New Horizons for Patients New Horizons for Patients

with ST-Elevation Myocardial with ST-Elevation Myocardial

InfarctionInfarction

Gregg W. Stone MDGregg W. Stone MD

Columbia University Medical Center Columbia University Medical Center Cardiovascular Research FoundationCardiovascular Research Foundation

Potential Conflicts of InterestPotential Conflicts of Interest

Speaker’s name: Gregg W. Stone, MDSpeaker’s name: Gregg W. Stone, MD

I have the following potential conflicts of interest to report:I have the following potential conflicts of interest to report:

ConsultingConsulting

Employment in industryEmployment in industry

Stockholder of a healthcare companyStockholder of a healthcare company

Owner of a healthcare companyOwner of a healthcare company

Grant/Research Support: The Medicines Company and Grant/Research Support: The Medicines Company and Boston ScientificBoston Scientific

I do not have any potential conflict of interestI do not have any potential conflict of interest

Major bleedingMajor bleeding (with or without (with or without blood product transfusions) blood product transfusions)

has emerged as a has emerged as a powerful powerful independent predictor of early independent predictor of early and late mortality and late mortality in pts with in pts with NSTEMI, STEMI and in those NSTEMI, STEMI and in those

undergoing PCIundergoing PCI

Major bleedingMajor bleeding (with or without (with or without blood product transfusions) blood product transfusions)

has emerged as a has emerged as a powerful powerful independent predictor of early independent predictor of early and late mortality and late mortality in pts with in pts with NSTEMI, STEMI and in those NSTEMI, STEMI and in those

undergoing PCIundergoing PCI

FACT

Ndrepepa et al. JACC 2008;51:690–7

Time from Randomization in DaysTime from Randomization in Days

Cu

mu

lati

ve %

Mo

rta

lity

Cu

mu

lati

ve %

Mo

rta

lity

With MIWith MI 5.7%5.7%

Without major bleedWithout major bleed 2.0%2.0%

Impact of Major Bleed and MI Impact of Major Bleed and MI after Elective and Urgent PCIafter Elective and Urgent PCI

1-Year Mortality (N=6,012)1-Year Mortality (N=6,012)

Without MIWithout MI 1.9%1.9%

With major bleedWith major bleed 8.8%8.8%

Stone GW. J Inv Cardiol 2004;16(suppl G):12–17.Stone GW. J Inv Cardiol 2004;16(suppl G):12–17.

VariableVariable GroupsGroups O.R.O.R. (95% CI)(95% CI) p-valuep-value

Creatinine clear.Creatinine clear. <30 mL/min<30 mL/min 7.217.21 (2.53–20.51)(2.53–20.51)

<0.0001<0.000130–60 mL/min30–60 mL/min 3.343.34 (1.92–5.78)(1.92–5.78)

60–90 mL/min60–90 mL/min 1.571.57 (0.96–2.57)(0.96–2.57)

CHFCHF YesYes 4.38 4.38 (2.83–6.78)(2.83–6.78) <0.0001<0.0001

Major BleedingMajor Bleeding YesYes 3.263.26 (1.78–5.96)(1.78–5.96) 0.00010.0001

MI @30dayMI @30day YesYes 2.772.77 (1.62–4.75)(1.62–4.75) 0.00020.0002

Urg Revasc @30dUrg Revasc @30d YesYes 2.772.77 (1.15–6.71)(1.15–6.71) .024.024

Hx anginaHx angina YesYes 2.182.18 (1.25–3.81)(1.25–3.81) 0.0060.006

Prior MIPrior MI YesYes 1.811.81 (1.09–3.03)(1.09–3.03) 0.0230.023

DiabetesDiabetes YesYes 1.641.64 (1.10–2.44)(1.10–2.44) 0.0150.015

Predictors of 1-year MortalityPredictors of 1-year Mortality after Elective and Urgent PCIafter Elective and Urgent PCI

Stone GW. J Inv Cardiol 2004;16(suppl G):12–17.Stone GW. J Inv Cardiol 2004;16(suppl G):12–17.

0.0

0.5

1.0

1.5

2.0

2.5

3.0

0 60 120 180 240 300 360

Heparin+GPllb/llla N=3008 Bivalirudin N=2994

1-year Mortality1-year MortalityAll 6,012 Patients (ITT)All 6,012 Patients (ITT)

P value = 0.16P value = 0.16

Cu

mu

lati

ve D

eat

hs

Cu

mu

lati

ve D

eat

hs

DaysDays

2.5%2.5%

1.9%1.9%

Lincoff AM et al. JAMA 2004;292:696–703Lincoff AM et al. JAMA 2004;292:696–703

Mo

rtal

ity

(%)

Days from Randomization

0 30 60 90 120 150 180 210 240 270 300 330 360 3900

5

15

30

10

25

20

1 yearEstimate

Major Bleed only (without MI) (N=551) 12.5%28.9%Both MI and Major Bleed (N=94)

3.4%No MI or Major Bleed (N=12,557)MI only (without Major Bleed) (N=611) 8.6%

Impact of MI and Major Bleeding (non-CABG) in the First 30 Days on Risk of Death Over 1 Year

Stone GW. ACC 2007

Cox model adjusted for baseline predictors, with MI and major bleeding (non-CABG) as time-updated covariates

Cox model adjusted for baseline predictors, with MI and major bleeding (non-CABG) as time-updated covariates

Influence of Major Bleeding and MI in the First 30 Days on the Risk of Death within 30

Days

Myocardial infarction 5.25 (3.72-7.43) <0.0001

Major bleeding without or before transfusion 3.04 (1.66-5.55) <0.0001

Major bleeding after transfusion 5.45 (3.54-8.38) <0.0001

HR ± 95% CI P-valueHR (95% CI)

Stone GW. ACC 2008

Of 13,819 enrolled pts, 704 (5.1%) had a MI, 644 (4.7%) had a major bleed (non CABG), and 206 (1.5%) died within 30 days

Attributabledeaths

42.0*

38.2**

*20.4% of all deaths**18.5% of all deaths

Attributable deaths = N deathsAttributable deaths = N deathsamong pts with the time updatedamong pts with the time updatedevent (attribute) X (adj. HR – 1)/adj. HRevent (attribute) X (adj. HR – 1)/adj. HR

Attributable deaths = N deathsAttributable deaths = N deathsamong pts with the time updatedamong pts with the time updatedevent (attribute) X (adj. HR – 1)/adj. HRevent (attribute) X (adj. HR – 1)/adj. HR Mehran RM et al. Submitted

Influence of Major Bleeding and MI in the First 30 Days on Risk of Death Over 1 Year

Cox model adjusted for baseline predictors, with MI and major bleeding (non-CABG) as time-updated covariates

Cox model adjusted for baseline predictors, with MI and major bleeding (non-CABG) as time-updated covariates

Of 13,819 enrolled pts, 524 (3.8%) died within 1 year

Myocardial infarction 2.51 (1.95-3.25) <0.0001

Major bleeding without or before transfusion 2.00 (1.30-3.06) <0.0001

Major bleeding after transfusion 3.93 (2.95-5.24) <0.0001

HR ± 95% CI P-valueHR (95% CI)Attributable

deaths

51.5*

66.5**

*9.8% of all deaths**12.7% of all deaths

ACUITY: Early and Late MortalityLandmark analysis

ACUITY: Early and Late MortalityLandmark analysis

0 30 60 90 120 150 180 210 240 270 300 330 360 3900

3

4

2

1

UFH/Enoxaparin + IIb/IIIaBivalirudin + IIb/IIIa

Bivalirudin alone

30 dayEstimate

P(log rank)

1.4%0.531.6%0.391.6%

—

EstimateP

(log rank)

3.1%0.542.7%0.212.3%

30d - 1 year

—

Mo

rtal

ity

(%)

Days from Randomization

Stone GW. JAMA 2007;298:2497-506

HHarmonizing armonizing OOutcomes with utcomes with RRevascularevascularizizatiationon and and SStents in AMItents in AMI

≥≥3400* pts with STEMI with symptom onset ≤12 hours3400* pts with STEMI with symptom onset ≤12 hours

Emergent angiography, followed by triage to…Emergent angiography, followed by triage to…

Primary PCIPrimary PCICABGCABG –– Medical RxMedical Rx––

UFH + GP IIb/IIIa inhibitorUFH + GP IIb/IIIa inhibitor(abciximab or eptifibatide)(abciximab or eptifibatide)

Bivalirudin monotherapyBivalirudin monotherapy(± provisional GP IIb/IIIa)(± provisional GP IIb/IIIa)

Aspirin, thienopyridineAspirin, thienopyridine R 1:1

3000 pts eligible for stent randomization3000 pts eligible for stent randomization R 1:3

Bare metal stentBare metal stent TAXUS paclitaxel-eluting stentTAXUS paclitaxel-eluting stent

*To rand 3000 stent pts*To rand 3000 stent pts

Clinical FU at 30 days, 6 months,1 year, and then yearly through 5 years

Clinical FU at 30 days, 6 months,1 year, and then yearly through 5 years

HHarmonizing armonizing OOutcomes with utcomes with RRevascularevascularizizatiationon and and SStents in AMItents in AMI

UFH +GP IIb/IIIaN=1802

BivalirudinMonotherapy

N=1800

R 1:1

RandomizedRandomized

30 day FU*30 day FU*

* Range ±7 days* Range ±7 days

ITT populationITT population

N=1778(98.7%)

N=1777(98.7%)

N=1802 N=1800

• • • • • • Withdrew • • •Withdrew • • •

• • • • • • Lost to FU • • •Lost to FU • • •99

15151010

1313

3602 pts with STEMI3602 pts with STEMI

Stone GW et al. In press.Stone GW et al. In press.

Diff = Diff = 0.0% [-1.6, 1.5] RR = 0.99RR = 0.99 [0.76, 1.30]

PPsupsup = 0.95 = 0.95

Primary Outcome Measures (ITT)

Diff = Diff = -3.3% [-5.0, -1.6] RR = RR = 0.60 [0.46, 0.77]

PPNINI ≤ 0.0001 ≤ 0.0001

PPsupsup ≤ 0.0001 ≤ 0.0001

Diff = Diff = -2.9% [-4.9, -0.8]RR = RR = 0.76 [0.63, 0.92]

PPNINI ≤ 0.0001 ≤ 0.0001

PPsupsup = 0.005 = 0.005

1 endpoint 1 endpoint

*Not related to CABG*Not related to CABG**MACE = All cause death, reinfarction, ischemic TVR or stroke**MACE = All cause death, reinfarction, ischemic TVR or stroke

30 Day Bleeding Endpoints*30 Day Bleeding Endpoints*UFH + GP IIb/IIIaUFH + GP IIb/IIIa

(N=1802)(N=1802)BivalirudinBivalirudin(N=1800)(N=1800) P ValueP Value

Protocol Major, non CABG**Protocol Major, non CABG** 8.3%8.3% 4.9%4.9% <0.0001<0.0001

Protocol Major, AllProtocol Major, All 10.8%10.8% 6.8%6.8% <0.0001<0.0001

Protocol MinorProtocol Minor 15.4%15.4% 8.6%8.6% <0.0001<0.0001

Blood transfusionBlood transfusion 3.5%3.5% 2.1%2.1% 0.0090.009

TIMI MajorTIMI Major 5.0%5.0% 3.1%3.1% 0.0020.002

TIMI MinorTIMI Minor 4.6%4.6% 2.8%2.8% 0.0060.006

TIMI Major or MinorTIMI Major or Minor 9.6%9.6% 5.9%5.9% <0.0001<0.0001

GUSTO LT*** or SevereGUSTO LT*** or Severe 0.6%0.6% 0.4%0.4% 0.490.49

GUSTO ModerateGUSTO Moderate 5.0%5.0% 3.1%3.1% 0.0020.002

GUSTO LT or Sev or ModGUSTO LT or Sev or Mod 5.6%5.6% 3.5%3.5% 0.0020.002

*CEC adjudicated, except protocol minor; *CEC adjudicated, except protocol minor; **Primary endpoint; ***Life threatening**Primary endpoint; ***Life threatening

Thrombocytopenia

P = 0.02P = 0.02

P = 0.04P = 0.04

P = 0.002P = 0.002

<100,000 cells/mm3 <20,000 cells/mm3<50,000 cells/mm3

Stone GW et al. In press.Stone GW et al. In press.

30 Day MACE Components*30 Day MACE Components*

UFH + GP IIb/IIIaUFH + GP IIb/IIIa(N=1802)(N=1802)

BivalirudinBivalirudin(N=1800)(N=1800) P ValueP Value

DeathDeath 3.1%3.1% 2.1%2.1% 0.0470.047

- Cardiac- Cardiac 2.9%2.9% 1.8%1.8% 0.0280.028

- Non cardiac- Non cardiac 0.2%0.2% 0.3%0.3% 0.750.75

ReinfarctionReinfarction 1.8%1.8% 1.8%1.8% 0.900.90

- Q-wave- Q-wave 1.2%1.2% 1.4%1.4% 0.660.66

- Non Q-wave- Non Q-wave 0.7%0.7% 0.4%0.4% 0.370.37

Ischemic TVRIschemic TVR 1.9%1.9% 2.6%2.6% 0.180.18

- Ischemic TLR- Ischemic TLR 1.8%1.8% 2.5%2.5% 0.130.13

- Ischemic remote TVR- Ischemic remote TVR 0.3%0.3% 0.3%0.3% 1.01.0

StrokeStroke 0.6%0.6% 0.7%0.7% 0.680.68

*CEC adjudicated*CEC adjudicatedStone GW et al. In press.Stone GW et al. In press.

30 Day Mortality30 Day Mortality

Number at riskNumber at risk

BivalirudinBivalirudin 1800 1800 17581758 17511751 17461746 17421742 17291729 16661666

Heparin + GPIIb/IIIaHeparin + GPIIb/IIIa 1802 1802 17641764 17481748 17361736 17281728 17071707 16301630

Dea

th (

%)

Dea

th (

%)

Time in DaysTime in Days

3.1%

2.1%

HR [95%CI] =0.66 [0.44, 1.00]

P=0.048

Heparin + GPIIb/IIIa inhibitor (n=1802)Bivalirudin monotherapy (n=1800)

Stone GW et al. In press.Stone GW et al. In press.

30 Day Mortality: 30 Day Mortality: Cardiac and Non CardiacCardiac and Non Cardiac

Number at riskNumber at risk

BivalirudinBivalirudin 1800 1800 17581758 17511751 17461746 17421742 17291729 16661666

Heparin + GPIIb/IIIaHeparin + GPIIb/IIIa 1802 1802 17641764 17481748 17361736 17281728 17071707 16301630

Dea

th (

%)

Dea

th (

%)

Time in DaysTime in Days

2.9%

1.8%

Heparin + GPIIb/IIIa inhibitor (n=1802)Bivalirudin monotherapy (n=1800)

0.3%0.2%

Cardiac

Non cardiac

HR [95%CI] =0.62 [0.40, 0.96]

P=0.029

Stone GW et al. In press.Stone GW et al. In press.

30 Day Stent Thrombosis (N=3,124)30 Day Stent Thrombosis (N=3,124)

UFH + UFH + GP IIb/IIIaGP IIb/IIIa(N=1553)(N=1553)

BivalirudinBivalirudin(N=1571)(N=1571)

PPValueValue

ARC 30d definite or probable stent thrombosis* 1.9%1.9% 2.5%2.5% 0.300.30

- definite 1.4%1.4% 2.2%2.2% 0.090.09

- probable 0.5%0.5% 0.3%0.3% 0.240.24

- acute (≤24 hrs) 0.3%0.3% 1.3%1.3% 0.00070.0007

- subacute (>24 hrs – 30d) 1.7%1.7% 1.2%1.2% 0.280.28

*Protocol definition of stent thrombosis, CEC adjudicated*Protocol definition of stent thrombosis, CEC adjudicated

Number at riskNumber at risk

Bivalirudin Bivalirudin 16781678 16471647 16401640 16351635 16321632 16201620 1563 1563

Heparin + GPIIb/IIIa Heparin + GPIIb/IIIa 16621662 16311631 16151615 16041604 15981598 15831583 1512 1512

Dea

th (

%)

Dea

th (

%)

Time in daysTime in days

1.8%

Heparin + GPIIb/IIIa inhibitor (n=1662)Bivalirudin monotherapy (n=1678)

0.2%0.1%

Cardiac

Non cardiac

30 Day Mortality: 30 Day Mortality: PCI CohortPCI Cohort

0

1

2

3

4

5

0 5 10 15 20 25 30

2.8%

HR [95%CI] =0.63 [0.40, 0.99]

P=0.049

Stone GW et al. In press.Stone GW et al. In press.

Predictors of 30 Day MortalityPredictors of 30 Day Mortality32 Candidate Baseline Variables*32 Candidate Baseline Variables*

Demographic:Demographic: Age; sex; race; US vs. OUS; HTN, hyperlipidemia, Age; sex; race; US vs. OUS; HTN, hyperlipidemia, smoking, diabetes, diabetes on insulin, MI, PCI, CABG, CAD, smoking, diabetes, diabetes on insulin, MI, PCI, CABG, CAD, angina, CHF, major cardiac rhythm/rate disturbances, PVDangina, CHF, major cardiac rhythm/rate disturbances, PVD

Medication use at home previous 5 days:Medication use at home previous 5 days: aspirin, beta blocker, aspirin, beta blocker, thienopyridines, calcium channel blocker, ACE/ARB, diureticthienopyridines, calcium channel blocker, ACE/ARB, diuretic

Time from symptom onset to hospital ERTime from symptom onset to hospital ER

Physical exam:Physical exam: BMI; KILLIP classBMI; KILLIP class

Baseline labsBaseline labs: : Estimated CrCl, anemia, platelet count Estimated CrCl, anemia, platelet count

Medications in hospital prior to angiography:Medications in hospital prior to angiography: Randomized Randomized treatment (bivalirudin vs. heparin + GPI; pre-procedure heparin; treatment (bivalirudin vs. heparin + GPI; pre-procedure heparin; clopidogrel loadclopidogrel load

* Angiographic variables not yet available;* Angiographic variables not yet available; - treatment related variables not used- treatment related variables not used

Time-updated covariate adjusted Cox model relating Time-updated covariate adjusted Cox model relating single 30-day adverse events to 30-day mortalitysingle 30-day adverse events to 30-day mortality

Ischemic EventsIschemic Events HR (95% CI)HR (95% CI) PP deaths* deaths* C-statC-stat

ReinfarctionReinfarction 11.09 [5.44,22.59] <0.001<0.001 9.1 [8.2,9.6] 0.830.83

Ischemic TVRIschemic TVR 6.91 [3.36,14.18] <0.001<0.001 7.7 [6.3,8.4] 0.830.83

Stent thrombosis, definite**Stent thrombosis, definite**

- any- any 10.71 [3.93,29.18] <0.001<0.001 4.5 [3.7,4.8] 0.830.83

- acute (<24 hours)- acute (<24 hours) 5.88 [0.78,44.30] 0.090.09 0.8 [-0.3,1] 0.820.82

StrokeStroke 5.44 [1.67,17.69] 0.0050.005 2.4 [1.2,2.8] 0.820.82

AttributableAttributable

* Of 93 total deaths; ** in 3,124 successfully stented pts* Of 93 total deaths; ** in 3,124 successfully stented pts***Only 2 pts with acute stent thrombosis died within 30 ***Only 2 pts with acute stent thrombosis died within 30 days, 1 in each randomized groupdays, 1 in each randomized group

Time-updated covariate adjusted Cox model relating Time-updated covariate adjusted Cox model relating single 30-day adverse events to 30-day mortalitysingle 30-day adverse events to 30-day mortality

Bleeding EventsBleeding Events HR (95% CI)HR (95% CI) PP deaths* deaths* C-statC-stat

Major bleed Major bleed (non-CABG)(non-CABG) 4.43 [2.67, 7.33] <0.001<0.001 20.1 [16.3,22.5] 0.850.85

Major bleed (all)Major bleed (all) 5.92 [3.73, 9.41] <0.001<0.001 29.1 [25.6,31.3] 0.860.86

TransfusionTransfusion 3.88 [2.09, 7.20] <0.001<0.001 11.9 [8.4,13.8] 0.830.83

Thrombocytopenia**Thrombocytopenia**

- <100,000 cells/mm- <100,000 cells/mm33 3.89 [2.22, 6.84] <0.001<0.001 11.1 [8.2,12.8] 0.780.78

- <50,000 cells/mm- <50,000 cells/mm33 6.44 [2.93,14.18] <0.001<0.001 5.9 [4.6,6.5] 0.780.78

- <20,000 cells/mm- <20,000 cells/mm33 4.98 [1.20,20.66] 0.030.03 1.6 [0.3,1.9] 0.770.77

AttributableAttributable

* Of 93 total deaths; ** * Of 93 total deaths; ** 88 deaths in 3550 patientsAttributable deaths = N deaths among pts with the time Attributable deaths = N deaths among pts with the time updated event (attribute) X (adj. HR – 1)/adj. HRupdated event (attribute) X (adj. HR – 1)/adj. HR

HR [95% CI] P-valueRisk Factor

Time-updated covariate adjusted Cox model Time-updated covariate adjusted Cox model relating 30-day events to 30-day mortalityrelating 30-day events to 30-day mortality

- Complete model with MACE components and major bleeding -- Complete model with MACE components and major bleeding -

Hazard Ratio [95% CI]Hazard Ratio [95% CI]

0.01 0.1 1 10 100

C-statistic = 0.87. C-statistic = 0.87.

Reinfarction 9.75[2.72,34.91]

<0.001

Major bleeding (non CABG) 4.66[2.84, 7.63]

<0.001

Ischemic TVR 1.11[0.29, 4.21]

0.88

Stroke 2.64[0.71, 9.75]

0.15

HR [95% CI] P-valueAttributable

DeathsRisk Factor

Time-updated covariate adjusted Cox model Time-updated covariate adjusted Cox model relating 30-day events to 30-day mortalityrelating 30-day events to 30-day mortality

- - CompleteComplete model with MACE components and major bleeding - model with MACE components and major bleeding -

Hazard Ratio [95% CI]Hazard Ratio [95% CI]

0.01 0.1 1 10 100

C-statistic = 0.87. C-statistic = 0.87. Attributable deaths = N deaths among pts Attributable deaths = N deaths among pts with the time updated event (attribute) X (adj. HR – 1)/adj. HRwith the time updated event (attribute) X (adj. HR – 1)/adj. HR

*9.7% of 93 total deaths*9.7% of 93 total deaths**21.9% of 93 total deaths**21.9% of 93 total deaths

Major bleeding(Non CABG)Incidence 238 (6.8%)26 deaths with event

4.66[2.84, 7.63]

<0.001 20.4**[16.8, 22.6]

ReinfarctionIncidence 69 (2.2%)10 deaths with event

9.75[2.72,34.91]

<0.001 9.0*[6.3, 9.7]

HR [95% CI] P-valueAttributable

DeathsRisk Factor

Time-updated covariate adjusted Cox model Time-updated covariate adjusted Cox model relating 30-day events to 30-day mortalityrelating 30-day events to 30-day mortality

- - CompleteComplete model in 3,124 pts with successfully implanted stents - model in 3,124 pts with successfully implanted stents -

Hazard Ratio [95% CI]Hazard Ratio [95% CI]

0.01 0.1 1 10 100

C-statistic = 0.87. C-statistic = 0.87. Attributable deaths = N deaths among pts Attributable deaths = N deaths among pts with the time updated event (attribute) X (adj. HR – 1)/adj. HRwith the time updated event (attribute) X (adj. HR – 1)/adj. HR

*8.3% of 54 total deaths*8.3% of 54 total deaths**28.0% of 54 total deaths**28.0% of 54 total deaths

Major bleeding(non CABG)Incidence 195 (6.2%)18 deaths with event

6.22[3.33, 11.60]

<0.001 15.1** 15.1** [12.6, 16.4][12.6, 16.4]

Stent thrombosis(definite)Incidence 57 (1.8%)5 deaths with event

10.62[3.96, 28.48]

<0.001 4.5* 4.5*

[3.7, 4.8][3.7, 4.8]

1. 1. Major bleeding is a powerful independent determinant Major bleeding is a powerful independent determinant of mortality in ACS, STEMI, and in pts undergoing PCI, of mortality in ACS, STEMI, and in pts undergoing PCI, at least as important as MI/reinfarction.at least as important as MI/reinfarction.

1. 1. Major bleeding is a powerful independent determinant Major bleeding is a powerful independent determinant of mortality in ACS, STEMI, and in pts undergoing PCI, of mortality in ACS, STEMI, and in pts undergoing PCI, at least as important as MI/reinfarction.at least as important as MI/reinfarction.

Conclusions

2. In high risk pts with STEMI undergoing primary PCI, treatment with bivalirudin compared to heparin + GPI results in a significant reduction in bleeding, thrombocytopenia and transfusions, with similar rates of reinfarction, stent thrombosis, iTVR and stroke.

3. This favorable balance of adverse events results in lower 30-day mortality in primary PCI pts treated with bivalirudin rather than heparin + GPI, representing a new standard of care for pts with STEMI.