Proximal Protection during Saphenous Vein Graft Intervention using the Proxis™ Embolic Protection System The PROXIMAL Trial Laura Mauri, MD, MSc, FACC,

Proximal Protection during Saphenous Vein Proximal Protection during Saphenous Vein Graft Intervention using the Proxis™ Embolic Graft Intervention using the Proxis™ Embolic

Protection SystemProtection System

The PROXIMAL TrialThe PROXIMAL Trial

Laura Mauri, MD, MSc, FACC , David Cox, MD, FACC, James Hermiller, MD, FACC, Joseph Massaro, PhD, Joyce Wahr, MD, Sew Wah Tay, PhD, Michael Jonas,

MD, Jeffrey J. Popma, MD, FACC, Jim Pavliska, BS, Dennis Wahr, MD, FACC, Campbell Rogers, MD, FACC,

for the PROXIMAL Investigators

J Am Coll Cardiol 2007;50:1442-49

Mauri L. et. al. J Am Coll Cardiol 2007;50:1442-49

PROXIMAL: OverviewPROXIMAL: Overview

• Background: Embolic complications during stenting of degenerated saphenous vein coronary bypass grafts are reduced, but not eliminated, by distal protection.

• Objectives: To improve outcomes further, we investigated an embolic protection device placed proximal to the target lesion that could provide protection before lesion instrumentation, allow use of conventional guidewires, and permit embolic protection in anatomy unfavorable for distal devices.


PROXIMAL: BackgroundPROXIMAL: Background

Distal embolic protection using balloon occlusion or filters reduces post-procedural complications during SVG PCI

30 d

MA

CE

(%

)02468

1012141618

FIREFilterWire

9.9%

SAFER unprotected

16.5%

11.6%

FIREGuardWire

9.6%

SAFERGuardWire

PRIDETri

Active

11.2%

PRIDEFilter/GuardWire

10.1%

Explanations for residual MACE despite distal protection may include embolization during crossing, incomplete capture, and events occurring after device removal

Webb et al: JIC, 2005, 18, 1-3Webb et al: JIC, 2005, 18, 1-3

Angiographic Angiographic Eligibility Eligibility for Embolic for Embolic Protection Protection Among SVG PCI Among SVG PCI PatientsPatients

Distal (20%)

Proximal, non-ostial(18%)

Body of Vein Graft (40%)


PROXIMAL: Study DevicePROXIMAL: Study Device

Proxis Embolic Protection System (St Jude Medical, Maple Grove, MN)

Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply.


PROXIMAL: MethodsPROXIMAL: Methods

• 594 patients undergoing stenting of 639 saphenous vein grafts were prospectively randomized, using a non-inferiority design to compare two treatment strategies: Control (distal protection whenever possible) or Test (proximal protection when possible, distal when not).

• The study was designed to test whether a treatment strategy in which proximal protection was used whenever possible would be non-inferior to a strategy of distal protection only. Rejection of the null hypothesis would indicate that the proximal protection strategy would have a primary endpoint rate (30 day MACE) not exceeding that of the distal protection strategy plus a pre-specified non-inferiority margin.


30 Day MACE: Death, MI (CPK-MB ≥3x ULN), urgent CABG, or Target Vessel Revascularization

Power analysis:

• Assumed event rate for control arm = 12.7%

• Delta = 7% (55% relative delta)

• One sided α=0.05 for non-inferiority

• 560 randomized pts provides 80% power for non-inferiority 600 pts planned

PROXIMAL: Primary EndpointPROXIMAL: Primary Endpoint


PROXIMAL: Major CriteriaPROXIMAL: Major Criteria

• Inclusion:• Normal CK/CKMB• Lesion(s) in SVG is ≥50% and <100%. Up to 2 SVGs. No

limit on number of lesions• Concomitant 1-2 native vessel PCI allowed• ≥TIMI I Flow• Device landing zone RVD ≥3.0 and 5.0 mm

• Exclusion:• MI with 24 hours• Cardiac Surgery within 60 days• Lesion(s) within 5 mm of proximal anastomotic site• LVEF < 20%• More than 2 native lesions to be treated• More that 2 SVGs to be treated


PROXIMAL: Study AlgorithmPROXIMAL: Study Algorithm

FilterWire/GuardWire

Control


Proxis

Randomization

No protection

Proxis


Proxis

Test arm: Use Proxis™ systemProxis™ system whenever possible, and FW or GW when Proxis not possible (proximal lesions)

Control arm: Use FW/GW whenever possible, and no protection when FW/GW not possible (distal lesions)

SVG PCI SVG PCI 594 pts594 ptsStratified by GP IIb/IIIa useStratified by GP IIb/IIIa use



The PROXIMAL Trial


Baseline Clinical FeaturesBaseline Clinical FeaturesControl Test P value

N patients 300 294 -

Age (mean yrs) 70+ 9 69 + 10 NS

Male gender 84% 87% NS

Diabetes mellitus 44% 43% NS

Hypertension 89% 86% NS

Hyperlipidemia 91% 91% NS

Smoker 22% 20% NS

Prior MI 60% 59% NS

Class III/IV angina 75% 78% NS

LVEF (%) 48 + 12 48 + 14 NS

GP IIb/IIIa blocker use (%)

42.3 41.5 NS


Baseline Angiographic FeaturesBaseline Angiographic FeaturesControl Test P value

N patients 300 294 -

SVG distribution 0.029

- Left Anterior Descending 16.6% 23.3% NS

- Left Circumflex 45.1% 36.1% NS

Right Coronary Artery 38.3% 40.6% NS

Reference Vessel Diameter (mm) 3.22 ± 0.60 3.28 ± 0.60 NS

Minimal Lumen Diameter (mm) 1.05±0.50 1.04±0.49 NS

Diameter stenosis (%) 67.32±13.71 68.35±13.35 NS

SVG degeneration score 39.32±21.28 39.10±21.84 NS

Plaque Volume 105.4±92.5 114.1±98.1 NS


10.0

1.01.01.7

6.4

9.2

0.0

7.9

0.70.7

0

5

10

15

Death Q wave MI Non Q waveMI

TVR MACE

Inc

ide

nc

e (

%)

Control Test

Δ = -0.8 [-4.8, +3.2]P = 0.0061 for NI

Primary Endpoint (30 Day MACE): Primary Endpoint (30 Day MACE): Intention to TreatIntention to Treat


Actual Devices UsedActual Devices Used

82%

16% 2%

ProxisDistal protectionNo protection

74%

26%

Distal protectionNo protection

Test arm

Control arm

*

*81% FilterWire, 19% GuardWire



30-Day MACE Rates


30 Day MACE: “By Device” Analysis30 Day MACE: “By Device” Analysis

1.4

10.0

11.7

0.71.1 1.4

8.5

7.1

0.0

6.3

0.40.4

1.4

2.9

4.3

0

5

10

15

Death Q wave MI Non Q wave MI TVR MACE

Inc

ide

nc

e (

%)

Distal Protection Proxis No Protection

Δ = -4.6 [upper bound 95% CI -0.05]P = 0.0001 for NI

*No protection: Primarily distal lesions randomized to

Control Arm

*



Control


Proxis

Randomization

No protection

Proxis


Proxis

Secondary Analysis: Outcomes in Patients With Lesions Secondary Analysis: Outcomes in Patients With Lesions Suitable for Either Proximal or Distal ProtectionSuitable for Either Proximal or Distal Protection


30 Day MACE: Lesions Amenable to 30 Day MACE: Lesions Amenable to Either Proximal or Distal ProtectionEither Proximal or Distal Protection

ΔΔ = -3.1 [-8.2, +2.0] = -3.1 [-8.2, +2.0]P = 0.089 for superiority, P = 0.0001 for NIP = 0.089 for superiority, P = 0.0001 for NI

6.2

11.2

0

5

10

15

Inci

den

ce (

%)

Proxis Distal Protection



Periprocedural Myonecrosis by Intention-to-Treat Analysis Population



Mauri, L. et al. J Am Coll Cardiol 2007;50:1442-1449

Periprocedural Myonecrosis by Device Analysis Population



Mauri, L. et al. J Am Coll Cardiol 2007;50:1442-1449

Periprocedural Myonecrosis by Patients Eligible for Treatment With Either Device


PROXIMAL: ConclusionPROXIMAL: Conclusion

A treatment strategy that included proximal embolic protection whenever possible during treatment of SVG lesions produced outcomes similar to those seen with a strategy using only distal embolic protection.

These results support use of proximal protection in eligible lesions.

Documents

Proximal Protection during Saphenous Vein Graft Intervention using the Proxis™ Embolic Protection System The PROXIMAL Trial Laura Mauri, MD, MSc, FACC,