The SAFER Trial Evaluation of the Clinical Safety and Efficacy of the PercuSurge GuardWire in Saphenous Vein Graft Intervention As presented at TCT 2000 by: Donald S. Baim, MD FACC Harvard Medical School Brigham and Women’s Hospital “SVG Angioplasty Free of Emboli Randomized”

The average longevity of a vein graft is 8-10 years 40% of occlude 75% develop severe narrowing Vein graft atherosclerosis is diffuse and friable Intervention may cause distal embolization Embolization compromises the distal microcirculation Manifest as no-reflow (8-10%) and CK elevation (17-20%) Mortality of 3.4% at 30 days (14% with CK-MB > 3x normal) A device that could capture and remove embolic particles before they reach the myocardium could reduce these complications The SAFER Trial Background

The SAFER Trial PercuSurge GuardWire ® System 4 components: GuardWire ® EZ-Flator ™ MicroSeal ® AdapterExport ® catheter

A. Lesion crossed with GuardWire ® B. GuardWire ® balloon inflated and intervention performed under protection. Stent placed with single wire technique The SAFER Trial PercuSurge GuardWire ® System

C. Export ® Aspiration catheter removes emboli & thrombus with slow distal to proximal pullback D. GuardWire ® balloon deflated The SAFER Trial PercuSurge GuardWire ® System

The SAFER Trial Prior studies: Webb et al (JACC 34:461, 1999) single site study of 27 patients MACE - 3.7% SAFE (E. Grube, PI) 103 patient European study (7 sites) visible material removed in 95% of cases 81% of material is under 96 micron MACE % (3.9% non-Q) The randomized SAFER trial was designed as an 800 patient prospective randomized trial to determine if the GuardWire reduced the incidence of MACE compared to conventional, unprotected stenting

Study Coordination: Cardiovascular Data Analysis Center (CDAC) Boston, MA QCA Core Lab: Brigham and Women’s Angiographic Core Laboratory (CDAC) Boston, MA ECG Core Lab: Cardiovascular Data Analysis Center (CDAC) Boston, MA Study Monitoring: Bailer Monitoring Lake Hopatcong, NJ Sponsor: PercuSurge, Inc. Sunnyvale, CA The SAFER Trial Study Management

Primary endpoint: “Major Adverse Clinical Events” (MACE) during index hospitalization A combined clinical endpoint defined as death, Q wave or Non Q-Wave MI (CK-MB > 3x ULN), emergent bypass surgery, or repeat target vessel revascularization The SAFER Trial Study Design

Inclusion criteria Lesions (50-100%) in SVG 3-6 mm in diameter More than 5 mm from ostium; 20 mm from distal anastomosis At least TIMI 1 flow at baseline Exclusion criteria Ongoing MI with + CK-MB EF 2.5 unless on hemodialysis Planned use of atherectomy device Enrollment 551 patients at 47 sites The SAFER Trial Study Design

The SAFER Trial Baseline Demographics GuardWire (n=273) No GuardWire (n=278) Age (yrs) 68.2 (36, 90) 68.5 (45, 92) Male80.5%84.9% History Diabetes Mellitus31.9%35.3% Prior MI59.8%63.7% Prior CVA/TIA11.0%13.1% Worsening exertional40.1%39.9% CCS* III or IV74.8%74.6% Rest angina38.6%37.0% Triple vessel disease73.7%80.1% Ejection Fraction Mean 48.3%47.0%

The SAFER Trial Baseline Lesion Characteristics GuardWire No GuardWire Pre RVD (mm) 3.45 (1.99, 5.73)3.47 (1.94, 5.99) MLD (mm) 1.08 (0.00, 3.58)1.05 (0.00, 3.08) Diameter Stenosis (%)69.0% 70.1% Lesion Length15.83 (2.16, 76.99)17.43 (3.00, 79.29) Target Vessel SVG-LAD19.7%17% SVG-LCX42.8%41.3% SVG-RCA37.1%41.7% Thrombus38.6%38.4% Eccentric Lesion37.6%34.1% Angulation >45% 6.5% 6.2%

The SAFER Trial Technical Success was defined as successful delivery of the GuardWire to the intended target site, inflation of the occlusion balloon, aspiration using the Export catheter and balloon deflation according to the Instructions For Use Procedure Success was defined as achievement of a final DS < 50% with no in- hospital MACE GuardWire No GuardWire Technical Success93.0% n/a Procedure success90.5%82.0% Number of stents Inflation time ~ 4 minutes, preliminary observation ~ 2% intolerant

GuardWire No GuardWire (273 Pts) (278 Pts) All Myocardial Infarction 8.4% 16.5% - Q Wave MI 1.1% 2.2% - Non Q-Wave MI 7.3% 14.4% Death 0.7% 1.1% Emergent CABG 0.0% 0.7% TLR 0.4% 0.7% Index Hospitalization 8.8% 17.3% p=.001 The SAFER Trial Results: Primary Endpoint

The SAFER Trial Results: MACE  50% (p<0.001)  50% (p<0.001) Percent Incidence

The SAFER Trial Results: Secondary Endpoints Post-Procedure TIMI Flow: GuardWire No GuardWire p-value TIMI 0, 1 1.5% 0.7% TIMI 2 0.4% 5.1% TIMI % 94.2% No-reflow 3.4% 8.0% Perforation 0.4% 1.4% Dissection 1.9% 1.1% Subac. Closure 0.7% 0.7%

The SAFER Trial GP IIb/IIIa Use GP IIb/IIIa inhibitor were used in >60% in both arms, mostly before intervention PercuSurge had MACE benefit with or without them GuardWire No Guardwire p IIb/IIIa (164 – 182) 11.6% 21.6% No IIb/IIIa (109 – 96) % 0.17 Why? GP IIb/IIIa’s prevent platelet thrombi, but they do not dissolve atherosclerotic plaque.

The SAFER Trial Conclusions The PercuSurge GuardWire ® system proved safe and effective in recovering potentially embolic material preserving normal flow and reducing MACE by 50% during the percutaneous interventional treatment of saphenous vein bypass grafts This underscores the importance of distal embolization protection in SVG intervention