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Vascular Protection in High-Risk Non-ST Elevation Acute Coronary Syndromes

Angioplasty Balloon-associated Coronary Debris and the EZ FilterWire

M WebsterM Webster Auckland City HospitalAuckland City Hospital

Auckland, NZAuckland, NZ

on behalf of R Whitbourn, D McClean, C Juergens, on behalf of R Whitbourn, D McClean, C Juergens, H Lowe, G BarbeauH Lowe, G Barbeauxx

, P Matsis, D Walters, G , P Matsis, D Walters, G Devlin, W Hui, D Brieger, G TullyDevlin, W Hui, D Brieger, G Tullyxxxx

and the A-F and the A-F InvestigatorsInvestigators

x – speaker’s honoraria, xx – BSC employeex – speaker’s honoraria, xx – BSC employee

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Study Centres

Canada 3

Australia 7

New Zealand 4

Data Coordinating CentreECG Core LaboratoryHCRI, Boston, USA

Angiographic Core LaboratoryCRF, New York, USA

Pathology Core LaboratoryConcord Hospital Sydney, Australia

Sponsor: Boston Scientific, Mountain View, CA, USA

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Enrolling Centers CenterCenter PI PI Patients Patients

St Vincent’s, MelbourneSt Vincent’s, Melbourne R. Whitbourn R. Whitbourn 3232 Auckland City, AucklandAuckland City, Auckland M. Webster M. Webster 2929 Christchurch, ChristchurchChristchurch, Christchurch D. McClean D. McClean 2121 Liverpool, SydneyLiverpool, Sydney C. Juergens C. Juergens 2020 Laval, QuebecLaval, Quebec G. Barbeau G. Barbeau 9 9 Wellington, WellingtonWellington, Wellington P. Matsis P. Matsis 8 8 Prince Charles, BrisbanePrince Charles, Brisbane D. Walters D. Walters 8 8 Waikato, HamiltonWaikato, Hamilton G. Devlin G. Devlin 6 6 Royal Alexandra, EdmontonRoyal Alexandra, Edmonton W. Hui W. Hui 6 6 Concord, SydneyConcord, Sydney D. Brieger D. Brieger 4 4 Box Hill, MelbourneBox Hill, Melbourne G. New G. New 3 3 Prince of Wales, SydneyPrince of Wales, Sydney N. Jepson N. Jepson 2 2 CHUM, MontrealCHUM, Montreal F. Reeves F. Reeves 2 2 John Hunter, NewcastleJohn Hunter, Newcastle S. Thambar S. Thambar 1 1

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Native Vessel Coronary Artery

Disease

Vein GraftDisease

Stable Angina

ST Elevation MI

Non-ST Elevation

Acute Coronary Syndromes

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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

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FilterWire EZ 3.5-5.5mm & 2.25-3.5mm

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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

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Lesion 2 Lesion 3Lesion 4 or more

TIMI 0-1 flow TIMI 2-3 flow Yes No

Cross with wire ± predilate

TIMI 2-3 flow Landing zone adequate

No Yes

Treat as per randomization*

Treat as necessary,

staged > 14 days later

Exclude

FilterWire EZ Control

Position FilterWire

Lesion 2,* Lesion 2*

Lesion 3 PCI / Stent PCI / Stent Lesion 3

Retrieve FilterWire

Angiography Angiography

Randomize

Angiography Shows Coronary Disease Suitable for PCI

Requires PCI at time of index procedure?

Decide re use of GP IIb/IIIa inhibitors

Fulfils angiographic inclusion criteria Suitable for PCI with FilterWire?

Lesion / angiographic culprit

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Primary Endpoint

In-hospital MACEIn-hospital MACE

- death, recurrent myocardial - death, recurrent myocardial infarction (CK-MB>3x normal), infarction (CK-MB>3x normal), emergency CABG, repeat target emergency CABG, repeat target vessel revascularisationvessel revascularisation

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Secondary Endpoints

MACE at 30 daysMACE at 30 days Change in CK-MB 6-24hours post-PCIChange in CK-MB 6-24hours post-PCI Change in troponin T 6-24 hours post-PCIChange in troponin T 6-24 hours post-PCI Device success – FilterWire EZDevice success – FilterWire EZ Incidence of embolic recoveryIncidence of embolic recovery TIMI flow post-PCITIMI flow post-PCI

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Baseline Characteristics

FilterWire EZ ControlFilterWire EZ Control

Patients, nPatients, n 77 77 7474Age, mean (sd)Age, mean (sd) 58(11) 58(11) 60(13)60(13)Male, %Male, % 83 83 8989European, %European, % 88 88 8888Previous angina, %Previous angina, % 40 40 4242Diabetes, %Diabetes, % 16 16 2626Smoker – never, %Smoker – never, % 29 29 3434Hypertension, %Hypertension, % 39 39 4646Dyslipidemia, %Dyslipidemia, % 69 69 6262

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Baseline Angiographic Findings

FilterWire EZ ControlFilterWire EZ Control

Reference vessel, mmReference vessel, mm 3.1(0.6)3.1(0.6)3.1(0.6)3.1(0.6)

Diameter stenosis, %Diameter stenosis, % 78(14)78(14) 76(12)76(12)Lesion location - RCA,LAD,LCXLesion location - RCA,LAD,LCX ,%,% 37,39,2437,39,24 44,32,2544,32,25Lesion length, mmLesion length, mm 15.8(7.6)15.8(7.6)

16.8(10.2)16.8(10.2)Lesion ulceration, % Lesion ulceration, % 5.65.6 11.211.2Lesion calcification - mod/severe, %Lesion calcification - mod/severe, % 2929 34 34TIMI III flow, %TIMI III flow, % 6060 67 67

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Primary Endpoint

p=0.793p=0.793

11.7

9.5

0

5

10

15

Filter Wire Control

In hospitalMACE, %

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Secondary Endpoints

FilterWire EZ ControlFilterWire EZ Control

MACE 30 day, %MACE 30 day, % 12 12 11 11

Change CK-MBChange CK-MB 5.1(20) 5.1(20) 4.1(6)4.1(6)

Change troponin TChange troponin T 0.4(0.7) 0.4(0.7) 0.4(0.6)0.4(0.6)

Device success, %Device success, % 97 97 n/a n/a

Embolic recovery, %Embolic recovery, % 42 42 n/a n/a

Post-PCI TIMI III, %Post-PCI TIMI III, % 94 94 94 94

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Subset Analyses

No difference between FilterWire EZ and No difference between FilterWire EZ and control groups in:control groups in:

Patient treated with planned glycoprotein Patient treated with planned glycoprotein IIb/IIIa inhibitorsIIb/IIIa inhibitors

Diabetic patientsDiabetic patientsPatients pre-treated with clopidogrelPatients pre-treated with clopidogrelPatients with prior thrombolytic therapy Patients with prior thrombolytic therapy

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Why Was There No Benefit With FilterWire?

Wrong patho-physiology? Wrong patho-physiology? embolism occurs during PCI for nonSTEMIembolism occurs during PCI for nonSTEMI- histology, thrombectomy, MRI- histology, thrombectomy, MRI

Wrong lesions selected?Wrong lesions selected?only 42% had emboli capturedonly 42% had emboli capturedcalcified vs thrombotic lesionscalcified vs thrombotic lesions

Incomplete protection? Incomplete protection? embolism with positioning the deviceembolism with positioning the devicefilter mouth/ vessel wall appositionfilter mouth/ vessel wall appositionincomplete side branch protectionincomplete side branch protectionsmall particle embolismsmall particle embolism

Insufficient study population?Insufficient study population?- type II error- type II error

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Summary

A-F is the only randomised trial of a A-F is the only randomised trial of a vascular protection device undertaken in vascular protection device undertaken in non-STEMI acute coronary syndrome non-STEMI acute coronary syndrome patientspatients

No difference between FilterWire EZ and No difference between FilterWire EZ and control groups in in-hospital MACE or post-control groups in in-hospital MACE or post-procedure CK-MB or troponin elevationprocedure CK-MB or troponin elevation

Routine use of vascular protection devices Routine use of vascular protection devices in such patients does not appear warrantedin such patients does not appear warranted- further angiographic analysis may reveal - further angiographic analysis may reveal sub-groups at particular risk for embolismsub-groups at particular risk for embolism