PROTECT IIPROTECT II

William O’Neill, Neal Kleiman, Jose Henriques, Simon Dixon, Joseph William O’Neill, Neal Kleiman, Jose Henriques, Simon Dixon, Joseph Massaro, Ioana Ghiu, Brijeshwar Maini, Suresh Mulukutla, Vladimir Dzavik, Massaro, Ioana Ghiu, Brijeshwar Maini, Suresh Mulukutla, Vladimir Dzavik,

James Revenaugh, Hadley Wilson, Karim Benali, Magnus OhmanJames Revenaugh, Hadley Wilson, Karim Benali, Magnus Ohman

On behalf of all PROTECT II InvestigatorsOn behalf of all PROTECT II Investigators

1

Prospective Multicenter Randomized Trial Comparing IMPELLA to IABP in High Risk PCI:

90 Day Results

20112011

2

Background

•Patients with depressed LV function and complex anatomy have limited Patients with depressed LV function and complex anatomy have limited

treatment options with the majority not eligible for CABGtreatment options with the majority not eligible for CABG

•Prophylactic IABP hemodynamic support is used for ~28,000 high risk Prophylactic IABP hemodynamic support is used for ~28,000 high risk

PCI patients annually in the USPCI patients annually in the US11

•Impella provides superior hemodynamic support compared to IABPImpella provides superior hemodynamic support compared to IABP2,32,3

•PROTECT II is the first FDA approved, prospective, multicenter study PROTECT II is the first FDA approved, prospective, multicenter study

for patients requiring hemodynamic support during for patients requiring hemodynamic support during high risk PCI high risk PCI

comparing outcomes between IABP and Impella 2.5comparing outcomes between IABP and Impella 2.5

22Maini et al, USpella registry TCT 2010. 33Seyfarth et al. JACC 2008;52(19):1584-81 1 Health Research International 2009 report: - #0514-1-US-1209-204.

3

Trial Hypothesis & Assumption

Hypothesis: Hypothesis: That the Impella system is superior to That the Impella system is superior to Intra-aortic balloon pump (IABP) in Intra-aortic balloon pump (IABP) in preventing intra- and post-procedural preventing intra- and post-procedural major adverse events. major adverse events.

ClinicalTrials.gov identifier: NCT00562016

Assumption: Assumption: 20% Major Adverse Events (MAE) rate for 20% Major Adverse Events (MAE) rate for Impella vs. 30% for IABP, Power=80%, Impella vs. 30% for IABP, Power=80%, alpha=5%, N=654 patients.alpha=5%, N=654 patients.

PROTECT II Trial Design

IMPELLA 2.5 +PCI

IABP + PCI

Primary Endpoint = 30-day Composite MAE* rate

1:1RR

4

Patients Requiring Prophylactic Hemodynamic Support During Non-Emergent High Risk PCI on

Unprotected LM/Last Patent Conduit and LVEF≤35% OR 3 Vessel Disease and LVEF≤30%

Follow-up of the Composite MAE* rate at 90 days *Major Adverse Events (MAE) : *Major Adverse Events (MAE) : Death, Stroke/TIA, Death, Stroke/TIA, MI (>3xULN CK-MB or Troponin) , MI (>3xULN CK-MB or Troponin) , Repeat Revasc, Cardiac or Vascular Operation of Vasc. Operation for Repeat Revasc, Cardiac or Vascular Operation of Vasc. Operation for limb ischemia, Acute Renal Dysfunction, Increase in Aortic insufficiency, Severe Hypotension, CPR/VT, Angio Failurelimb ischemia, Acute Renal Dysfunction, Increase in Aortic insufficiency, Severe Hypotension, CPR/VT, Angio Failure

112INVESTIGATOR SITES OPENEDPrincipal Investigators and Clinical

Research Coordinators

USA, Canada, Europe

DATA SAFETY MONITORING BOARD

(DSMB)

DATA MANAGEMENT,

DATA MONITORING,

EVENTS ADJUDICATION,

STATISTICAL ANALYSES

Harvard Clinical Research Institute

ANGIO CORELABHarvard Beth Israel

Deaconess

PROTECT II Committees & Partners

ECHO CORELABDuke Clinical Research

Institute

SPONSORABIOMED, Inc.

CLINICAL EVENTS COMMITTEE

(CEC)

5

Regional Leaders:Brij Maini (North-East, USA)

Hadley Wilson (South-East, USA)Suresh Mulukutla (East, USA)Simon Dixon (Central, USA)Neal Kleiman (Plains, USA)Jim Revenaugh (West, USA)

Vlad Dzavik (Canada)Jose Henriques (Europe)

EXECUTIVE COMMITTEEWilliam O’Neill (Chair),

Magnus Ohman, Neal Kleiman, Simon Dixon, Jose Henriques

Intermountain Med Ctr

Emory University

Univ. of Miami

Univ. of Washington

William Beaumont

Scripps Clinic

New York City:Columbia University

Mt. SinaiWeill Cornell

UPMC AGH

Boston, MA:Boston Medical Ctr

Brigham & Women’sMass General Hosp

St. Elizabeth’s

Toronto General

PROTECT II Sites That Enrolled

Texas Heart Institute

York

UAB

Southwest Methodist

Moffitt Heart

King’s Daughters

Indiana Univ.

Lankenau

Providence Hospital

Northern Michigan Strong Memorial

Oakwood

St. Louis Univ.

Univ of Chicago

Liberty Hospital

Carolina Med Ctr

Clear Lake Regional

Lourdes Hospital

Univ. of Texas

Owensboro

St. Vincent’s

Robert Packer

Methodist DeBakey

Texsan

Univ. of Kansas

Hartford HospitalSutter Memorial

Good Samaritan

Univ. of OK

Winthrop Univ. Morristown

Washington Adventist

Centennial

Aurora St. Luke’s

Integris Baptist

Geisinger Ruby Memorial

Mercy Gilbert

Henry Ford

Univ of Maryland

St. Joseph’s

Med College of GA

Univ. of Cincinnati

USC

Loyola

Munroe Regional

VA Dallas

Banner Good Sam

Alvarado Hospital

Bryan LGH

Duke

Calif. Cardiovascular

Ottawa Heart

Royal Alexandra

Riverside

Univ. of Alberta

72 Sites Enrolled72 Sites Enrolled67 USA, 4 Canada, 1 Netherlands67 USA, 4 Canada, 1 Netherlands

AMCAmsterdam

Forsyth

6

PROTECT II Enrollment & Milestones7

20082008 2010201020092009 20112011

Pa

tie

nts

En

rolle

dP

ati

en

ts E

nro

lled

*PROTECT II DSMB Stopping rule for futility = C*PROTECT II DSMB Stopping rule for futility = Conditional power at interim analysis <40%. All major adverse events were adjudicated. Database not locked yet at the time of ACC’2011All major adverse events were adjudicated. Database not locked yet at the time of ACC’2011

Goal: 654 ptsGoal: 654 pts

Interim analysisInterim analysis

Final analysisFinal analysis

PROTECT II Study Flow 8

Per Protocol population= Patients that met all inclusion and exclusion criteria.Per Protocol population= Patients that met all inclusion and exclusion criteria.Per Protocol population was pre-specified and patients were identified prospectively prior to the statistical analysis. Per Protocol population was pre-specified and patients were identified prospectively prior to the statistical analysis.

IMPELLAIMPELLA30day N= 21530day N= 215

90day F/U, N=21390day F/U, N=213

IABPIABP30day N= 21130day N= 211

90day F/U, N=21090day F/U, N=210

Per Protocol (PP) population(N=426)

Intent-To-Treat (ITT) population (N=447)

IMPELLAIMPELLAN= 224N= 224

90day F/U, N=22290day F/U, N=222

IABPIABPN= 223N= 223

90day F/U, N=22090day F/U, N=220

RandomizedRandomizedIntent-to-TreatIntent-to-Treat

N=447N=447

Not Eligible: N=635Not Eligible: N=635 47.8% Met Exclusion criteria47.8% Met Exclusion criteria 30% Patient refusal, MD decision30% Patient refusal, MD decision 13% Unknown13% Unknown 9.2% Referred for CABG9.2% Referred for CABG

(N=12)(N=12) (N=9)(N=9)

1 withdrew consent post PCI (alive)1 withdrew consent post PCI (alive)1 EF >=35%1 EF >=35%1 Not 3VD or ULM1 Not 3VD or ULM3 Active MI3 Active MI1 Severe PVD1 Severe PVD1 Platelets<700001 Platelets<700001 Creatinine>41 Creatinine>4

2 withdrew consent post PCI (alive) 2 withdrew consent post PCI (alive) 3 EF >=35%3 EF >=35%3 Not 3VD or ULM3 Not 3VD or ULM1 Active MI1 Active MI2 Severe PVD or AS2 Severe PVD or AS1 Platelets<700001 Platelets<70000

Assessed for EligibilityAssessed for EligibilityN=1082N=1082

Baseline CharacteristicsPatient CharacteristicsPatient Characteristics IABPIABP

((N=223))ImpellaImpella

((N=224))p-valuep-value

Age 67±11 68±11 0.4

Gender-Male 81.2% 79.5% 0.651

History of CHF 83.4% 91.1% 0.015

Current NYHA (Class III / IV) 54.8% 58.1% 0.5Diabetes Mellitus 50.7% 52.2% 0.7

Implantable Cardiac Defib. 31.1% 34.8% 0.4

Prior CABG 28.7% 38.4% 0.03

LVEF 24.1±6.3 23.5±6.3 0.3

STS Mortality score 6±7 6±6 0.8

Not Surgical Candidate 64.1% 63.4% 0.9

Syntax score pre-PCI 29±13 30±14 0.5

9

Hemodynamic Support Effectiveness Hemodynamic Support Effectiveness

CPO= Cardiac Power Output = Cardiac Output x Mean Arterial Pressure x 0.0022 (Fincke R, Hochman J et al CPO= Cardiac Power Output = Cardiac Output x Mean Arterial Pressure x 0.0022 (Fincke R, Hochman J et al JACC 2004; 44:340-348)

10

Cardiac Power OutputCardiac Power Output(Secondary Endpoint)(Secondary Endpoint)

Maximal Decrease in CPO on device Support from Maximal Decrease in CPO on device Support from Baseline (in x0.01 Watts)Baseline (in x0.01 Watts)

IABPIABP ImpellaImpella

N=138N=138 N=141N=141

- 4.2 ± 24- 4.2 ± 24

- 14.2 ± 27- 14.2 ± 27

p=0.001p=0.001

CPO data available only for 279 patients (N=138 IABP and N=141 Impella) CPO data available only for 279 patients (N=138 IABP and N=141 Impella)

Procedural DifferencesProcedural Differences

Procedural CharacteristicsProcedural Characteristics IABPIABP(N=223)(N=223)

ImpellaImpella(N=224)(N=224)

p-valuep-value

Use of Heparin 82.4% 93.5% <0.001IIb/IIIa Inhibitors 26.1% 13.5% 0.001Total Contrast Media (cc) 241±114 267±142 0.037Rotational Atherectomy (RA) 9.5% 14.9% 0.088

Median # of RA Passes/lesion (IQ range) 1 (1-2) 3 (2-5) 0.001 Median # of RA passes/pt (IQ range) 2.0 (2.0-4.0) 5.0 (3.5-8.5) 0.004 Median RA time/lesion (IQ range sec) 40 (20-47) 60 (40-97) 0.005 RA of Left Main Artery 3.1% 8.0% 0.024% of SVG Treatment or RA use 17.5% 25.4% 0.041Total Support Time (hour) 8.2±21.1 1.9±2.7 <0.001Discharge from CathLab on device 37.7% 5.7% <0.001

11

PROTECT II MAE OutcomePROTECT II MAE Outcome12

IABPIABP

IMPELLAIMPELLA

MAE= Major Adverse Event RateMAE= Major Adverse Event Rate

Intent to Treat (N=447)Intent to Treat (N=447)

p=0.312p=0.312

N=224N=224N=223N=223

p=0.087p=0.087

N=222N=222N=220N=220

p=0.100p=0.100

N=215N=215N=211N=211

↓ 21% MAE

p=0.029p=0.029

N=213N=213N=210N=210

Per Protocol (N=426)Per Protocol (N=426)

Per Protocol= Patients that met all incl./ excl. criteria.Per Protocol= Patients that met all incl./ excl. criteria.

MAE= Major Adverse Event RateMAE= Major Adverse Event Rate

13

N=82N=82N=82N=82 N=63N=63N=63N=63 N=68N=68N=65N=65

IABPIABP

IMPELLAIMPELLA

Study Device Learning Curve EffectStudy Device Learning Curve EffectPer Protocol Population 90day OutcomePer Protocol Population 90day Outcome

(N=423)(N=423)

90 day MAE Relative Risk [95% CI]

Relative Risk [95% CI]

Groupp-value

Interactionp-value

0.79 [0.64, 0.98] 0.029

0.70 [0.55, 0.89] 0.003

1.25 [0.79, 1.98] 0.316

0.84 [0.55, 1.28] 0.4010.79 [0.62, 1.00] 0.048

1.11 [0.74, 1.66] 0.629

0.73 [0.57, 0.93] 0.009

0.89 [0.60, 1.32] 0.568

0.76 [0.59, 0.97] 0.027

Pre-Specified Sub-group AnalysisPre-Specified Sub-group Analysis (PP)(PP)14

With Atherectomy (n=52)

Without Atherectomy (n=371)

STS ≥ 10 (n=70)

STS < 10 (n=353)

1st Impella/IABP Pt per site (n=116)

After 1st Impella/IABP Pt (n=307)

ULM / Last conduit (n=100)

3VD (n=323)

Anatomy

PCI Procedure

STS Mortality Score

Roll in subject

Overall – Per Protocol (n=423)

Impella better IABP better0.00.0 0.50.5 1.01.0 1.51.5 2.02.0

0.015

0.907

0.043

0.923

Per Protocol (PP)= Patients that Per Protocol (PP)= Patients that met all incl./ excl. criteria.met all incl./ excl. criteria.

15

HRPCI w/o Atherectomy (N=371, 88%)HRPCI w/o Atherectomy (N=371, 88%)

DeathDeath

MI (>3x ULN)MI (>3x ULN)

Stroke/TIAStroke/TIA

Repeat RevascularizationRepeat Revascularization

Vascular ComplicationVascular Complication

Acute Renal DysfunctionAcute Renal Dysfunction

Severe HypotensionSevere Hypotension

CPR / VTCPR / VT

Aortic InsufficiencyAortic Insufficiency

Angio FailureAngio Failure

11.6%11.6%

14.9%14.9%

1.1%1.1%

6.6%6.6%

2.8%2.8%

7.7%7.7%

9.4%9.4%

12.7%12.7%

0.0%0.0%

4.4%4.4%

8.9%8.9%

17.4%17.4%

2.6%2.6%

10.5%10.5%

3.7%3.7%

11.6%11.6%

12.1%12.1%

10.0%10.0%

0.0%0.0%

2.1%2.1%

CompositeComposite

IMPELLAIMPELLA IABPIABP

12.5%12.5%

37.5%37.5%

3.1%3.1%

3.1%3.1%

0.0%0.0%

21.9%21.9%

18.8%18.8%

9.4%9.4%

0.0%0.0%

0.0%0.0%

10.0%10.0%

10.0%10.0%

0.0%0.0%

30.0%30.0%

5.0%5.0%

10.0%10.0%

20.0%20.0%

15.0%15.0%

0.0%0.0%

0.0%0.0%

PROTECT II 90-day Outcome (PP)PROTECT II 90-day Outcome (PP)HRPCI with Atherectomy (N=52, 12%)HRPCI with Atherectomy (N=52, 12%)

35.9%35.9% 51.1%51.1% (p=0.003)(p=0.003)

IMPELLAIMPELLA IABPIABP

68.8%68.8% 55.0%55.0% (p=0.316)(p=0.316)

(p=0.006)(p=0.006)

(p=0.03)(p=0.03)

(p=0.399)(p=0.399)

(p=0.522)(p=0.522)

(p=0.280)(p=0.280)

(p=0.181)(p=0.181)

(p=0.616)(p=0.616)

(p=0.211)(p=0.211)

(p=0.400)(p=0.400)

(p=0.411)(p=0.411)

(p=0.208)(p=0.208)

(p=0.784)(p=0.784)

(p=0.425)(p=0.425)

(p=0.202)(p=0.202)

(p=0.271)(p=0.271)

(p=0.911)(p=0.911)

(p=0.537)(p=0.537)

Per Protocol (PP)= Patients that met all incl./ excl. criteria.Per Protocol (PP)= Patients that met all incl./ excl. criteria.

PROTECT II MAE OutcomePROTECT II MAE Outcome16

Pre-specified High Risk PCI Without Atherectomy GroupPre-specified High Risk PCI Without Atherectomy Group

Per Protocol= Patients that met all incl./ excl. criteria.Per Protocol= Patients that met all incl./ excl. criteria.

↓ 30% MAE

p=0.003p=0.003

N=181N=181N=190N=190

Per Protocol (N=374)Per Protocol (N=374)

p=0.009p=0.009

N=183N=183N=191N=191

↓ 30% MAE

IMPELLAIMPELLA

IABPIABP

Log rank test, p=0.005Log rank test, p=0.005

Per Protocol (N=374)Per Protocol (N=374)

Practical Implications of Practical Implications of

PROTECT II PROTECT II

17

PROTECT II Outcome** (PP)PROTECT II Outcome** (PP)IABPIABP

IMPELLAIMPELLA

18

**Using x8ULN for biomarkers or Q-wave for Peri-procedural MI (Stone et al Circulation 2001;104:642-647) and 2xULN for Spontaneous MI (Universal MI definition)**Using x8ULN for biomarkers or Q-wave for Peri-procedural MI (Stone et al Circulation 2001;104:642-647) and 2xULN for Spontaneous MI (Universal MI definition)

p=0.037p=0.037

N=213N=213N=210N=210

p=0.038p=0.038

↓ 38% MACCE

↓ 29% MACCE

MACCE = Death/Stroke or TIA/MI/Repeat RevascularizationMACCE = Death/Stroke or TIA/MI/Repeat Revascularization

N=211N=211N=215N=215 N=213N=213N=210N=210

Post-DischargePost-DischargeMACCEMACCE

In-hospitalIn-hospitalMACCEMACCE

Total 90 daysTotal 90 daysMACCEMACCE

p=0.595p=0.595

PROTECT II MACCE**PROTECT II MACCE** 19

Per Protocol Population, N=426Per Protocol Population, N=426

Log rank test, p=0.04Log rank test, p=0.04

**Using x8ULN threshold for biomarkers or Q-wave for Peri-procedural MI (Stone et al Circulation 2001;104:642-647) and 2xULN **Using x8ULN threshold for biomarkers or Q-wave for Peri-procedural MI (Stone et al Circulation 2001;104:642-647) and 2xULN threshold for biomarkers for Spontaneous MI (Universal MI definition)threshold for biomarkers for Spontaneous MI (Universal MI definition)

Death, Stroke, MI,Death, Stroke, MI,Repeat revasc.Repeat revasc. IABPIABP

IMPELLAIMPELLA

20

ImpellaIABPIABP

* All Per Protocol patients with Billing claim forms and data extrapolation N=249, Device expense added back in. ** Additional patients may be added in the future to the economic report***Analysis reported by Presscott Associates, Ltd

•

•

ImpellaIABPImpella

↓12% Reduction

↓16% Reduction

21

Conclusion•The use of Impella for hemodynamic support during high risk PCI is safe.The use of Impella for hemodynamic support during high risk PCI is safe.

•The superior hemodynamic support of Impella appears to have led to The superior hemodynamic support of Impella appears to have led to significant procedural differences between the two arms.significant procedural differences between the two arms.

•Impella arm had strong trends towards superior clinical outcomes for the entire Impella arm had strong trends towards superior clinical outcomes for the entire intent-to-treat population with a significant reduction of the MAE rate in the per intent-to-treat population with a significant reduction of the MAE rate in the per protocol population at 90 day follow-up.protocol population at 90 day follow-up.

•The clinical benefit was more pronounced for patients undergoing high risk The clinical benefit was more pronounced for patients undergoing high risk PCI without atherectomy with the Impella support.PCI without atherectomy with the Impella support.

•There was a significant reduction of the MACCE rate in the per protocol There was a significant reduction of the MACCE rate in the per protocol population at 90 day follow-up when a more clinically relevant threshold of CK-population at 90 day follow-up when a more clinically relevant threshold of CK-MB release for peri-procedural MI** is considered.MB release for peri-procedural MI** is considered.

**Using x8ULN for biomarkers or Q-wave for Peri-procedural MI (Stone et al Circulation 2001;104:642-647) and 2xULN for Spontaneous MI (Universal MI definition)**Using x8ULN for biomarkers or Q-wave for Peri-procedural MI (Stone et al Circulation 2001;104:642-647) and 2xULN for Spontaneous MI (Universal MI definition)

AppendixAppendix22

PrimaryPrimary Endpoint Endpoint

• Death (all cause mortality)Death (all cause mortality)

• Myocardial infarction (> Myocardial infarction (> x3 ULN x3 ULN in CK-MB or Troponin)in CK-MB or Troponin)

• Stroke/TIAStroke/TIA

• Repeat revascularization (Any PCI/CABG post index procedure)Repeat revascularization (Any PCI/CABG post index procedure)

• Need for cardiac/vascular operation or vascular operation for limb ischemiaNeed for cardiac/vascular operation or vascular operation for limb ischemia

• Acute renal dysfunctionAcute renal dysfunction

• Increase in Aortic insufficiency by more than one gradeIncrease in Aortic insufficiency by more than one grade

• Hypotension (Hypotension ( SBP <90 mmHg for ≥ 5 min requiring pressor or IV fluid SBP <90 mmHg for ≥ 5 min requiring pressor or IV fluid) )

• CPR or Ventricular arrhythmia requiring cardioversionCPR or Ventricular arrhythmia requiring cardioversion

• Angiographic failureAngiographic failure

Combined Major Adverse EventsCombined Major Adverse Events

23

PROTECT II Top 20 Enrollers24

Site # # PtsPts LeadersLeaders LocationLocation

University of Alabama, AL 40Dr Zoghbi /Dr Misra/DrAqel

Mount-Sinai Medical Ctr, NY26

Dr Sharma /Dr Kini

University of Miami, FL 25Dr Heldman /

Dr O’Neill

Columbia University, NY 21Dr Collins /Dr Moses

Pinnacle Health Med Ctr, PA 21 Dr Maini

Banner Good Sam. Med Ctr, AZ17

Dr Pershad /Dr Byrne

Methodist DeBakey, TX 15 Dr Kleiman

VA Medical Ctr Dallas, TX 14 Dr Banerjee

Univ. of Pittsburgh Med Ctr, PA 14 Dr Mulukutla

Academic Med. Ctr, Amsterdam, NL

11 Dr Henriques

Site # # PtsPts LeadersLeaders LocationLocation

Toronto General Hospital, CAN 9 Dr Dzavik

Massachusetts General Hosp, MA9 Dr Palacios

UT Medical School at Houston, TX 9

Dr Denktas

Liberty Hosp, MO 9 Dr Kramer

University of Rochester, NY 9 Dr Ling

Intermountain Medical Ctr, UT8 Dr Revenaugh

Emory Univ. Hosp Midtown, GA 8 Dr Liberman

York Hospital, PA 8Dr Nicholson/

Dr Tolerico

Northern Michigan Hosp, MI8 Dr Cannon

Providence Hospital, MI 8 Dr David

PROTECT II MAE OutcomePROTECT II MAE Outcome25

Per Protocol Patient PopulationPer Protocol Patient Population

Per Protocol= Patients that met all incl./ excl. criteria.Per Protocol= Patients that met all incl./ excl. criteria.

↓ 30% MAE

p=0.003p=0.003

N=181N=181N=190N=190

Without Atherectomy (N=374)Without Atherectomy (N=374)

p=0.009p=0.009

N=183N=183N=191N=191

↓ 30% MAE

IABPIABP

IMPELLAIMPELLA

p=0.100p=0.100

N=215N=215N=211N=211

↓ 21% MAE

p=0.029p=0.029

N=213N=213N=210N=210

All Patients (N=426)All Patients (N=426)

26

* Stone et al, Circulation 2001;104:642-647;* Stone et al, Circulation 2001;104:642-647;

Differential Impact of CK-MB Ratios Differential Impact of CK-MB Ratios on Outcomeson Outcomes

27

With Peri-procedural MI Definition With Peri-procedural MI Definition = Cardiac Biomarkers>3xULN= Cardiac Biomarkers>3xULN

IMPELLAIMPELLA

IABPIABP

Log rank test, p=0.649Log rank test, p=0.649

**8xULN (or Q-wave) is used as a relevant threshold for Peri-procedural MI (Stone et al, Circulation 2001;104:642-647). **8xULN (or Q-wave) is used as a relevant threshold for Peri-procedural MI (Stone et al, Circulation 2001;104:642-647). For Spontaneous MI (i.e, MI occurring after 72hours), 2xULN were used, unchanged from PROTECT II definition.For Spontaneous MI (i.e, MI occurring after 72hours), 2xULN were used, unchanged from PROTECT II definition.

With Peri-procedural MI Definition With Peri-procedural MI Definition = Cardiac Biomarkers>8xULN**= Cardiac Biomarkers>8xULN**

IMPELLAIMPELLA

IABPIABP

Log rank test, p=0.505Log rank test, p=0.505

Differential Impact of CK-MB Level Differential Impact of CK-MB Level and MI Incidence in PROTECT IIand MI Incidence in PROTECT II