SPIDER Saphenous Vein Graft Protection In a Distal Embolic Protection Randomized Trial Simon R. Dixon MBChB, William W. O’Neill MD William Beaumont Hospital, on behalf on the SPIDER Investigators 18 October 2005 TCT 2005

SPIDER Objective To evaluate the safety and efficacy of the SPIDER™/SpideRX™ Embolic Protection Device during PCI of saphenous vein graft diseaseTo evaluate the safety and efficacy of the SPIDER™/SpideRX™ Embolic Protection Device during PCI of saphenous vein graft disease

SPIDER SPIDER Device 5 sizes (3.0 – 7.0mm) Heparin coated 6 or 7F guide catheter Delivery –Guidewire of choice –3.2F Delivery catheter –Rapid exchange system (SpideRX) Retrieval –4.2/4.9F catheter (SpideRX 4.2F) Caution: Investigational device. Limited by US Federal Law to investigational use. Nitinol Mesh Filter Retrieval

SPIDER Study Design 732 pts with SVG lesions 80 clinical sites from Feb 2003-July 2005 GuardWire or FilterWire (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 Criteria Evidence of myocardial ischemia De novo lesion,  50% stenosis TIMI flow  1 Diameter  3.0mm and  6.0mm  40mm proximal to distal anastomosis

SPIDER Major 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 Endpoints Primary EndpointPrimary Endpoint –MACE at 30-days = Death, MI* (Q-wave and non-Q wave), TVR, urgent CABG Secondary EndpointsSecondary Endpoints –Safety (In-hospital MACE, CK/CKMB elevation, major bleeding & vascular complications or stroke in-hospital or 30- days, and Device success) –Efficacy (Clinical & Procedural success) *Defined as CKMB >3x ULN

SPIDER Study Design and Analysis Non-Inferiority DesignNon-Inferiority Design Sample Size:Sample Size: –Expected event rate in each study arm 10.0% –Delta for equivalence = 5.5% –One sided  error = 0.05, Power 80% –732 evaluable patients to demonstrate non-inferiority Primary Endpoint Analysis: Intent-to-treatPrimary Endpoint Analysis: Intent-to-treat

SPIDER Study Organization Principal Investigator William W. O’Neill MD, William Beaumont Hospital Data Management Harvard Clinical Research Institute, Boston, MA. Angiographic Core Lab Brigham & Women’s Hospital, Boston, MA (Jeffrey Popma, MD) ECG Core Lab HCRI, Boston, MA Peter Zimetbaum MD Study Monitor Bailer Research Group, Lake Hopatcong, NJ Sponsor ev3, Plymouth, MN

SPIDER Top 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 Metzger MDWellmont Holston Valley Medical Center, Christopher Metzger 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 Characteristics SPIDERControlP-value Age (yrs) 68.8   Male82.5%81.0%0.64 Diabetes39.3%45.1%0.12 Hypertension88.2%88.5%1.00 Dyslipidemia91.4%92.9%0.50 Current smoker 12.1%11.2%0.73 Previous MI 59.4%53.0%0.09 CCS III/IV angina 55.0%53.7%1.00 LVEF (%) 48.7  

SPIDER Baseline Angiographic Data SPIDERControlP-value No. vessels treated SVG age (yrs) 11.2   Degeneration score 40.5   RVD (mm) 3.26   MLD (mm) 0.99   Diameter stenosis (%) 70   Lesion length 14.6   TIMI 3 flow 90.6%89.0%0.48 Thrombus grade  %14.4%0.76

SPIDER SVG Distribution SPIDER N=396 vessels Control N=379 vessels RCA Circumflex LAD P=NS 92.4% lesions proximal-mid90.1% lesions proximal-mid Other

SPIDER Procedural Results SPIDERControlP-value No. vessels treated Stent implantation 99.2%99.5%1.00 Stent length per lesion 25.1   IIbIIIa Inhibitor 30.3%29.4%0.81 MLD In-stent (mm) 3.09   DS In-stent (%) 4.9   TIMI 3 flow 98.0%98.1%1.00 Visible debris 63.5%61.9%0.72 No-reflow1.8%3.8%0.12 Distal embolization 1.0%0.5%0.69

SPIDER Secondary Endpoints SPIDERControlP-value Safety Device success* 94.0%95.9%0.25 In-hospital MACE 7.9%7.1%0.78 Transfusion2.1%1.6%0.79 Stroke0.5%0.5%1.00 Efficacy Clinical success** 86.7%89.0%0.37 Procedural success 91.6%93.1%0.49 *Device success=Successful delivery, operation and retrieval device **Clinical success=Device success with no in-hospital MACE

SPIDER Primary Endpoint: 30-Day MACE P=NS for all comparisons P = 0.79 for Superiority, P = for Non-Inferiority Intent-to-treat analysis

SPIDER 30-Day MACE In Other Studies 30-Day MACE In Other Studies Superiority Non-Inferiority GuardWire GW & FW GuardWireTriActivSPIDEREmboshieldFilterWire GuardWireTRAP

SPIDER Conclusion SPIDER trial demonstrated that distal protection with the SPIDER/SpideRX Embolic Protection Device during SVG intervention results in a similar rate of MACE at 30-days and secondary safety endpoints, compared to distal protection with the GuardWire and FilterWire devicesSPIDER trial demonstrated that distal protection with the SPIDER/SpideRX Embolic Protection Device during SVG intervention results in a similar rate of MACE at 30-days and secondary safety endpoints, compared to distal protection with the GuardWire and FilterWire devices