 211 n = 73

XIENCE™ V TAXUS®

n = 85nL = 100

n = 32nL = 35

2 Year

QCA

2 Year

Clinical



n = 72nL = 78

n = 31nL =32

2 Year

IVUS*Total angiographic and IVUS subgroup: 152 patients (113 XIENCETM V, 39 TAXUS®)Angiographic follow-up at 2-year follow-up: XIENCE™ V: 75%; TAXUS®: 82% IVUS follow-up at 2-year follow-up: XIENCE™ V: 64%; TAXUS®: 79%

-3 deaths-19 refused angio/IVUS-1 withdrawn at 30 days-3 withdrawn at 1 year-5 IVUS catheter did not cross-4 pullback issues-2 medical decision-1 patient in another hospital-2 technical problem-1 TLR but no IVUS done

-4 deaths-1 angio not required (did not receive study stent)-2 refused angio/IVUS-1 IVUS catheter did not cross


Baseline Demographics

ITTPatients with 6 month

& 2 year Angio/IVUS FU

XIENCE™ V 223 pts

TAXUS® 77

pts

XIENCE™ V 113 pts

TAXUS® 39 pts

Male (%) 71 79 73 82

Mean age (years) 62 62 62 62

Previous MI (%) 35 25 42* 18*

Prior inter. at target vessel (%) 4 4 5 3

Diabetes mellitus (%) 23 24 22 24

Insulin-dependent diabetes (%) 5 7 4 8

Hyperlipidemia req. med. (%) 69 75 75 77

Hypertension req. med.(%) 67 65 61 51

Current smoker (%) 32 30 32 32

*p=0.007


Baseline Angiography

ITTPatients with 6 month &

2 year Angio/IVUS FU

XIENCE™ V 260 lesions

TAXUS® 91 lesions

XIENCE™ V 132 lesions

TAXUS® 45 lesions

Dual Lesions Treated (%) 17 18 17 15

Type B2/C Lesions 78 80 76 77

Lesion Location

LAD 41 47 43 58

LCX 29* 19* 27** 13**

RCA 30 34 30 29

QCA

RVD (mm) 2.70* 2.82* 2.67** 2.86**

MLD (mm) 1.06* 1.14* 0.98** 1.13**

% DS

Lesion Length (mm)

Acute Gain (mm)

61

13.0

1.43

59

13.2

1.48

63

13.3

1.52

60

13.8

1.53*LCX p=0.072, RVD p = 0.099, MLD p=0.033.**LCX p=0.1, RVD p = 0.061, MLD p=0.013.


0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

-0.75 -0.5 -0.25 0 0.25 0.5 0.75 1 1.25 1.5 1.75 2

In-stent Late Loss (mm)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

-0.75 -0.5 -0.25 0 0.25 0.5 0.75 1 1.25 1.5 1.75 2

In-stent Late Loss (mm)

% o

f Les

ions

In-stent Late Loss in Patientswith Serial 6 Month and 2 Year Angio FU

6 Months 2 Years

XIENCE V

XIENCETM V

TAXUS®*XIENCETM V

TAXUS®+

XIENCETM V: 0.17 ± 0.32 (nL=97)

TAXUS®: 0.33 ± 0.32 (nL=35)

P=0.0037

XIENCETM V: 0.33 ± 0.37 (nL=97)

TAXUS®: 0.34 ± 0.34 (nL=35)

P=0.6026

In this serial analysis, for patients having TLR, values of loss and neo-intimal hyperplasia observed prior to 6 month or 2 year FU were imputed at 6 months and 2 years respectively


In-Stent % Diameter Stenosis in Patientswith Serial 6 Month and 2 Year Angio FU

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

-20% 0% 20% 40% 60% 80% 100%

In-stent % Diameter Stenosis

6 Months

TAXUS

XIENCETM V

TAXUS®*

XIENCETM V: 16.0% ± 11.4% (nL=97)

TAXUS® : 18.3% ± 10.6% (nL=35)

XIENCETM V: 19.2% ± 13.9% (nL=97)

TAXUS® : 18.8% ± 11.4% (nL=35)


P = 0.0620 P = 0.9589

SE2926406 REV A

2 Years

XIENCETM V

TAXUS®+

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0% 20% 40% 60% 80% 100%

In-segment % Diameter Stenosis


Angiographic Binary Restenosis in Patientswith Serial 6 Month and 2 Year Angio FU

1.0%

3.1%2.9%

5.7%

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

10%

In-stent ABR In-segment ABR

XIENCETM V (nL = 97)TAXUS® (nL = 35)

6 Months 2 Years

2.1%

5.2%

2.9%

8.6%

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

10%

In-stent ABR In-segment ABR


P = 0.4615

P = 0.6079

P = 1.0000

P = 0.4400



2.8

6.5

0

1

2

3

4

5

6

7

% VO

IVUS in Patients with Serial 6 Monthand 2 Year IVUS FU

6 Months 2 Years

12.6

4.1

0

2

4

6

8

10

12

14

NIH

11.6

8.4

0

2

4

6

8

10

12

14

NIH

mm3 mm3

5.25.8

0

1

2

3

4

5

6

7

% VO

P=0.0009 P=0.0007

In this serial analysis, for patients having TLR, values of loss and neo-intimal hyperplasiaobserved prior to 6 month or 2 year FU were imputed at 6 months and 2 years respectively XIENCETM V (nL = 69)

TAXUS® (nL = 32)

P = 0.2527 P = 0.4026

SE2926406 REV A

ARC Stent Thrombosis

Definite and Probable XIENCE™ V

223 patients

TAXUS ®

77 patients

Acute stent thrombosis (%) 0.0 0.0

Sub-acute stent thrombosis (%) 0.0 1.3

220 patients 77 patients

Late stent thrombosis (%) 0.0 1.3

211 patients 73 patients

Very late stent thrombosis (%) 0.9 0.0

Total stent thrombosis (%) 0.9 1.4

Acute: 0 to 24 hours after stent implantation Subacute: >24 hours to 30 days after stent implantationLate: >30 days to 1 year after stent implantation Very late: >1 year after stent implantation

SE2926406 REV A

p=NS


2 Year Clinical Results

HierarchicalXIENCE™ V

211 patients

TAXUS ®

73 patientsCardiac death % 0.5 1.4

Myocardial infarction %

Q-wave MI

Non Q-wave MI

0

2.8

0

4.1

Ischemia driven TLR %

CABG

PCI

0

3.3

0

5.5

MACE % 6.6 11.0

Ischemia driven TLR % 3.8 6.8

Non-ischemia driven TLR % 1.4 3.9

Total TLR % 4.6 9.1

MACE: cardiac death, MI, ID-TLR by CABG or PCI

Non-hierarchicalXIENCE™ V

218 patients

TAXUS ®

77 patients


6 Months (6M) and 2 Year (2Y)Clinical Results

1


Conclusions

• SPIRIT II 2 year data shows a consistent reduction in clinical events for XIENCE™ V vs TAXUS® (MACE 6.6% vs 11.0%)

• Low stent thrombosis rate for XIENCE ™ V at 2 years (0.9 % XIENCE ™ V vs 1.4% TAXUS® )

XIENCE™ V remains numerically lower than TAXUS® in MACE and all it's components at 2 year follow-up, despite a modest increase in late loss and neo-intima in the XIENCE ™ V arm over time.


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The SPIRIT II Study - A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary