SPIDERSPIDERSSaphenous Vein Graft aphenous Vein Graft PProtection rotection

IIn a n a DDistal istal EEmbolic Protection mbolic Protection RRandomized Trialandomized Trial

Simon R. DixonSimon R. Dixon MBChB, William W. O’Neill MD MBChB, William W. O’Neill MD

William Beaumont Hospital,William Beaumont Hospital,

on behalf on the SPIDER Investigatorson behalf on the SPIDER Investigators

18 October 2005

TCT 2005

SPIDER

ObjectiveObjective

• To evaluate the To evaluate the safetysafety and and efficacyefficacy of the of the SPIDERSPIDER™™/SpideRX/SpideRX™™ Embolic Protection Embolic Protection Device during PCI of saphenous vein Device during PCI of saphenous vein graft diseasegraft disease

SPIDER

SPIDER DeviceSPIDER Device

• 5 sizes (3.0 – 7.0mm)5 sizes (3.0 – 7.0mm)• Heparin coatedHeparin coated• 6 or 7F guide catheter6 or 7F guide catheter• DeliveryDelivery

– Guidewire of choiceGuidewire of choice– 3.2F Delivery catheter3.2F Delivery catheter

– Rapid exchange Rapid exchange system (SpideRX)system (SpideRX)

• RetrievalRetrieval– 4.2/4.9F catheter 4.2/4.9F catheter

(SpideRX 4.2F)(SpideRX 4.2F)

Caution: Investigational device. Limited by US Federal Law to investigational use.

Nitinol Mesh Filter

RetrievalRetrieval

SPIDER

Study DesignStudy Design

732 pts with SVG lesions80 clinical sites from Feb 2003-July 2005

GuardWire orFilterWire (EX/EZ*)

N=357

SPIDER/SpideRX*N=375

Randomization stratified by planned IIbIIIa use

ASA & Plavix

Non-Inferiority Analysis

SpideRX & FilterWire EZ introduced Nov 2004

(76% FilterWire)(30% SpideRX)

SPIDER

Major Inclusion CriteriaMajor Inclusion Criteria

Evidence of myocardial ischemiaEvidence of myocardial ischemia

De novo lesion, De novo lesion, 50% stenosis50% stenosisTIMI flow TIMI flow 11

Diameter Diameter 3.0mm and 3.0mm and 6.0mm6.0mm

40mm proximal to distal 40mm proximal to distal anastomosisanastomosis

SPIDER

Major Exclusion CriteriaMajor Exclusion Criteria

• Recent AMI with elevated baseline CK/CKMBRecent AMI with elevated baseline CK/CKMB• LVEF <25%LVEF <25%• SVG <6-months oldSVG <6-months old• TIMI 0 FlowTIMI 0 Flow• Arterial conduitArterial conduit• Planned atherectomyPlanned atherectomy• Creatinine >2.5mg/dLCreatinine >2.5mg/dL• TIA or stroke within 60-daysTIA or stroke within 60-days

SPIDER

Study EndpointsStudy Endpoints

• Primary EndpointPrimary Endpoint– MACE at 30-days MACE at 30-days = D= Death, MI* (Q-wave and eath, MI* (Q-wave and

non-Q wave), TVR, urgent CABGnon-Q wave), TVR, urgent CABG

• Secondary EndpointsSecondary Endpoints– SafetySafety (In-hospital MACE, CK/CKMB (In-hospital MACE, CK/CKMB

elevation, major bleeding & vascular elevation, major bleeding & vascular complications or stroke in-hospital or 30-complications or stroke in-hospital or 30-days, and Device success)days, and Device success)

– EfficacyEfficacy (Clinical & Procedural success) (Clinical & Procedural success)

*Defined as CKMB >3x ULN

SPIDER

Study Design and AnalysisStudy Design and Analysis

• Non-Inferiority DesignNon-Inferiority Design

• Sample SizeSample Size::– Expected event rate in each study arm 10.0%Expected event rate in each study arm 10.0%– Delta for equivalence = 5.5%Delta for equivalence = 5.5%– One sided One sided error = 0.05, Power 80% error = 0.05, Power 80%– 732 evaluable patients to demonstrate non-inferiority732 evaluable patients to demonstrate non-inferiority

• Primary Endpoint Analysis: Intent-to-treatPrimary Endpoint Analysis: Intent-to-treat

SPIDER

Study OrganizationStudy Organization

Principal InvestigatorPrincipal Investigator William W. O’Neill MD, William W. O’Neill MD, William Beaumont HospitalWilliam Beaumont Hospital

Data ManagementData Management Harvard Clinical Research Harvard Clinical Research Institute, Boston, MA.Institute, Boston, MA.

Angiographic Core LabAngiographic Core Lab Brigham & Women’s Hospital, Brigham & Women’s Hospital, Boston, MA (Jeffrey Popma, MD)Boston, MA (Jeffrey Popma, MD)

ECG Core LabECG Core Lab HCRI, Boston, MA HCRI, Boston, MA Peter Zimetbaum MD Peter Zimetbaum MD

Study MonitorStudy Monitor Bailer Research Group, Bailer Research Group, Lake Hopatcong, NJLake Hopatcong, NJ

SponsorSponsor ev3, Plymouth, MNev3, Plymouth, MN

SPIDER

Top Ten EnrollersTop Ten Enrollers

• Munroe Regional Medical Center, Robert Feldman MDMunroe Regional Medical Center, Robert Feldman MD

• William Beaumont Hospital, William O’Neill MDWilliam Beaumont Hospital, William O’Neill MD

• Moses Cone Hospital, Thomas Stuckey MDMoses Cone Hospital, Thomas Stuckey MD

• Peninsula Cardiology Associates, Frank Arena MDPeninsula Cardiology Associates, Frank Arena MD

• St. Vincent Health Center, Jack Smith MDSt. Vincent Health Center, Jack Smith MD

• Our Lady of Lourdes Medical Center, Randy Mintz MDOur Lady of Lourdes Medical Center, Randy Mintz MD

• Wellmont Holston Valley Medical Center, Christopher Wellmont Holston Valley Medical Center, Christopher Metzger MDMetzger MD

• Washington Adventist Hospital, Mark Turco MDWashington Adventist Hospital, Mark Turco MD

• Wake Heart Associates, J. Tift Mann, MDWake Heart Associates, J. Tift Mann, MD

• Tallahassee Memorial Hospital, John Katopodis, MDTallahassee Memorial Hospital, John Katopodis, MD

SPIDER

Clinical CharacteristicsClinical Characteristics

SPIDERSPIDER ControlControl P-valueP-value

Age (yrs)Age (yrs) 68.8 68.8 10.2 10.2 69.6 69.6 9.4 9.4 0.270.27

MaleMale 82.5%82.5% 81.0%81.0% 0.640.64

DiabetesDiabetes 39.3%39.3% 45.1%45.1% 0.120.12

HypertensionHypertension 88.2%88.2% 88.5%88.5% 1.001.00

DyslipidemiaDyslipidemia 91.4%91.4% 92.9%92.9% 0.500.50

Current smokerCurrent smoker 12.1%12.1% 11.2%11.2% 0.730.73

Previous MIPrevious MI 59.4%59.4% 53.0%53.0% 0.090.09

CCS III/IV anginaCCS III/IV angina 55.0%55.0% 53.7%53.7% 1.001.00

LVEF (%)LVEF (%) 48.7 48.7 12.2 12.2 48.8 48.8 12.1 12.1 0.930.93

SPIDER

Baseline Angiographic DataBaseline Angiographic Data

SPIDERSPIDER ControlControl P-valueP-value

No. vessels treatedNo. vessels treated 396396 379379

SVG age (yrs)SVG age (yrs) 11.2 11.2 5.7 5.7 11.7 11.7 5.8 5.8 0.290.29

Degeneration scoreDegeneration score 40.5 40.5 21.6 21.6 40.6 40.6 20.7 20.7 0.960.96

RVD (mm)RVD (mm) 3.26 3.26 0.67 0.67 3.34 3.34 0.63 0.63 0.080.08

MLD (mm)MLD (mm) 0.99 0.99 0.50 0.50 1.04 1.04 0.48 0.48 0.120.12

Diameter stenosis (%)Diameter stenosis (%) 70 70 12 12 69 69 12 12 0.260.26

Lesion lengthLesion length 14.6 14.6 10.1 10.1 14.4 14.4 9.6 9.6 0.770.77

TIMI 3 flowTIMI 3 flow 90.6%90.6% 89.0%89.0% 0.480.48

Thrombus grade Thrombus grade 33 15.5%15.5% 14.4%14.4% 0.760.76

SPIDER

SVG DistributionSVG Distribution

SPIDERN=396 vessels

ControlN=379 vessels

18.2% 0.3%

39.0%42.5%

16.0%

43.9%40.1%

RCA RCACircumflex Circumflex

LAD LAD

P=NS

92.4% lesions proximal-mid 90.1% lesions proximal-mid

Other

SPIDER

Procedural ResultsProcedural Results

SPIDERSPIDER ControlControl P-valueP-value

No. vessels treatedNo. vessels treated 396396 379379

Stent implantationStent implantation 99.2%99.2% 99.5%99.5% 1.001.00

Stent length per lesionStent length per lesion 25.1 25.1 13.4 13.4 26.9 26.9 14.5 14.5 0.080.08

IIbIIIa Inhibitor IIbIIIa Inhibitor 30.3%30.3% 29.4%29.4% 0.810.81

MLD In-stent (mm)MLD In-stent (mm) 3.09 3.09 0.58 0.58 3.11 3.11 0.58 0.58 0.760.76

DS In-stent (%)DS In-stent (%) 4.9 4.9 10.9 10.9 6.7 6.7 12.3 12.3 0.030.03

TIMI 3 flowTIMI 3 flow 98.0%98.0% 98.1%98.1% 1.001.00

Visible debrisVisible debris 63.5%63.5% 61.9%61.9% 0.720.72

No-reflowNo-reflow 1.8%1.8% 3.8%3.8% 0.120.12

Distal embolizationDistal embolization 1.0%1.0% 0.5%0.5% 0.690.69

SPIDER

Secondary EndpointsSecondary Endpoints

SPIDER SPIDER ControlControl P-valueP-value

SafetySafety

Device success* Device success* 94.0%94.0% 95.9%95.9% 0.250.25

In-hospital MACEIn-hospital MACE 7.9%7.9% 7.1%7.1% 0.780.78

TransfusionTransfusion 2.1%2.1% 1.6%1.6% 0.790.79

StrokeStroke 0.5%0.5% 0.5%0.5% 1.001.00

EfficacyEfficacy

Clinical success** Clinical success** 86.7%86.7% 89.0%89.0% 0.370.37

Procedural successProcedural success 91.6%91.6% 93.1%93.1% 0.490.49

*Device success=Successful delivery, operation and retrieval device**Clinical success=Device success with no in-hospital MACE

SPIDER

Primary Endpoint: 30-Day MACEPrimary Endpoint: 30-Day MACE

0.3

8.5

1.1

7.7

1.1

9.1

0.6

7.6

0.6

7.0

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8.4

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8

12

Death MI Q-wave MI Non-Q MI TVR MACE

Inc

ide

nc

e (

%)

SPIDER N=375Control N=357

P=NS for all comparisonsP=NS for all comparisons

P = 0.79P = 0.79 for Superiority,for Superiority, P = 0.012 for Non-Inferiority P = 0.012 for Non-Inferiority

Intent-to-treat analysis

SPIDER

30-Day MACE In Other Studies30-Day MACE In Other Studies

16.517.3

11.6

9.110.1

8.49.6

12.7

9.911.4 11.2

9.1

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10

15

20

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SPIDER

ConclusionConclusion

• SPIDER trial demonstrated that distal SPIDER trial demonstrated that distal

protection with the protection with the SPIDER/SpideRX SPIDER/SpideRX

Embolic Protection Device Embolic Protection Device during SVG during SVG

interventionintervention results in a similar rate of results in a similar rate of

MACE at 30-days and secondary safety MACE at 30-days and secondary safety

endpointsendpoints, compared to distal protection , compared to distal protection

with the GuardWire and FilterWire deviceswith the GuardWire and FilterWire devices