A-F Vascular Protection in High-Risk Non-ST Elevation Acute Coronary Syndromes A ngioplasty B alloon-associated C oronary D ebris and the E Z F ilterWire M Webster M Webster Auckland City Hospital Auckland City Hospital Auckland, NZ on behalf of R Whitbourn, D McClean, C Juergens, H Lowe, G Barbeau x, P Matsis, D Walters, G Devlin, W Hui, D Brieger, G Tully xx and the A-F Investigators x – speaker’s honoraria, xx – BSC employee

A-F Study Centres Canada 3 Australia 7 New Zealand 4 Data Coordinating Centre ECG Core Laboratory HCRI, Boston, USA Angiographic Core Laboratory CRF, New York, USA Pathology Core Laboratory Concord Hospital Sydney, Australia Sponsor: Boston Scientific, Mountain View, CA, USA

A-F Enrolling Centers Center PI Patients Center PI Patients St Vincent’s, Melbourne R. Whitbourn32 St Vincent’s, Melbourne R. Whitbourn32 Auckland City, Auckland M. Webster29 Auckland City, Auckland M. Webster29 Christchurch, Christchurch D. McClean21 Christchurch, Christchurch D. McClean21 Liverpool, Sydney C. Juergens20 Liverpool, Sydney C. Juergens20 Laval, Quebec G. Barbeau 9 Laval, Quebec G. Barbeau 9 Wellington, Wellington P. Matsis 8 Wellington, Wellington P. Matsis 8 Prince Charles, Brisbane D. Walters 8 Prince Charles, Brisbane D. Walters 8 Waikato, Hamilton G. Devlin 6 Waikato, Hamilton G. Devlin 6 Royal Alexandra, Edmonton W. Hui 6 Royal Alexandra, Edmonton W. Hui 6 Concord, Sydney D. Brieger 4 Concord, Sydney D. Brieger 4 Box Hill, Melbourne G. New 3 Box Hill, Melbourne G. New 3 Prince of Wales, Sydney N. Jepson 2 Prince of Wales, Sydney N. Jepson 2 CHUM, Montreal F. Reeves 2 CHUM, Montreal F. Reeves 2 John Hunter, Newcastle S. Thambar 1 John Hunter, Newcastle S. Thambar 1

A-F Native Vessel Coronary Artery Disease Vein Graft Disease Stable Angina ST Elevation MI Non-ST Elevation Acute Coronary Syndromes

A-F Study Design Prospective, multicenter, unblinded, two-arm, randomized trial Selected high-risk patients with nonSTEMI acute coronary syndromes PCI using the BSC FilterWire EZ vs standard PCI without FilterWire EZ 150 patient pilot for pivotal protocol Provision for two additional cohorts - up to 450 patients

A-F FilterWire EZ mm & mm

A-F Study Population Non ST elevation ACS with "high risk" clinical features during 24 hours prior to angiography elevated troponin angina at rest dynamic ST or T wave changes (not ST elevation MI) Culprit lesion with "high risk" angiographic features (2 or more of the following) intra-coronary filling deficit consistent with thrombus lesion ulceration eccentric shape irregular or scalloped border abrupt edges to the lesion lesion length >20 mm

A-F

Primary Endpoint In-hospital MACE In-hospital MACE - death, recurrent myocardial infarction (CK-MB>3x normal), emergency CABG, repeat target vessel revascularisation

A-F Secondary Endpoints MACE at 30 days MACE at 30 days Change in CK-MB 6-24hours post-PCI Change in CK-MB 6-24hours post-PCI Change in troponin T 6-24 hours post-PCI Change in troponin T 6-24 hours post-PCI Device success – FilterWire EZ Device success – FilterWire EZ Incidence of embolic recovery Incidence of embolic recovery TIMI flow post-PCI TIMI flow post-PCI

A-F Baseline Characteristics FilterWire EZ Control FilterWire EZ Control Patients, n 7774 Age, mean (sd) 58(11)60(13) Male, % 8389 European, % 8888 Previous angina, % 4042 Diabetes, % 1626 Smoker – never, % 2934 Hypertension, % 3946 Dyslipidemia, % 6962

A-F Baseline Angiographic Findings FilterWire EZ Control FilterWire EZ Control Reference vessel, mm3.1(0.6)3.1(0.6) Diameter stenosis, %78(14)76(12) Lesion location - RCA,LAD,LCX,%37,39,2444,32,25 Lesion length, mm15.8(7.6)16.8(10.2) Lesion ulceration, % Lesion calcification - mod/severe, %29 34 TIMI III flow, %60 67

A-F Primary Endpoint p=0.793

A-F Secondary Endpoints FilterWire EZ Control FilterWire EZ Control MACE 30 day, % Change CK-MB 5.1(20)4.1(6) Change troponin T 0.4(0.7)0.4(0.6) Device success, % 97 n/a Embolic recovery, % 42 n/a Post-PCI TIMI III, % 94 94

A-F Subset Analyses No difference between FilterWire EZ and control groups in: Patient treated with planned glycoprotein IIb/IIIa inhibitors Diabetic patients Patients pre-treated with clopidogrel Patients with prior thrombolytic therapy

A-F Why Was There No Benefit With FilterWire? Wrong patho-physiology? Wrong patho-physiology? embolism occurs during PCI for nonSTEMI - histology, thrombectomy, MRI Wrong lesions selected? Wrong lesions selected? only 42% had emboli captured calcified vs thrombotic lesions Incomplete protection? Incomplete protection? embolism with positioning the device filter mouth/ vessel wall apposition incomplete side branch protection small particle embolism Insufficient study population? Insufficient study population? - type II error

A-F

Summary A-F is the only randomised trial of a vascular protection device undertaken in non-STEMI acute coronary syndrome patients A-F is the only randomised trial of a vascular protection device undertaken in non-STEMI acute coronary syndrome patients No difference between FilterWire EZ and control groups in in-hospital MACE or post-procedure CK-MB or troponin elevation No difference between FilterWire EZ and control groups in in-hospital MACE or post-procedure CK-MB or troponin elevation Routine use of vascular protection devices in such patients does not appear warranted Routine use of vascular protection devices in such patients does not appear warranted - further angiographic analysis may reveal sub- groups at particular risk for embolism