Jointly Sponsored by the University of Massachusetts Medical School Office of Continuing Education...

Jointly Sponsored by the University of Massachusetts Medical School Office of Continuing Education and CMEducation Resources, LLC.

Funded by an Independent Educational Grant from The Medicines Company

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This SlideCAST is a CME-certified program that must be viewed in its entirety to receive CME credit. You should view the slides in their original order, and then access the online CME test as directed at the end of the program. If program content or total number of slides are expanded, reduced, or modified in any way, the program no longer qualifies for CME.

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This SlideCAST is designed for interventional cardiologists, cardiologists, and emergency medicine physicians, and other healthcare providers caring for patients with acute cardiovascular disease.

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Supported by an independent educational grant from The Medicines Company, Inc.


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This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of The University of Massachusetts Medical School and CMEducation Resources, LLC. The University of Massachusetts Medical School is accredited by the ACCME to provide continuing medical education for physicians.

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The University of Massachusetts Medical School designates this educational activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Accreditation InformationAccreditation Information

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It is the policy of the University of Massachusetts Medical School to ensure fair balance, independence, objectivity and scientific rigor in all activities. All faculty participating in CME activities sponsored by the University of Massachusetts Medical School are required to present evidence-based data, identify and reference off-label product use and disclose all relevant financial relationships with those supporting the activity or others whose products or services are discussed. Faculty disclosure will be provided in the activity materials.

For additional CME-certified programs in cardiovascular health:

Please visit us at www.EDICTforACS.com (click anywhere on banner below)


http://www.edictforacs.com/

Deepak L. Bhatt, MD, FACC, FSCAI, FESC, FACP

Associate Director, Cleveland Clinic Cardiovascular Coordinating CenterStaff, Cardiac, Peripheral, and Carotid InterventionAssociate Professor of MedicineDepartment of Cardiovascular MedicineCleveland Clinic Foundation

Frederick Feit, MD, FACCDirectorCardiac Catheterization and Interventional

CardiologyBellevue Hospital CenterAssociate Professor of MedicineNew York University School of MedicineNew York, NY

Deborah Diercks, MDAssistant Professor of MedicineDepartment of Emergency MedicineUniversity of CaliforniaDavis, California

James Ferguson III, MDAssociate Director, Cardiology ResearchTexas Heart Institute at St. Luke's Episcopal

HospitalAssociate ProfessorBaylor College of MedicineClinical Assistant ProfessorUniversity of Texas Health Science Center at

Houston

Christopher Granger, MDAssociate Professor of MedicineDirector of Cardiac Care UnitDivision of Cardiovascular MedicineDuke University Medical Center

ACS Forum Leadership Panel

Judd E. Hollander, MDProfessorClinical Research DirectorDepartment of Emergency MedicineUniversity of PennsylvaniaPhiladelphia, PA

David M. Lang, DO, FACOEP,

FACEP ChiefEmergency MedicineMount Sinai Medical CenterMiami Beach, FL

Steven V. Manoukian, MD, FACCDirector, Interventional CardiologyEmory-Crawford Long HospitalEmory University School of MedicinePresidentAmerican Heart Association, Atlanta DivisionAtlanta, GA

Ralph G. Nader, MD, FACC, FACP, FSCAI

Co-Medical Director Cardiovascular Labs at Mount-Sinai/Miami HeartMiami, FL

E. Magnus Ohman, MD, FRCPI, FACC

Professor of MedicineDirector, Program for Advanced Coronary DiseaseDivision of CardiologyDuke University Medical CenterDurham, NC


Charles Pollack, MD, FACEPChairman, Department of Emergency

MedicinePennsylvania HospitalProfessor of Emergency MedicineUniversity of PennsylvaniaSchool of Medicine

Philadelphia, PA

Sunil V. Rao MDAssistant Professor of MedicineDuke University Medical CenterDirector, Cardiac Catheterization

LaboratoriesDurham VA Medical CenterDurham, NC


Deepak L. Bhatt, MD: Consultant/Honoraria or Grant/Research Support: Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, Eisai, Glaxo Smith Kline, Millennium, Paringenix, PDL, Schering Plough, sanofi-aventis, The Medicines Company.

Deborah Diercks, MD: Grants/Research Support: Invoice Technology, The Medicines Company. Consultant: Invoice Technology, sanofi-aventis U.S., Astellas. Speaker’s Bureau: Bristol-Myers Squibb, Schering-Plough, sanofi-aventis U.S

Frederick Feit, MD: Consultant: The Medicines Company

James Ferguson III, MD: Grant/Research Support: Eisai Pharmaceuticals, The Medicines Company. Vitatron/Medtronic. Consulting/Honoraria: Bristol Myers-Squibb, Eisai Pharmaceuticals, GlaxoSmithKline, Prism Pharmaceuticals, sanofi-aventis, Schering-Plough, Takeda, The Medicines Company, Therox. Speaker’s Bureau: Bristol Myers-Squibb, sanofi-aventis, Schering-Plough

Ralph G. Nader, MD: Nothing to disclose.

E. Magnus Ohman, MD: Research Grants: Berlex, sanofi-aventis, Schering-Plough Corporation, Bristol Meyer Squibb, Millennium. Stockholder: Medtronic. Consultant: Response Biomedical, Liposcience, Inovise Medical

ACS Leadership Panel Financial Disclosures

Christopher Granger, MD: Educational Grants and/or Research Support: Alexion, Astra Zeneca, Procter and Gamble, sanofi-aventis, Novartis, Boehringer Ingelheim, Genentech, and Berlex

Judd E. Hollander, MD: Grant/Research Support: sanofi-aventis, Biosite, Scios, The Medicines Company. Consultant: sanofi-aventis, Biosite, Scios, The Medicines Company. Speaker’s Bureau: sanofi-aventis, Biosite, Scios, The Medicines Company

David Lang, DO: Honoraria: Roche and Pfizer. Consultant: Aventis

Steven V. Manoukian, MD: Grant/ Research Support: The Medicines Company Speaker’s Bureau: The Medicines Company

Charles Pollack, MD: Grant/Research Support: GlaxoSmithKline. Consultant: The Medicines Company, Schering-Plough, sanofi-aventis, BMS, Genentech. Speaker’s Bureau: Schering-Plough, sanofi-aventis, BMS, Genentech

Sunil V. Rao, MD: Consultant: sanofi-aventis, The Medicines Company, Pfizer, Cordis. Research funding: Agency for Healthcare Research & Quality, National Institute for Aging, American College of Cardiology

ACS Leadership Panel Financial Disclosures

Thomas Amidon, MDThe Hope Heart Institute

Atul Aggarwal, MDNebraska Heart Institute

Himanshu Aggarwal, MDNebraska Heart Institute

Keith Benzuly, MD, FACCNorthwestern University

Joseph J. Brennan Jr., MDYale University School of Medicine

Carl Chudnofsky, MDAlbert Einstein Medical Center

Michael J. Cowley, MDMedical College of Virginia

Harold Dauerman, MDUniversity of Vermont

William J. French, MDUCLA Medical Center

Satyendra Giri, MDBaystate Health Systems

Paul A. Gurbel, MDJohns Hopkins University

ACS Faculty Review Committee

* Complete affiliations and financial disclosures for Review Committee members are listed at end of slide deck.

Tim Henry, MDMinneapolis Heart Institute

Kurt Kleinschmidt, MDUT Southwestern Medical Center

James Leggett, MDHope Heart Institute

Glenn Levine, MDBaylor College of Medicine

John J. Lopez, MDUniversity of Chicago

Reginald Low, MDUniversity of California, Davis

Roberto Medina, MDFlorida Medical Clinic

Barry L. Molk, MD, FACCUniversity of Colorado

Reynaldo Mulingtapang, MDUniversity of South Florida

Robert A. Mulliken, MDUniversity of Chicago Hospitals

Sandeep Nathan, MD, FACCRush Medical College

Paul E. Pepe, MD, MPHUT Southwestern Medical Center



Robert N. Piana, MDVanderbilt University

Vincent J. Pompili, MD, FACCCase School of Medicine

Matthew J. Price, MDScripps Clinic

Douglas J. Spriggs, MD, FACCUniversity of South Florida

Lowell H. Steen, Jr., MDLoyoyla University Chicago

David J. Robinson, MD, MS, FACEPUT Health Sciences Center

Joseph F. Stella, DO, FACCHeart Care Centers of Illinois

Rex J. Winters, MDLong Beach Memorial Heart Institute



►Physicians will learn about the impact that bleeding has on outcomes in patients with acute coronary ischemic syndromes (ACS)

►Physicians will learn what factors predict bleeding in patients with ACS

►Physicians will learn what predictive value different bleeding scales have on outcomes in patients with ACS

►Physicians will learn how to implement strategies that balance risk of bleeding and ischemia.

►Physicians will learn how to apply landmark trials and analyses of bleeding and ACS to clinical situations.

Educational Objectives

A Science-to-Strategy Analysis of BleedingIssues in Acute Coronary Syndromes

A Science-to-Strategy Analysis of BleedingIssues in Acute Coronary Syndromes

BLEEDING IN THE SETTING OFACUTE CORONARY SYNDROMES (ACS)

Clinical Implications and Effects on Mortality and Resource Utilization

A CME-Certified Activity Developed by the National Experts' Educational Forum in Cardiovascular Disease

BLEEDING IN THE SETTING OFACUTE CORONARY SYNDROMES (ACS)

Clinical Implications and Effects on Mortality and Resource Utilization

A CME-Certified Activity Developed by the National Experts' Educational Forum in Cardiovascular Disease

Medical Rx(cath)

Time

Admission Cath Discharge

No Cath

Cath PCI

Surgery

Medical Rx (no cath)

Medical Rx

No disease

(82 % of total)

(18 % of total)

(52% of total, 63% of those undergoing cath)

40 % < 48 hrs

12 % > 48 hrs

(12% of total, 15% of those undergoing cath)

63 % < 48 hrs

19 % > 48 hrs

CRUSADERegistry

10/04-9/05n=35,897

Patient X

ACS Management Pathways

Cath

Medical Rx

SYNERGY

LMWHLMWH

ESSENCEESSENCE

19941994 19951995 19961996 19971997 19981998 19991999 20002000 20022002 20032003 20042004 20052005 2006200620012001

CURECURE

ClopidogrelClopidogrel

Bleeding riskBleeding risk

Ischemic riskIschemic risk

GP IIb/IIIa GP IIb/IIIa blockersblockers

PRISM-PLUSPRISM-PLUS

PURSUITPURSUIT

ACUITYTACTICS TIMI-18TACTICS TIMI-18

Early invasiveEarly invasive

PCIPCI ~ 5% stents~ 5% stents ~85% stents~85% stents Drug-eluting stentsDrug-eluting stents

ISAR-REACT 2

Milestones in ACS Management

OASIS-5

[ Fondaparinux ][ Fondaparinux ]

Anti-Thrombin RxAnti-Thrombin Rx

Anti-Platelet RxAnti-Platelet Rx

Treatment StrategyTreatment Strategy

HeparinHeparin

AspirinAspirin

ConservativeConservative

ICTUS

BivalirudinBivalirudin

REPLACE 2REPLACE 2

Adapted from and with the courtesy of Steven Manoukian, MD.Adapted from and with the courtesy of Steven Manoukian, MD.Adapted from and with the courtesy of Steven Manoukian, MD.Adapted from and with the courtesy of Steven Manoukian, MD.

Ischemic Complications Ischemic

Complications

► Death

► MI

► Urgent TVR

► Death

► MI

► Urgent TVR

Evolving Paradigm for Evaluating ACS Evolving Paradigm for Evaluating ACS Management StrategiesManagement Strategies

Composite Adverse Event EndpointsComposite Adverse Event Endpoints

Ischemic Complications Ischemic

Complications Hemorrhage HIT

Hemorrhage HIT

► Death

► MI

► Urgent TVR

► Death

► MI

► Urgent TVR

► Major Bleeding

► Minor Bleeding

► Thrombocytopenia

► Major Bleeding

► Minor Bleeding

► Thrombocytopenia




Periprocedural

Complications

Periprocedural

Complications

Clinical BenefitClinical Benefit

► Death

► Major Disability

► Death

► Major Disability

► Cost

► Ease of Use

► Duration of Therapy

► Accounting for Bleeding and Ischemic Endpoints

► Cost

► Ease of Use

► Duration of Therapy

► Accounting for Bleeding and Ischemic Endpoints




Risk of events

Risk of bleeding

ThrombosisHemostasis

Two sides of the same coin

Degree of Anticoagulation

Ris

k

Balancing Events and BleedingBalancing Events and BleedingBalancing Events and BleedingBalancing Events and Bleeding

DeathDeath 4.3%4.3%

(Re)-Infarction(Re)-Infarction 2.5%2.5%

CHFCHF 8.0%8.0%

Cardiogenic ShockCardiogenic Shock 2.6%2.6%

StrokeStroke 0.8%0.8%

Non-CABG TransfusionNon-CABG Transfusion 9.9%9.9%

Bhatt DL, et al. Bhatt DL, et al. JAMAJAMA. 2004 Nov 3;292(17):2096-104. . 2004 Nov 3;292(17):2096-104.

CRUSADE In-Hospital OutcomesCRUSADE In-Hospital Outcomes

Bleeding in ACS - AgendaBleeding in ACS - Agenda

► Predictors of bleeding in ACSPredictors of bleeding in ACS

► Outcomes associated with bleedingOutcomes associated with bleeding Impact of definition on outcomesImpact of definition on outcomes

► Outcomes associated with blood Outcomes associated with blood transfusiontransfusion

► Special populations at riskSpecial populations at risk ElderlyElderly Chronic kidney diseaseChronic kidney disease AnemiaAnemia

► Cost implications of bleeding Cost implications of bleeding

What predicts bleeding among patients

with ACS ?

What predicts bleeding among patients

with ACS ?

Bleeding in ACS

Question to be answered:Question to be answered:

Independent Independent Predictors of Predictors of Major Bleeding Major Bleeding in Marker Positive in Marker Positive Acute Coronary Acute Coronary SyndromesSyndromes

Moscucci, GRACE Registry, Moscucci, GRACE Registry, Eur Heart JEur Heart J. 2003 Oct;24(20):1815-23. . 2003 Oct;24(20):1815-23.

Predictors of Major Bleeding in ACSPredictors of Major Bleeding in ACS

► Older AgeOlder Age

► Female GenderFemale Gender

► Renal FailureRenal Failure

► History of BleedingHistory of Bleeding

► Right Heart CatheterizationRight Heart Catheterization

► GPIIb-IIIa antagonistsGPIIb-IIIa antagonists

0 1 2 3

P-valueP-valueRR (95% CI)RR (95% CI)Risk ratio ± 95% CIRisk ratio ± 95% CIRisk ratio ± 95% CIRisk ratio ± 95% CI

Predictors of Major BleedingPredictors of Major Bleeding

Age Age >>75 (vs. 55-75)75 (vs. 55-75)

AnemiaAnemia

CrCl <60mL/minCrCl <60mL/min

DiabetesDiabetes

Female genderFemale gender

High-risk (ST / biomarkers)High-risk (ST / biomarkers)

HypertensionHypertension

No prior PCINo prior PCI

Prior antithrombotic therapyPrior antithrombotic therapy

Heparin(s) + GPI (vs. Bivalirudin)Heparin(s) + GPI (vs. Bivalirudin)

1.56 (1.19-2.04)1.56 (1.19-2.04) 0.00090.0009

1.89 (1.48-2.41)1.89 (1.48-2.41) <0.0001<0.0001

1.68 (1.29-2.18)1.68 (1.29-2.18) <0.0001<0.0001

1.30 (1.03-1.63)1.30 (1.03-1.63) 0.02480.0248

2.08 (1.68-2.57)2.08 (1.68-2.57) <0.0001<0.0001

1.42 (1.06-1.90)1.42 (1.06-1.90) 0.01780.0178

1.33 (1.03-1.70)1.33 (1.03-1.70) 0.02870.0287

1.47 (1.15-1.88)1.47 (1.15-1.88) 0.00190.0019

1.23 (0.98-1.55)1.23 (0.98-1.55) 0.07680.0768

2.08 (1.56-2.76)2.08 (1.56-2.76) <0.0001<0.0001

Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.

Results: The ACUITY Trial PCI PopulationResults: The ACUITY Trial PCI PopulationResults: The ACUITY Trial PCI PopulationResults: The ACUITY Trial PCI Population

0 1 2 3 4 5

P-valueP-valueRR (95% CI)RR (95% CI)

Age Age >>75 (vs. 55-75)75 (vs. 55-75)

AnemiaAnemia

CrCl <60mL/minCrCl <60mL/min

DiabetesDiabetes

Female genderFemale gender

High-risk (ST / biomarkers)High-risk (ST / biomarkers)

HypertensionHypertension

HeparinHeparin(s)(s) + GPI + GPI (vs. Bivalirudin)(vs. Bivalirudin)

1.420 (1.055-1.910)1.420 (1.055-1.910) 0.00600.0060

3.764 (2.919-4.855)3.764 (2.919-4.855) <0.0001<0.0001

2.097 (1.568-2.803)2.097 (1.568-2.803) <0.0001<0.0001

1.560 (1.209-2.014)1.560 (1.209-2.014) 0.00600.0060

2.233 (1.739-2.867)2.233 (1.739-2.867) <0.0001<0.0001

1.754 (1.297-2.372)1.754 (1.297-2.372) 0.00030.0003

1.457 (1.051-2.020)1.457 (1.051-2.020) 0.02410.0241

1.728 (1.256-2.379)1.728 (1.256-2.379) 0.00070.0007

Predictors of TransfusionPredictors of Transfusion

Risk ratio ± 95% CIRisk ratio ± 95% CIRisk ratio ± 95% CIRisk ratio ± 95% CI


Results: The ACUITY TrialResults: The ACUITY TrialResults: The ACUITY TrialResults: The ACUITY Trial

REPLACE-2REPLACE-2Multivariate Predictors of Major BleedingMultivariate Predictors of Major Bleeding

RISK FACTORSRISK FACTORS Odds RatioOdds Ratio 95% CI95% CI p-valuep-value

Baseline risk factorsBaseline risk factors

Age Age >> 75 75 1.4821.482 1.009 to 2.1761.009 to 2.176 0.0450.045

Gender (M vs. F)Gender (M vs. F) 0.6520.652 0.477 to 0.8900.477 to 0.890 0.00720.0072

Prior AnginaPrior Angina 1.5891.589 1.077 to 2.3451.077 to 2.345 0.01970.0197

Creatinine clearance* Creatinine clearance* 0.9930.993 0.987 to 0.9980.987 to 0.998 0.00610.0061

AnemiaAnemia 1.4031.403 1.015 to 1.9391.015 to 1.939 0.04010.0401

Peri-procedural risk factorsPeri-procedural risk factors

Treatment Group (BIV vs. H+GPI)Treatment Group (BIV vs. H+GPI) 0.5080.508 0.352 to 0.7330.352 to 0.733 0.00030.0003

Provisional GPI receivedProvisional GPI received 2.6792.679 1.591 to 4.5121.591 to 4.512 0.00020.0002

Procedure Duration >1hProcedure Duration >1h 2.0492.049 1.217 to 3.4491.217 to 3.449 0.00690.0069

Time to Sheath Removal >6hTime to Sheath Removal >6h 1.6141.614 1.064 to 2.4481.064 to 2.448 0.02440.0244

ICU stay (days)†ICU stay (days)† 1.251.25 1.183 to 1.3211.183 to 1.321 <0.0001<0.0001

IABPIABP 8.7058.705 3.433 to 22.0723.433 to 22.072 <0.0001<0.0001Feit F et al. Unpublished (in manuscript)

► Older age, chronic kidney disease, female gender are consistently associated with bleeding and blood transfusion

► Analysis of large randomized trials have also identified novel risk factors for bleeding such as diabetes and anemia

► Procedural characteristics such as procedure duration and sheath dwell time also predict bleeding complications

► Older age, chronic kidney disease, female gender are consistently associated with bleeding and blood transfusion

► Analysis of large randomized trials have also identified novel risk factors for bleeding such as diabetes and anemia

► Procedural characteristics such as procedure duration and sheath dwell time also predict bleeding complications

Bleeding Predictors—Conclusions

Does bleeding influence the prognosis

of ACS patients ?

Does bleeding influence the prognosis

of ACS patients ?

Bleeding in ACS


Moscucci M et al. Moscucci M et al. Eur Heart JEur Heart J 2003;24:1815-23. 2003;24:1815-23.

P<0.001

5.13.0

5.37.0

18.616.1 15.3

22.8

0.0

10.0

20.0

30.0

40.0

No Bleed

Bleed

Overall Unstable NSTEMI STEMIOverall Unstable NSTEMI STEMI ACS AnginaACS Angina

Pat

ien

ts (

%)

Pat

ien

ts (

%)

Major Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACSMajor Bleeding Predicts Mortality in ACS

24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death24,045 ACS patients in the GRACE registry, in-hospital death

log rank p-value for all four categories <0.0001log-rank p-value for no bleeding vs. mild bleeding = 0.02log-rank p-value for mild vs. moderate bleeding <0.0001log-rank p-value for moderate vs. severe <0.001

Bleeding & OutcomesBleeding & Outcomes

Rao SV, et al. Rao SV, et al. Am J CardiolAm J Cardiol. 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 . 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 Rao SV, et al. Rao SV, et al. Am J CardiolAm J Cardiol. 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 . 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12

Kaplan Meier Curves for 30-Day Death, Stratified by Bleed SeverityKaplan Meier Curves for 30-Day Death, Stratified by Bleed Severity

N=26,452 ACS patients from GUSTO IIb, PARAGON A, PARAGON B, & PURSUIT N=26,452 ACS patients from GUSTO IIb, PARAGON A, PARAGON B, & PURSUIT

26,452 patients from PURSUIT, PARAGON A, 26,452 patients from PURSUIT, PARAGON A, PARAGON B, GUSTO IIb NSTPARAGON B, GUSTO IIb NST

Bleeding severity and adjusted hazard of deathBleeding severity and adjusted hazard of death

*p<0.0001*p<0.0001

Bleeding and Outcomes in NSTE ACS Bleeding and Outcomes in NSTE ACS

Bleeding SeverityBleeding Severity 30d Death30d Death 30d Death/MI30d Death/MI 6 mo. Death6 mo. Death

Mild*Mild* 1.6 1.6 1.31.3 1.41.4

Moderate*Moderate* 2.7 2.7 3.33.3 2.12.1

Severe*Severe* 10.610.6 5.65.6 7.57.5

*Bleeding as a time-dependent covariate*Bleeding as a time-dependent covariate

Rao SV, et al. Rao SV, et al. Am J CardiolAm J Cardiol. 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 . 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 Rao SV, et al. Rao SV, et al. Am J CardiolAm J Cardiol. 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12 . 2005 Nov 1;96(9):1200-6. Epub 2005 Sep 12

9.3%

3.0%

17.1%

5.4%

24.2%

5.5%7.8%

0.8%

IschemicComposite

Death MI (all) UnplannedRevasc

30 d

ay e

ven

ts (

%)

Major Bleeding (N=462, 5.9%) No Major Bleeding (N=7327, 94.1%)

Major Bleeding, Ischemic Endpoints, Major Bleeding, Ischemic Endpoints, and Mortalityand Mortality

9.3%

3.0%

17.1%

5.4%

24.2%

5.5%7.8%

0.8%

IschemicComposite


30 d

ay e

ven

ts (

%)


P<0.0001 for all


Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)

4.8%

12.6%

17.1%

0.8%

5.5% 4.8%

MI (all) Non-Q MI Q-MI

30 d

ay e

ven

ts (

%)


Major Bleeding and Myocardial InfarctionMajor Bleeding and Myocardial Infarction

4.8%

12.6%

17.1%

0.8%

5.5% 4.8%


30 d

ay e

ven

ts (

%)


P<0.0001 for all


Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)Results: The ACUITY Trial PCI Population (N=7,789)

Major and Minor Bleeding in PCIMajor and Minor Bleeding in PCIBleeding Increases Mortality and EventsBleeding Increases Mortality and Events

Kinnaird TD et al. AM J Cardiol 2003;92:930-5.

10,974 patients undergoing PCI, Washington Hospital Center, 1991-2000.

In-Hospital Clinical EventsIn-Hospital Clinical Events

MajorMajor(n=588)(n=588)

MinorMinor(n=1,394)(n=1,394)

NoneNone(n=8,992)(n=8,992)

DeathDeath 7.5%*7.5%*†† 1.8%*1.8%* 0.6%0.6%

Q-wave myocardial infarctionQ-wave myocardial infarction 1.2%*1.2%* 0.7%0.7%‡‡ 0.2%0.2%

Non-Q-wave myocardial infarctionNon-Q-wave myocardial infarction 30.7%*30.7%*†† 16.8%*16.8%* 11.8%11.8%

Repeat lesion angioplastyRepeat lesion angioplasty 1.9%*1.9%*§§ 0.8%0.8%‡‡ 0.3%0.3%

Major adverse cardiac eventMajor adverse cardiac event 6.6%*6.6%*†† 2.2%*2.2%* 0.6%0.6%

Bleeding ComplicationBleeding Complication

* p<0.001 versus none † p<0.001 versus minor ‡ p<0.01 versus none § p<0.05 versus minor

► Bleeding is associated with adverse short- and long-term outcomes among patients with ACS and those undergoing PCI

Mortality rates are higher among those who bleed

MI rates are higher among those who bleed

► The risk is “loss-dependent” with worse bleeding associated with worse outcomes

► This relationship is persistent after robust statistical adjustment for confounders

► Bleeding is associated with adverse short- and long-term outcomes among patients with ACS and those undergoing PCI

Mortality rates are higher among those who bleed

MI rates are higher among those who bleed

► The risk is “loss-dependent” with worse bleeding associated with worse outcomes

► This relationship is persistent after robust statistical adjustment for confounders

Bleeding and Outcomes—Conclusions

How does one assess bleeding

severity?

How does one assess bleeding

severity?

Bleeding in ACS


Bleeding Incidence in ACS Clinical TrialsBleeding Incidence in ACS Clinical Trials

0.4

10

1.2

4

1.5

3.7

9.1

0

2

4

6

8

10

12

GUSTO IIb OASIS-2 PRISM-PLUS PURSUIT PRISM CURE SYNERGY

%

Rao SV, et al. J Am Coll Cardiol. 2006 Feb 21;47(4):809-16. Epub 2006 Jan 26 Rao SV, et al. J Am Coll Cardiol. 2006 Feb 21;47(4):809-16. Epub 2006 Jan 26

Bleeding DefinitionsBleeding Definitions

► TIMI DefinitionTIMI Definition MajorMajor

• ICHICH• Associated with Hgb decrease ≥ 5 g/dl or Associated with Hgb decrease ≥ 5 g/dl or

HCT decrease ≥ 15%HCT decrease ≥ 15% MinorMinor

• Observed blood loss associated with Hgb Observed blood loss associated with Hgb decrease ≥ 3 g/dl or HCT decrease ≥ 10%decrease ≥ 3 g/dl or HCT decrease ≥ 10%

• No identifiable source but Hgb decrease No identifiable source but Hgb decrease ≥ 4 g/dl or HCT decrease ≥ 12%≥ 4 g/dl or HCT decrease ≥ 12%

MinimalMinimal• Overt hemorrhage with Hgb drop < 3 g/dl or Overt hemorrhage with Hgb drop < 3 g/dl or

HCT drop < 9%HCT drop < 9%

Chesebro JH. Chesebro JH. CirculationCirculation 1987. Jul;76(1):142-54. 1987. Jul;76(1):142-54. Chesebro JH. Chesebro JH. CirculationCirculation 1987. Jul;76(1):142-54. 1987. Jul;76(1):142-54.

N Engl J MedN Engl J Med. 1993 Nov 25;329(22):1615-22. Erratum in: . 1993 Nov 25;329(22):1615-22. Erratum in: N Engl J MedN Engl J Med 1994 Feb 17;330(7):516 1994 Feb 17;330(7):516 N Engl J MedN Engl J Med. 1993 Nov 25;329(22):1615-22. Erratum in: . 1993 Nov 25;329(22):1615-22. Erratum in: N Engl J MedN Engl J Med 1994 Feb 17;330(7):516 1994 Feb 17;330(7):516

Bleeding DefinitionsBleeding Definitions

► GUSTO DefinitionGUSTO Definition Severe or life threateningSevere or life threatening

• ICH or hemodynamic compromise ICH or hemodynamic compromise requiring treatmentrequiring treatment

ModerateModerate• Requiring transfusionRequiring transfusion

MildMild• Not meeting criteria for Severe or Not meeting criteria for Severe or

ModerateModerate

Bleeding Incidence Among 15,858 NSTEBleeding Incidence Among 15,858 NSTEACS Patients: Impact of DefinitionACS Patients: Impact of Definition

8.5 8.2

12.7

1.2

11.4

19.2

0

5

10

15

20

25

GUSTOMild

GUSTOMod

GUSTO Sev TIMI Mini TIMI Min TIMI Maj

%


Bleeding Scales Among Bleeding Scales Among NSTE ACS PatientsNSTE ACS Patients


TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858TIMI and GUSTO – Adjusted Hazard of 30 d Death/MI N=15,858

► Clearly defining bleeding severity can be difficult, but there are definitions that have been used in clinical trials and registries

► Not all of these definitions have been validated in terms of prognosis

► TIMI and GUSTO are 2 of the most commonly used definitions

► Bleeding definitions that include clinical events (e.g. GUSTO) are better at predicting outcomes

► Clearly defining bleeding severity can be difficult, but there are definitions that have been used in clinical trials and registries

► Not all of these definitions have been validated in terms of prognosis

► TIMI and GUSTO are 2 of the most commonly used definitions

► Bleeding definitions that include clinical events (e.g. GUSTO) are better at predicting outcomes

Bleeding Definitions—Conclusions

► Do blood transfusions have predictive

value?

► Do blood transfusions correct negative

impact of bleeding?

► Do blood transfusions have predictive

value?

► Do blood transfusions correct negative

impact of bleeding?

Bleeding in ACS

Questions to be answered:Questions to be answered:

30-Day Survival By Transfusion Group30-Day Survival By Transfusion Group

Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562

Transfusion in ACSTransfusion in ACS

N=24,111N=24,111N=24,111N=24,111

*Transfusion as a time-dependent covariate*Transfusion as a time-dependent covariate

PRBC Transfusion Among NSTE ACS Patients:PRBC Transfusion Among NSTE ACS Patients:Cox Model for 30-day DeathCox Model for 30-day Death

Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562Rao SV, et. al., Rao SV, et. al., JAMAJAMA 2004;292:1555–1562 2004;292:1555–1562

N=24,111N=24,111N=24,111N=24,111

Adjusted Risk of In-Hospital Outcomes Adjusted Risk of In-Hospital Outcomes

By Transfusion Status*By Transfusion Status*

*Non-CABG patients onlyYang X, Yang X, J Am Coll CardiolJ Am Coll Cardiol 2005;46:1490–5. 2005;46:1490–5.Yang X, Yang X, J Am Coll CardiolJ Am Coll Cardiol 2005;46:1490–5. 2005;46:1490–5.

N=74,271 ACS patients from CRUSADEN=74,271 ACS patients from CRUSADE

9.4%

2.3%

18.8%

11.0%

29.2%

4.8%7.1%

1.3%

IschemicComposite


30 d

ay e

ven

ts (

%)

Transfusion (N=319, 2.3%) No Transfusion (N=13500, 97.7%)

Transfusion, Ischemic Endpoints, and Transfusion, Ischemic Endpoints, and MortalityMortality

9.4%

2.3%

18.8%

11.0%

29.2%

4.8%7.1%

1.3%

IschemicComposite


30 d

ay e

ven

ts (

%)


P<0.0001 for all


Results: The ACUITY Trial (N=13,819)Results: The ACUITY Trial (N=13,819)Results: The ACUITY Trial (N=13,819)Results: The ACUITY Trial (N=13,819)

5.3%

13.8%

18.8%

0.9%

4.8% 3.8%


30 d

ay e

ven

ts (

%)


Transfusion and Myocardial InfarctionTransfusion and Myocardial Infarction

5.3%

13.8%

18.8%

0.9%

4.8% 3.8%


30 d

ay e

ven

ts (

%)


P<0.0001 for all


Results: The ACUITY Trial (N=13,819)Results: The ACUITY Trial (N=13,819)Results: The ACUITY Trial (N=13,819)Results: The ACUITY Trial (N=13,819)

Increased 1-year mortality in transfused patientsIncreased 1-year mortality in transfused patientsAdjusted Odds Ratio 4.26 (2.25–8.08)Adjusted Odds Ratio 4.26 (2.25–8.08)

Transfusion Post PCI:Transfusion Post PCI:REPLACE 2 One Year MortalityREPLACE 2 One Year Mortality

1.9%

13.9%

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

14.0%

16.0%

Non-Transfused Transfused

P<0.0001

Manoukian SV, Voeltz MD, Attubato MJ, Bittl JA, Feit F, Lincoff AM. CRT 2005. Abstract.

► Although there has never been a randomized trial of blood transfusion in patients with ACS, the available observational data consistently supports a relationship between blood transfusion and increased adverse outcomes, including death, MI, and unplanned revascularization

► Blood transfusion is best avoided in ACS patients whenever possible

► Although there has never been a randomized trial of blood transfusion in patients with ACS, the available observational data consistently supports a relationship between blood transfusion and increased adverse outcomes, including death, MI, and unplanned revascularization

► Blood transfusion is best avoided in ACS patients whenever possible

Blood Transfusion—Conclusions

Are there certain ACS subpopulations

at especially high risk for bleeding,

transfusion, and morbidity/mortality?

Are there certain ACS subpopulations

at especially high risk for bleeding,

transfusion, and morbidity/mortality?

Bleeding in ACS


4.5

10.3

14.1

18.517.9

9.7

0

5

10

15

20

<65 yrs 65–75 yrs > 75 yrs

% R

BC

Tra

nsf

usi

on

Non-CABG Overall

Bleeding Risks—Transfusions by AgeBleeding Risks—Transfusions by Age

Alexander KA, Alexander KA, JAMAJAMA 2005;294:3108–16. 2005;294:3108–16. Alexander KA, Alexander KA, JAMAJAMA 2005;294:3108–16. 2005;294:3108–16.

6,002 patients in REPLACE-26,002 patients in REPLACE-2806 patients (13.4%) classified as elderly, >75 years of age806 patients (13.4%) classified as elderly, >75 years of age

p<0.0001 p=0.0001

2.7%

1.7%

5.0%

6.7%

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

8.0%

Major Bleeding Transfusions

REPLACE-2:REPLACE-2:Elderly Patients Have Increased Major Bleeding and Elderly Patients Have Increased Major Bleeding and

TransfusionsTransfusions

= Not Elderly, <75

= Elderly, >75

Voeltz MD, Lincoff AM, Feit F, Manoukian SV. Circulation 2005;112(17):II-613. Abstract.

0.5%0.4%

13.0%

15.0%

0.0%

2.0%

4.0%

6.0%

8.0%

10.0%

12.0%

14.0%

16.0%

18.0%

Major Bleeding Transfusions

30

-Da

y M

ort

ali

ty

No

Yes

p<0.0001 p=0.0001

6,002 patients in REPLACE-2.6,002 patients in REPLACE-2. 806 patients (13.4%) classified as elderly, >75 years of age.806 patients (13.4%) classified as elderly, >75 years of age.

Elderly Patients in REPLACE-2:Elderly Patients in REPLACE-2:Increased 30-Day Mortality With Major Bleeding and TransfusionsIncreased 30-Day Mortality With Major Bleeding and Transfusions

Voeltz MD, Lincoff AM, Feit F, Manoukian SV. Circulation 2005;112(17):II-613. Abstract.

Excessive Dosing ofExcessive Dosing ofAnticoagulants by AgeAnticoagulants by Age


12.5

28.7

8.5

33.137

12.5

64.5

38.5

16.5

0

10

20

30

40

50

60

70

LMW Heparin UF Heparin GP Iib/IIIa

% R

BC

Tra

nsf

usi

on

<65 yrs 65Š75 yrs >75 yrs

RBC Transfusions by Excess DosingRBC Transfusions by Excess Dosing

8

6.7

4.4

13.3

8.8

10.4

0

3

6

9

12

15

UF Heparin LMWH GP llb-llla

% R

BC

Tra

nsf

usi

on

Recommended Excess


Cumulative Effects of Dosing Errors: Cumulative Effects of Dosing Errors: Combined Use of Heparin and GP IIb-IIIaCombined Use of Heparin and GP IIb-IIIa

4.1

9

18.5

0

5

10

15

20

Both Right 1 Excessive Both Excessive

% R

BC

Tra

nsf

usi

on


Excess Dosing of Gp IIb/IIIa Excess Dosing of Gp IIb/IIIa and Bleeding in Womenand Bleeding in Women

OverallOverallOverallOverall

WomenWomenWomenWomen

MenMenMenMen

1.46 (1.22, 1.73)1.46 (1.22, 1.73)1.46 (1.22, 1.73)1.46 (1.22, 1.73)

1.72 (1.30, 2.28)1.72 (1.30, 2.28)1.72 (1.30, 2.28)1.72 (1.30, 2.28)

1.27 (0.97, 1.66)1.27 (0.97, 1.66)1.27 (0.97, 1.66)1.27 (0.97, 1.66)

0.50.50.50.5 1.01.01.01.0 1.51.51.51.5 2.02.02.02.0 2.52.52.52.5

Excess Dosing More Likely to BleedExcess Dosing More Likely to BleedExcess Dosing More Likely to BleedExcess Dosing More Likely to Bleed

Alexander KP, et. al. Circulation 2006Alexander KP, et. al. Circulation 2006

N=32,601 patients from CRUSADEN=32,601 patients from CRUSADEN=32,601 patients from CRUSADEN=32,601 patients from CRUSADE

Bleeding is Increased in Patients With Bleeding is Increased in Patients With Impaired Renal Function Undergoing PCIImpaired Renal Function Undergoing PCI

≥≥ 60 ml/min60 ml/min N=4824 N=4824

< 60 ml/min< 60 ml/min N=886 N=886 p valuep value

30-d Death30-d Death 5 (0.1%)5 (0.1%) 14 (1.6%)14 (1.6%) < 0.001< 0.001

30-d Myocardial infarction30-d Myocardial infarction 305 (6.3%)305 (6.3%) 75 (8.5%)75 (8.5%) 0.0180.018

30-d urgent revascularization30-d urgent revascularization 61 (1.3%)61 (1.3%) 10 (1.1%)10 (1.1%) 0.7380.738

Triple ischemic endpointTriple ischemic endpoint 338 (7.0%)338 (7.0%) 84 (9.5%)84 (9.5%) 0.0100.010

In-hospital protocol major In-hospital protocol major bleedingbleeding 123 (2.5%)123 (2.5%) 54 (6.1%)54 (6.1%) < 0.001< 0.001

TIMI major + minor bleedingTIMI major + minor bleeding 114 (2.4%)114 (2.4%) 46 (5.2%)46 (5.2%) < 0.001< 0.001

Creatinine ClearanceCreatinine Clearance

Chew DP et al. Am J Cardiol 2005;95:581–585.

Anemia Identifies High-RiskAnemia Identifies High-RiskThe Unrecognized Risk FactorThe Unrecognized Risk Factor

► OlderOlder

► FemaleFemale

► Lower BMILower BMI

► Fewer CaucasiansFewer Caucasians

► Lower Hemoglobin (11.7 vs. 14.3 g/dL)Lower Hemoglobin (11.7 vs. 14.3 g/dL)

► Lower Hematocrit (34.6 vs. 41.8%)Lower Hematocrit (34.6 vs. 41.8%)

► Less Tobacco useLess Tobacco use

► More Diabetes MellitusMore Diabetes Mellitus

► More history of CHF, MI, PCI, CABGMore history of CHF, MI, PCI, CABG

REPLACE-2 Anemic Patient Baseline Characteristics:REPLACE-2 Anemic Patient Baseline Characteristics:(Anemia in 22.7%)(Anemia in 22.7%)

Voeltz MD, Attubato MJ, Feit F, Lincoff AM, Manoukian SV. J Am Coll Cardiol 2005;45(3)[Suppl A]:1037-Voeltz MD, Attubato MJ, Feit F, Lincoff AM, Manoukian SV. J Am Coll Cardiol 2005;45(3)[Suppl A]:1037-13-31A. Abstract.13-31A. Abstract.

Major Bleeding is IncreasedMajor Bleeding is Increasedin Anemic Patients Undergoing PCIin Anemic Patients Undergoing PCI

0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

Non-Anemic Anemic

6,010 patients in REPLACE-2.1,362 patients (22.7%) classified as anemic based upon WHO definition.

Major bleeding = 3.2%

Major Bleeding

2.8%

4.9%

P=0.0001

Protocol definition: >3g/dL drop in HgB,

intracranial, retroperitoneal,

2U transfusion

Voeltz MD, Attubato MJ, Feit F, Lincoff AM, Manoukian SV. J Am Coll Cardiol 2005;45(3)[Suppl Voeltz MD, Attubato MJ, Feit F, Lincoff AM, Manoukian SV. J Am Coll Cardiol 2005;45(3)[Suppl A]:1037-13-31A. Abstract.A]:1037-13-31A. Abstract.

NSTE-ACS MortalityNSTE-ACS MortalityStratified by HemoglobinStratified by Hemoglobin

Sabatine MS. Circulation 2005

UnadjustedUnadjusted

Hb (g/dL)Hb (g/dL) nn OROR (95% Cl)(95% Cl) OROR (95% Cl)(95% Cl) P P valuevalue

>17>17 216 216 1.471.47 (1.03–2.10)(1.03–2.10) 1.451.45 (0.94–2.23)(0.94–2.23) 0.0930.093

16–1716–17 812 812 1.211.21 (0.97–1.51)(0.97–1.51) 1.271.27 (0.98–1.65)(0.98–1.65) 0.0660.066

15–1615–16 21302130 1.0 1.0 referencereference 1.0 1.0 referencereference

14–1514–15 33903390 1.061.06 (0.89–1.22)(0.89–1.22) 1.111.11 (0.93–1.33)(0.93–1.33) 0.2510.251

13–1413–14 35203520 1.021.02 (0.88–1.19)(0.88–1.19) 1.041.04 (0.86–1.24)(0.86–1.24) 0.7090.709

12–1312–13 23312331 1.091.09 (0.92–1.28)(0.92–1.28) 1.071.07 (0.88–1.30)(0.88–1.30) 0.5140.514

11–1211–12 976 976 1.201.20 (0.97–1.47)(0.97–1.47) 1.041.04 (0.81–1.34)(0.81–1.34) 0.7550.755

10–1110–11 343 343 1.411.41 (1.05–1.89)(1.05–1.89) 1.291.29 (0.92–1.82)(0.92–1.82) 0.1450.145

9–109–10 342 342 2.442.44 (1.88–3.18)(1.88–3.18) 2.692.69 (2.01–3.60)(2.01–3.60) <0.001<0.001

8–98–9 306 306 2.242.24 (1.69–2.96)(1.69–2.96) 2.452.45 (1.80–3.33)(1.80–3.33) <0.001<0.001

<8<8 137 137 3.973.97 (2.76–5.70)(2.76–5.70) 3.493.49 (2.35–5.20)(2.35–5.20) <0.001<0.001

Abbreviations: CI, confidence interval; Hb, hemoglobin; OR, odds ration. Adapted with permission.Abbreviations: CI, confidence interval; Hb, hemoglobin; OR, odds ration. Adapted with permission.

Unadjusted and adjusted odds ratios for cardiovascular mortality in patientsUnadjusted and adjusted odds ratios for cardiovascular mortality in patientswith non-ST elevation acute coronary syndromes at 30 days stratefied by hemoglobinwith non-ST elevation acute coronary syndromes at 30 days stratefied by hemoglobin

Adjusted for baseline characteristicsAdjusted for baseline characteristics

► Certain ACS patient populations are at especially high risk for bleeding and mortality

Elderly, females, CKD, anemia

► Improper dosing of anticoagulants is a common error and is associated with bleeding risk in the elderly, females, and those with CKD

► Anemia places patients at risk for both bleeding and mortality

► Certain ACS patient populations are at especially high risk for bleeding and mortality

Elderly, females, CKD, anemia

► Improper dosing of anticoagulants is a common error and is associated with bleeding risk in the elderly, females, and those with CKD

► Anemia places patients at risk for both bleeding and mortality

High-Risk Populations—Conclusions

Does bleeding influence the cost of

care for patients with ischemic heart

disease?

Does bleeding influence the cost of

care for patients with ischemic heart

disease?

Bleeding in ACS


8800

27349

1300

5900

0

10000

20000

30000

$$$

Urgent PCI UrgentCABG

Minor bleed Major bleed

Costs Abciximab versus Placebo

ischemic costs: $523

major bleed costs: $458

Abciximab versus Placebo

ischemic costs: $523

major bleed costs: $458

Mark DB, et al. Mark DB, et al. CirculationCirculation. 2000 Feb 1;101(4):366-71 . 2000 Feb 1;101(4):366-71 Mark DB, et al. Mark DB, et al. CirculationCirculation. 2000 Feb 1;101(4):366-71 . 2000 Feb 1;101(4):366-71

Calculating Costs of Ischemia and Bleeding:Calculating Costs of Ischemia and Bleeding:EPIC EQOL Study (Abciximab in PCI)EPIC EQOL Study (Abciximab in PCI)

► The available costs data confirms that a balance must be struck between ischemia reduction and bleeding.

► Both ischemic complications and bleeding are associated with increased costs.

► The available costs data confirms that a balance must be struck between ischemia reduction and bleeding.

► Both ischemic complications and bleeding are associated with increased costs.

Bleeding and Costs—Conclusions

Bleeding Among Patients with ACSBleeding Among Patients with ACSConclusionsConclusions

► Antithrombotic therapies are cornerstone RxAntithrombotic therapies are cornerstone Rx Must balance thrombosis and hemostasisMust balance thrombosis and hemostasis

► Certain patient and PCI procedure Certain patient and PCI procedure characteristics predict bleedingcharacteristics predict bleeding Age, female gender, CKD, procedure time, Age, female gender, CKD, procedure time,

sheath dwell timesheath dwell time

► Diabetes and anemia are newly identified risk Diabetes and anemia are newly identified risk factors for bleeding among ACS patientsfactors for bleeding among ACS patients

Conclusions—Bleeding Conclusions—Bleeding

►Bleeding is associated with worse short and Bleeding is associated with worse short and long-term outcomes including death and MIlong-term outcomes including death and MI

►Assessing bleeding severity is important Assessing bleeding severity is important

► Many definitions have been usedMany definitions have been used

► Definitions that include clinical events Definitions that include clinical events appear to be more useful than those that appear to be more useful than those that include only laboratory parametersinclude only laboratory parameters

►Blood transfusion is associated with increased Blood transfusion is associated with increased mortality in ACS patients mortality in ACS patients

►Bleeding is associated with worse short and Bleeding is associated with worse short and long-term outcomes including death and MIlong-term outcomes including death and MI

►Assessing bleeding severity is important Assessing bleeding severity is important

► Many definitions have been usedMany definitions have been used

► Definitions that include clinical events Definitions that include clinical events appear to be more useful than those that appear to be more useful than those that include only laboratory parametersinclude only laboratory parameters

►Blood transfusion is associated with increased Blood transfusion is associated with increased mortality in ACS patients mortality in ACS patients

Conclusions—Bleeding Conclusions—Bleeding

► In addition to clinical outcomes, bleeding is In addition to clinical outcomes, bleeding is associated with increased cost of careassociated with increased cost of care

► Bleeding costs can offset the savings Bleeding costs can offset the savings realized by reduced ischemic realized by reduced ischemic complicationscomplications

►Given the body of evidence related to bleeding Given the body of evidence related to bleeding and transfusion, therapies that can reduce and transfusion, therapies that can reduce ischemia while minimizing the risk for bleeding ischemia while minimizing the risk for bleeding have the potential to further improve outcomes have the potential to further improve outcomes among patients with ACSamong patients with ACS

► In addition to clinical outcomes, bleeding is In addition to clinical outcomes, bleeding is associated with increased cost of careassociated with increased cost of care

► Bleeding costs can offset the savings Bleeding costs can offset the savings realized by reduced ischemic realized by reduced ischemic complicationscomplications

►Given the body of evidence related to bleeding Given the body of evidence related to bleeding and transfusion, therapies that can reduce and transfusion, therapies that can reduce ischemia while minimizing the risk for bleeding ischemia while minimizing the risk for bleeding have the potential to further improve outcomes have the potential to further improve outcomes among patients with ACSamong patients with ACS

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Thomas Amidon, MDMedical DirectorThe Hope Heart InstituteOverlake Internal Medicine AssociatesSeattle, WA

Atul Aggarwal, MDNebraska Heart InstituteLincoln, NE

Himanshu Aggarwal, MDNebraska Heart InstituteSt. Frances Med CenterGrand Island, NE

Keith Benzuly, MD, FACCAssistant Professor of MedicineBluhm Cardiovascular InstituteNorthwestern UniversityFeinberg School of MedicineChicago, IL

ACS Faculty Review CommitteeACS Faculty Review Committee

Joseph J. Brennan Jr., MDAssociate Professor of Medicine, CardiologyDirector, Interventional Fellowship ProgramYale University School of MedicineNew Haven, CT

Carl Chudnofsky, MDChairmanDepartment of Emergency MedicineAlbert Einstein Medical CenterPhiladelphia, PA

Michael J. Cowley, MDProfessorDepartment of Internal MedicineDivision of CardiologyMedical College of VirginiaVirginia Commonwealth UniversityRichmond, VA

Harold Dauerman, MDDirector, Cardiovascular Catheterization

LaboratoryProfessor of MedicineFletcher Allen Health CareUniversity of Vermont College of MedicineBurlington, VT

William J. French, MDMedical DirectorCatheterization LaboratoryUCLA Medical CenterLos Angeles, CA

Satyendra Giri, MDSection ChiefVascular Medicine ProgramBaystate Health SystemsSpringfield, MA


Paul A. Gurbel, MDHelen Dalsheimer Director of the Division of

Cardiologyat Sinai Hospital of BaltimoreAssociate Professor of MedicineDivision of CardiologyJohns Hopkins University School of MedicineBaltimore, MD

Tim Henry, MDMinneapolis Heart Institute FoundationAssociate ProfessorUniversity of Minnesota School of MedicineMinneapolis, MD

Kurt Kleinschmidt, MDAssociate ProfessorDirector of Toxicology Fellowship ProgramUT Southwestern Medical CenterDallas, TX

James Leggett, MDAssociate Medical DirectorHope Heart InstituteSeattle, WA

Glen Levine, MDDirector, Cardiac Catheterization LabAssociate Professor of MedicineBaylor College of MedicineChief, Critical Cardiac CareHouston VA Medical CenterHouston, TX

John J. Lopez, MDAssociate Professor of MedicineDirectorCardiac Catheterization and Interventional CardiologyUniversity of ChicagoChicago, IL

Reginald Low, MDChief, Division of Cardiovascular MedicineUniversity of California, DavisDavis, CA


Barry L. Molk, MD, FACCAssociate Clinical ProfessorUniversity of Colorado Health Science CenterAurora Denver Cardiology AssociatesDenver, CO

Reynaldo Mulingtapang, MDAssistant Professor of MedicineDirector, University of South Florida

Interventional Cardiology ProgramTampa, FL

Robert A. Mulliken, MDMedical Director, Emergency DepartmentUniversity of Chicago HospitalsAssociate ProfessorUniversity of Chicago School of MedicineChicago, IL

Sandeep Nathan, MD, FACCAssistant Professor of MedicineRush Medical College, Section of CardiologyRush University Medical CenterDirector, Cardiovascular InterventionChicago, IL

Robert N. Piana, MDAssociate Professor of MedicineVanderbilt University School of MedicineDirector, Cardiac Catheterization LaboratoriesNashville, TN

Vincent J. Pompili, MD, FACCDirector of Interventional CardiologyUniversity HospitalsAssociate Professor of MedicineCase School of MedicineCleveland, OH

Matthew J. Price, MDDirectorCardiac Catheterization LaboratoryScripps ClinicDivision of Cardiovascular DiseasesLa Jolla, CA

David J. Robinson, MD, MS, FACEPAssociate Professor, Research Director and

Vice-ChairDept. of Emergency MedicineUniversity of Texas Health Sciences CenterHouston, TX


Joseph F. Stella, DO, FACCHeart Care Centers of IllinoisClinical Assistant ProfessorLoyola University Medical CenterChicago, IL

Paul E. Pepe, MD, MPHRiggs Family Chair in Emergency MedicineProfessor and Division ChairmanEmergency MedicineUniversity of Texas Southwestern Medical

CenterDallas, TX

Douglas J. Spriggs, MD, FACCClinical Assistant ProfessorDepts. of Internal Medicine and Family PracticeUniversity of South Florida College of MedicineClearwater Cardiovascular and Interventional ConsultantsClearwater, FL


Lowell H. Steen, Jr., MDAssociate Professor of Medicine, CardiologyLoyoyla University ChicagoStritch School of Medicine

Rex J. Winters, MDDirector of Invasive CardiologyLong Beach Memorial Heart Institute

Thomas Amidon, MD: Thomas Amidon, MD: Nothing to disclose.Nothing to disclose.

Atul Aggarwal, MD: Atul Aggarwal, MD: Grant/Research Support: Aventis, Schering-PloughGrant/Research Support: Aventis, Schering-Plough

Himanshu Aggarwal, MD: Himanshu Aggarwal, MD: Nothing to disclose.Nothing to disclose.

Keith Benzuly, MD, FACC: Keith Benzuly, MD, FACC: Speaker’s Bureau: The Medicines CompanySpeaker’s Bureau: The Medicines Company

Joseph J. Brennan Jr., MD: Joseph J. Brennan Jr., MD: Nothing to disclose.Nothing to disclose.

Carl Chudnofsky, MD: Carl Chudnofsky, MD: Nothing to discloseNothing to disclose..

Michael J. Cowley, MD: Michael J. Cowley, MD: Nothing to disclose.Nothing to disclose.

Harold Dauerman, MD: Harold Dauerman, MD: Grant/Research Support: Boston Scientific, Guidant. Consultant: The Grant/Research Support: Boston Scientific, Guidant. Consultant: The Medicines Company, Arginox.Medicines Company, Arginox.

William J. French, MD: William J. French, MD: Nothing to disclose.Nothing to disclose.

Satyendra Giri, MD: Satyendra Giri, MD: Nothing to disclose.Nothing to disclose.

Paul A. Gurbel, MD: Paul A. Gurbel, MD: Grant/Research Support: Schering-Plough, Millennium, AstraZeneca, Bayer, Grant/Research Support: Schering-Plough, Millennium, AstraZeneca, Bayer, Haemoscope, NIH, Medtronic, Boston ScientificHaemoscope, NIH, Medtronic, Boston Scientific

Thomas Amidon, MD: Thomas Amidon, MD: Nothing to disclose.Nothing to disclose.

Atul Aggarwal, MD: Atul Aggarwal, MD: Grant/Research Support: Aventis, Schering-PloughGrant/Research Support: Aventis, Schering-Plough

Himanshu Aggarwal, MD: Himanshu Aggarwal, MD: Nothing to disclose.Nothing to disclose.

Keith Benzuly, MD, FACC: Keith Benzuly, MD, FACC: Speaker’s Bureau: The Medicines CompanySpeaker’s Bureau: The Medicines Company

Joseph J. Brennan Jr., MD: Joseph J. Brennan Jr., MD: Nothing to disclose.Nothing to disclose.

Carl Chudnofsky, MD: Carl Chudnofsky, MD: Nothing to discloseNothing to disclose..

Michael J. Cowley, MD: Michael J. Cowley, MD: Nothing to disclose.Nothing to disclose.

Harold Dauerman, MD: Harold Dauerman, MD: Grant/Research Support: Boston Scientific, Guidant. Consultant: The Grant/Research Support: Boston Scientific, Guidant. Consultant: The Medicines Company, Arginox.Medicines Company, Arginox.

William J. French, MD: William J. French, MD: Nothing to disclose.Nothing to disclose.

Satyendra Giri, MD: Satyendra Giri, MD: Nothing to disclose.Nothing to disclose.

Paul A. Gurbel, MD: Paul A. Gurbel, MD: Grant/Research Support: Schering-Plough, Millennium, AstraZeneca, Bayer, Grant/Research Support: Schering-Plough, Millennium, AstraZeneca, Bayer, Haemoscope, NIH, Medtronic, Boston ScientificHaemoscope, NIH, Medtronic, Boston Scientific

ACS Review Committee Financial DisclosuresACS Review Committee Financial Disclosures

Tim Henry, MD: Tim Henry, MD: Nothing to disclose.Nothing to disclose.

Kurt Kleinschmidt, MD: Kurt Kleinschmidt, MD: Consultant:Consultant: The Medicines Company. Speaker’s Bureau: sanofi-aventis.The Medicines Company. Speaker’s Bureau: sanofi-aventis.

James Leggett, MD: James Leggett, MD: Grant/Research Support: The Medicines Company, sanofi-aventisGrant/Research Support: The Medicines Company, sanofi-aventis

Glenn Levine, MD: Glenn Levine, MD: Speaker’s Bureau: sanofi-aventisSpeaker’s Bureau: sanofi-aventis

John J. Lopez, MD: John J. Lopez, MD: Nothing to disclose.Nothing to disclose.

Reginald Low, MD: Reginald Low, MD: Nothing to disclose.Nothing to disclose.

Roberto Medina, MD:Roberto Medina, MD: Speaker’s Bureau: The Medicines Company Speaker’s Bureau: The Medicines Company

Barry L. Molk, MD, FACC: Barry L. Molk, MD, FACC: Nothing to disclose.Nothing to disclose.

Reynaldo Mulingtapang, MD: Reynaldo Mulingtapang, MD: Grant/Research Support: GlaxoSmithKline. Consultant: Medtronic AAA, Grant/Research Support: GlaxoSmithKline. Consultant: Medtronic AAA, Abbott. Speaker’s Bureau: Pfizer. Major Shareholder: Vascular Architects.Abbott. Speaker’s Bureau: Pfizer. Major Shareholder: Vascular Architects.

Robert A. Mulliken, MD: Robert A. Mulliken, MD: Nothing to disclose.Nothing to disclose.

Sandeep Nathan, MD, FACC: Sandeep Nathan, MD, FACC: Research Support: Guilford. Speaker’s Bureau: The Medicines Company, Research Support: Guilford. Speaker’s Bureau: The Medicines Company, sanofi-aventis.sanofi-aventis.


Paul E. Pepe, MD, MPHPaul E. Pepe, MD, MPH: : Nothing to disclose.Nothing to disclose.

Robert N. Piana, MD: Robert N. Piana, MD: Speaker’s Bureau: sanofi-aventisSpeaker’s Bureau: sanofi-aventis

Vincent J. Pompili, MD, FACC: Vincent J. Pompili, MD, FACC: Major Shareholder: Arteriocyte, Inc.Major Shareholder: Arteriocyte, Inc.

Matthew J. Price, MD: Matthew J. Price, MD: Nothing to disclose.Nothing to disclose.

Douglas J. Spriggs, MD, FACC: Douglas J. Spriggs, MD, FACC: Nothing to disclose.Nothing to disclose.

Lowell H. Steen, Jr., MD: Lowell H. Steen, Jr., MD: Nothing to disclose.Nothing to disclose.

David J. Robinson, MD, MS, FACEPDavid J. Robinson, MD, MS, FACEP: : Nothing to disclose.Nothing to disclose.

Joseph F. Stella, DO, FACC: Joseph F. Stella, DO, FACC: Nothing to disclose.Nothing to disclose.

Rex J. Winters, MD: Rex J. Winters, MD: Consultant:Consultant: Cordis, Johnson & Johnson, Guidant. Speaker’s Bureau: Cordis, Johnson & Johnson, Guidant. Speaker’s Bureau: The Medicines Company.The Medicines Company.

Paul E. Pepe, MD, MPHPaul E. Pepe, MD, MPH: : Nothing to disclose.Nothing to disclose.

Robert N. Piana, MD: Robert N. Piana, MD: Speaker’s Bureau: sanofi-aventisSpeaker’s Bureau: sanofi-aventis

Vincent J. Pompili, MD, FACC: Vincent J. Pompili, MD, FACC: Major Shareholder: Arteriocyte, Inc.Major Shareholder: Arteriocyte, Inc.

Matthew J. Price, MD: Matthew J. Price, MD: Nothing to disclose.Nothing to disclose.

Douglas J. Spriggs, MD, FACC: Douglas J. Spriggs, MD, FACC: Nothing to disclose.Nothing to disclose.

Lowell H. Steen, Jr., MD: Lowell H. Steen, Jr., MD: Nothing to disclose.Nothing to disclose.

David J. Robinson, MD, MS, FACEPDavid J. Robinson, MD, MS, FACEP: : Nothing to disclose.Nothing to disclose.

Joseph F. Stella, DO, FACC: Joseph F. Stella, DO, FACC: Nothing to disclose.Nothing to disclose.

Rex J. Winters, MD: Rex J. Winters, MD: Consultant:Consultant: Cordis, Johnson & Johnson, Guidant. Speaker’s Bureau: Cordis, Johnson & Johnson, Guidant. Speaker’s Bureau: The Medicines Company.The Medicines Company.


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