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

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Accreditation Information
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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Instructions for Receiving Category 1 AMA
Credit Participants This SlideCAST is a
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Accreditation Information
Intended Audience This SlideCAST is designed
for interventional cardiologists, cardiologists,
and emergency medicine physicians, and other
healthcare providers caring for patients with
acute cardiovascular disease. Registration
Enrollment for this SlideCAST is
complimentary, and clinicians are invited to
participate in this CME-certified program and/or
share this invitation with other colleagues,
departmental staff members, and healthcare
professionals. Grantor Support Supported by
an independent educational grant from The
Medicines Company, Inc.
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Accreditation Information
Accreditation Information
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implemented in accordance with the Essential
Areas and Policies of the Accreditation Council
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physicians. Credit Designation Statement 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.
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Accreditation Information
Policy on Faculty And Provider Disclosure It is
the policy of the University of Massachusetts
Medical School to ensure fair balance,
independence, objectivity and scientific rigor in
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7
ACS Forum Leadership Panel
Deepak L. Bhatt, MD, FACC, FSCAI, FESC,
FACP Associate Director, Cleveland Clinic
Cardiovascular Coordinating Center Staff,
Cardiac, Peripheral, and Carotid
Intervention Associate Professor of
Medicine Department of Cardiovascular
Medicine Cleveland Clinic Foundation Frederick
Feit, MD, FACC Director Cardiac Catheterization
and Interventional Cardiology Bellevue Hospital
Center Associate Professor of Medicine New York
University School of Medicine New York, NY
Deborah Diercks, MD Assistant Professor of
Medicine Department of Emergency
Medicine University of California Davis,
California James Ferguson III, MD Associate
Director, Cardiology Research Texas Heart
Institute at St. Luke's Episcopal
Hospital Associate Professor Baylor College of
Medicine Clinical Assistant Professor University
of Texas Health Science Center at
Houston Christopher Granger, MD Associate
Professor of Medicine Director of Cardiac Care
Unit Division of Cardiovascular Medicine Duke
University Medical Center
8
ACS Forum Leadership Panel
Judd E. Hollander, MD Professor Clinical Research
Director Department of Emergency
Medicine University of Pennsylvania Philadelphia,
PA David M. Lang, DO, FACOEP, FACEP
Chief Emergency Medicine Mount Sinai Medical
Center Miami Beach, FL Steven V. Manoukian, MD,
FACC Director, Interventional Cardiology Emory-Cra
wford Long Hospital Emory University School of
Medicine President American Heart Association,
Atlanta Division Atlanta, GA
Ralph G. Nader, MD, FACC, FACP, FSCAI Co-Medical
Director Cardiovascular Labs at
Mount-Sinai/Miami Heart Miami, FL E. Magnus
Ohman, MD, FRCPI, FACC Professor of
Medicine Director, Program for Advanced Coronary
Disease Division of Cardiology Duke University
Medical Center Durham, NC
9
ACS Forum Leadership Panel
Charles Pollack, MD, FACEP Chairman, Department
of Emergency Medicine Pennsylvania
Hospital Professor of Emergency
Medicine University of Pennsylvania School of
Medicine Philadelphia, PA Sunil V. Rao
MD Assistant Professor of Medicine Duke
University Medical Center Director, Cardiac
Catheterization Laboratories Durham VA Medical
Center Durham, NC
10
ACS Leadership Panel Financial Disclosures
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. Speakers 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. Speakers 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
11
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. Speakers 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 Speakers Bureau The Medicines
Company Charles Pollack, MD Grant/Research
Support GlaxoSmithKline. Consultant The
Medicines Company, Schering-Plough,
sanofi-aventis, BMS, Genentech. Speakers 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
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ACS Faculty Review Committee
Thomas Amidon, MD The Hope Heart Institute Atul
Aggarwal, MD Nebraska Heart Institute Himanshu
Aggarwal, MD Nebraska Heart Institute Keith
Benzuly, MD, FACC Northwestern University Joseph
J. Brennan Jr., MD Yale University School of
Medicine Carl Chudnofsky, MD Albert Einstein
Medical Center
Michael J. Cowley, MD Medical College of
Virginia Harold Dauerman, MD University of
Vermont William J. French, MD UCLA Medical
Center Satyendra Giri, MD Baystate Health
Systems Paul A. Gurbel, MD Johns Hopkins
University
Complete affiliations and financial disclosures
for Review Committee members are listed at end
of slide deck.
13
ACS Faculty Review Committee
Tim Henry, MD Minneapolis Heart Institute Kurt
Kleinschmidt, MD UT Southwestern Medical
Center James Leggett, MD Hope Heart
Institute Glenn Levine, MD Baylor College of
Medicine John J. Lopez, MD University of
Chicago Reginald Low, MD University of
California, Davis
Roberto Medina, MD Florida Medical Clinic Barry
L. Molk, MD, FACC University of Colorado
Reynaldo Mulingtapang, MD University of South
Florida Robert A. Mulliken, MD University of
Chicago Hospitals Sandeep Nathan, MD, FACC Rush
Medical College Paul E. Pepe, MD, MPH UT
Southwestern Medical Center
Complete affiliations and financial disclosures
for Review Committee members are listed at end of
slide deck.
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ACS Faculty Review Committee
David J. Robinson, MD, MS, FACEP UT Health
Sciences Center Joseph F. Stella, DO, FACC Heart
Care Centers of Illinois Rex J. Winters, MD Long
Beach Memorial Heart Institute
Robert N. Piana, MD Vanderbilt University
Vincent J. Pompili, MD, FACC Case School of
Medicine Matthew J. Price, MD Scripps
Clinic Douglas J. Spriggs, MD, FACC University
of South Florida Lowell H. Steen, Jr.,
MD Loyoyla University Chicago
Complete affiliations and financial disclosures
for Review Committee members are listed at end of
slide deck.
15
Educational Objectives

• 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.

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A Science-to-Strategy Analysis of Bleeding Issues
in Acute Coronary Syndromes

• BLEEDING IN THE SETTING OF
• ACUTE 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

17
(12 of total, 15 of those undergoing cath)
Surgery
CRUSADE Registry 10/04-9/05 n35,897
No disease
Medical Rx
(52 of total, 63 of those undergoing cath)
Medical Rx (cath)
PCI
(82 of total)
Cath
Patient X
Medical Rx (no cath)
(18 of total)
Medical Rx
Time
ACS Management Pathways
18
Milestones in ACS Management
ICTUS
ISAR-REACT 2
ACUITY
SYNERGY
1994
1995
1996
1997
1998
1999
2000
2002
2003
2004
2005
2006
2001
Ischemic risk
Bleeding risk
Adapted from and with the courtesy of Steven
Manoukian, MD.
19
Evolving Paradigm for Evaluating ACS Management
Strategies
Composite Adverse Event Endpoints

• Death
• MI
• Urgent TVR

Ischemic Complications
20
Evolving Paradigm for Evaluating ACS Management
Strategies
Composite Adverse Event Endpoints

• Major Bleeding
• Minor Bleeding
• Thrombocytopenia

• Death
• MI
• Urgent TVR

Ischemic Complications
Hemorrhage HIT
21
Evolving Paradigm for Evaluating ACS Management
Strategies
Composite Adverse Event Endpoints

• Cost
• Ease of Use
• Duration of Therapy
• Accounting for Bleeding and Ischemic Endpoints

• Death
• Major Disability

Periprocedural Complications
Clinical Benefit
22
Balancing Events and Bleeding
Risk of events
Risk of bleeding
Hemostasis
Thrombosis
Two sides of the same coin
23
CRUSADE In-Hospital Outcomes

• Death 4.3
• (Re)-Infarction 2.5
• CHF 8.0
• Cardiogenic Shock 2.6
• Stroke 0.8
• Non-CABG Transfusion 9.9

Bhatt DL, et al. JAMA. 2004 Nov
3292(17)2096-104.
24
Bleeding in ACS - Agenda

• Predictors of bleeding in ACS
• Outcomes associated with bleeding
• Impact of definition on outcomes
• Outcomes associated with blood transfusion
• Special populations at risk
• Elderly
• Chronic kidney disease
• Anemia
• Cost implications of bleeding

25
Bleeding in ACS
Question to be answered

• What predicts bleeding among patients with ACS ?

26
Predictors of Major Bleeding in ACS

• Older Age
• Female Gender
• Renal Failure
• History of Bleeding
• Right Heart Catheterization
• GPIIb-IIIa antagonists

Independent Predictors of Major Bleeding in
Marker Positive Acute Coronary Syndromes
Moscucci, GRACE Registry, Eur Heart J. 2003
Oct24(20)1815-23.
27
Predictors of Major Bleeding
Results The ACUITY Trial PCI Population
P-value
RR (95 CI)
Risk ratio 95 CI
Age gt75 (vs. 55-75)
Anemia
CrCl lt60mL/min
Diabetes
Female gender
High-risk (ST / biomarkers)
Hypertension
No prior PCI
Prior antithrombotic therapy
Heparin(s) GPI (vs. Bivalirudin)
1.56 (1.19-2.04) 0.0009
1.89 (1.48-2.41) lt0.0001
1.68 (1.29-2.18) lt0.0001
1.30 (1.03-1.63) 0.0248
2.08 (1.68-2.57) lt0.0001
1.42 (1.06-1.90) 0.0178
1.33 (1.03-1.70) 0.0287
1.47 (1.15-1.88) 0.0019
1.23 (0.98-1.55) 0.0768
2.08 (1.56-2.76) lt0.0001
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.
28
Predictors of Transfusion
Results The ACUITY Trial
P-value
RR (95 CI)
Risk ratio 95 CI
Age gt75 (vs. 55-75)
Anemia
CrCl lt60mL/min
Diabetes
Female gender
High-risk (ST / biomarkers)
Hypertension
Heparin(s) GPI (vs. Bivalirudin)
1.420 (1.055-1.910) 0.0060
3.764 (2.919-4.855) lt0.0001
2.097 (1.568-2.803) lt0.0001
1.560 (1.209-2.014) 0.0060
2.233 (1.739-2.867) lt0.0001
1.754 (1.297-2.372) 0.0003
1.457 (1.051-2.020) 0.0241
1.728 (1.256-2.379) 0.0007
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.
29
REPLACE-2Multivariate Predictors of Major
Bleeding
RISK FACTORS Odds Ratio 95 CI p-value
Baseline risk factors
Age gt 75 1.482 1.009 to 2.176 0.045
Gender (M vs. F) 0.652 0.477 to 0.890 0.0072
Prior Angina 1.589 1.077 to 2.345 0.0197
Creatinine clearance 0.993 0.987 to 0.998 0.0061
Anemia 1.403 1.015 to 1.939 0.0401

Peri-procedural risk factors
Treatment Group (BIV vs. HGPI) 0.508 0.352 to 0.733 0.0003
Provisional GPI received 2.679 1.591 to 4.512 0.0002
Procedure Duration gt1h 2.049 1.217 to 3.449 0.0069
Time to Sheath Removal gt6h 1.614 1.064 to 2.448 0.0244
ICU stay (days) 1.25 1.183 to 1.321 lt0.0001
IABP 8.705 3.433 to 22.072 lt0.0001
Feit F et al. Unpublished (in manuscript)
30
Bleeding PredictorsConclusions

• 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

31
Bleeding in ACS
Question to be answered

• Does bleeding influence the prognosis of ACS
  patients ?

32
Major Bleeding Predicts Mortality in ACS
24,045 ACS patients in the GRACE registry,
in-hospital death

Plt0.001
Patients ()
Overall Unstable NSTEMI
STEMI ACS Angina
Moscucci M et al. Eur Heart J 2003241815-23.
33
Bleeding Outcomes
Kaplan Meier Curves for 30-Day Death, Stratified
by Bleed Severity N26,452 ACS patients from
GUSTO IIb, PARAGON A, PARAGON B, PURSUIT
log rank p-value for all four categories
lt0.0001 log-rank p-value for no bleeding vs. mild
bleeding 0.02 log-rank p-value for mild vs.
moderate bleeding lt0.0001 log-rank p-value for
moderate vs. severe lt0.001
Rao SV, et al. Am J Cardiol. 2005 Nov
196(9)1200-6. Epub 2005 Sep 12
34
Bleeding and Outcomes in NSTE ACS
26,452 patients from PURSUIT, PARAGON A, PARAGON
B, GUSTO IIb NST
Bleeding severity and adjusted hazard of death
Bleeding Severity 30d Death 30d Death/MI 6 mo.
Death Mild 1.6 1.3 1.4 Moderate
2.7 3.3 2.1 Severe 10.6 5.6 7.5 Bleeding as a
time-dependent covariate
plt0.0001
Rao SV, et al. Am J Cardiol. 2005 Nov
196(9)1200-6. Epub 2005 Sep 12
35
Major Bleeding, Ischemic Endpoints, and
Mortality
Results The ACUITY Trial PCI Population (N7,789)
Plt0.0001 for all
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.
36
Major Bleeding and Myocardial Infarction
Results The ACUITY Trial PCI Population (N7,789)
Plt0.0001 for all
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.
37
Major and Minor Bleeding in PCIBleeding
Increases Mortality and Events
10,974 patients undergoing PCI, Washington
Hospital Center, 1991-2000.
Bleeding Complication
In-Hospital Clinical Events Major (n588) Minor (n1,394) None (n8,992)
Death 7.5 1.8 0.6
Q-wave myocardial infarction 1.2 0.7 0.2
Non-Q-wave myocardial infarction 30.7 16.8 11.8
Repeat lesion angioplasty 1.9 0.8 0.3
Major adverse cardiac event 6.6 2.2 0.6
plt0.001 versus none plt0.001 versus
minor plt0.01 versus none plt0.05
versus minor
Kinnaird TD et al. AM J Cardiol 200392930-5.
38
Bleeding and OutcomesConclusions

• 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

39
Bleeding in ACS
Question to be answered

• How does one assess bleeding severity?

40
Bleeding Incidence in ACS Clinical Trials
Rao SV, et al. J Am Coll Cardiol. 2006 Feb
2147(4)809-16. Epub 2006 Jan 26
41
Bleeding Definitions

• TIMI Definition
• Major
• ICH
• Associated with Hgb decrease 5 g/dl or HCT
  decrease 15
• Minor
• Observed blood loss associated with Hgb decrease
  3 g/dl or HCT decrease 10
• No identifiable source but Hgb decrease 4 g/dl
  or HCT decrease 12
• Minimal
• Overt hemorrhage with Hgb drop lt 3 g/dl or HCT
  drop lt 9

Chesebro JH. Circulation 1987. Jul76(1)142-54.
42
Bleeding Definitions

• GUSTO Definition
• Severe or life threatening
• ICH or hemodynamic compromise requiring treatment
• Moderate
• Requiring transfusion
• Mild
• Not meeting criteria for Severe or Moderate

N Engl J Med. 1993 Nov 25329(22)1615-22.
Erratum in N Engl J Med 1994 Feb 17330(7)516
43
Bleeding Incidence Among 15,858 NSTEACS
Patients Impact of Definition
Rao SV, et al. J Am Coll Cardiol. 2006 Feb
2147(4)809-16. Epub 2006 Jan 26
44
Bleeding Scales Among NSTE ACS Patients
TIMI and GUSTO Adjusted Hazard of 30 d Death/MI
N15,858
Rao SV, et al. J Am Coll Cardiol. 2006 Feb
2147(4)809-16. Epub 2006 Jan 26
45
Bleeding DefinitionsConclusions

• 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

46
Bleeding in ACS
Questions to be answered

• Do blood transfusions have predictive value?
• Do blood transfusions correct negative impact of
  bleeding?

47
Transfusion in ACS
N24,111
30-Day Survival By Transfusion Group
Rao SV, et. al., JAMA 200429215551562
48
PRBC Transfusion Among NSTE ACS PatientsCox
Model for 30-day Death
N24,111
Rao SV, et. al., JAMA 200429215551562
Transfusion as a time-dependent covariate
49
Adjusted Risk of In-Hospital Outcomes By
Transfusion Status
N74,271 ACS patients from CRUSADE
Non-CABG patients only
Yang X, J Am Coll Cardiol 20054614905.
50
Transfusion, Ischemic Endpoints, and Mortality
Results The ACUITY Trial (N13,819)
Plt0.0001 for all
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.
51
Transfusion and Myocardial Infarction
Results The ACUITY Trial (N13,819)
Plt0.0001 for all
Manoukian SV, Voeltz MD, Feit F et al. TCT 2006.
52
Transfusion Post PCIREPLACE 2 One Year Mortality
Increased 1-year mortality in transfused
patients Adjusted Odds Ratio 4.26 (2.258.08)
Plt0.0001
Manoukian SV, Voeltz MD, Attubato MJ, Bittl JA,
Feit F, Lincoff AM. CRT 2005. Abstract.
53
Blood TransfusionConclusions

• 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

54
Bleeding in ACS
Question to be answered

• Are there certain ACS subpopulations at
  especially high risk for bleeding, transfusion,
  and morbidity/mortality?

55
Bleeding RisksTransfusions by Age
Alexander KA, JAMA 2005294310816.
56
REPLACE-2Elderly Patients Have Increased Major
Bleeding and Transfusions
6,002 patients in REPLACE-2 806 patients (13.4)
classified as elderly, gt75 years of age
plt0.0001
p0.0001
Voeltz MD, Lincoff AM, Feit F, Manoukian SV.
Circulation 2005112(17)II-613. Abstract.
57
Elderly Patients in REPLACE-2Increased 30-Day
Mortality With Major Bleeding and Transfusions
6,002 patients in REPLACE-2. 806 patients
(13.4) classified as elderly, gt75 years of age.
plt0.0001
p0.0001
Voeltz MD, Lincoff AM, Feit F, Manoukian SV.
Circulation 2005112(17)II-613. Abstract.
58
Excessive Dosing ofAnticoagulants by Age
64.5
70
60
50
38.5
37
40
33.1
28.7
RBC Transfusion
30
16.5
20
12.5
12.5
8.5
10
0
LMW Heparin
UF Heparin
GP Iib/IIIa
lt65 yrs
65Š75 yrs
gt75 yrs
Alexander KA, JAMA 2005294310816.
59
RBC Transfusions by Excess Dosing
Alexander KA, JAMA 2005294310816.
60
Cumulative Effects of Dosing Errors Combined
Use of Heparin and GP IIb-IIIa
Alexander KA, JAMA 2005294310816.
61
Excess Dosing of Gp IIb/IIIa and Bleeding in
Women
N32,601 patients from CRUSADE
Alexander KP, et. al. Circulation 2006
62
Bleeding is Increased in Patients With Impaired
Renal Function Undergoing PCI
Creatinine Clearance
60 ml/min N4824 lt 60 ml/min N886 p value
30-d Death 5 (0.1) 14 (1.6) lt 0.001
30-d Myocardial infarction 305 (6.3) 75 (8.5) 0.018
30-d urgent revascularization 61 (1.3) 10 (1.1) 0.738
Triple ischemic endpoint 338 (7.0) 84 (9.5) 0.010
In-hospital protocol major bleeding 123 (2.5) 54 (6.1) lt 0.001
TIMI major minor bleeding 114 (2.4) 46 (5.2) lt 0.001
Chew DP et al. Am J Cardiol 200595581585.
63
Anemia Identifies High-RiskThe Unrecognized Risk
Factor
REPLACE-2 Anemic Patient Baseline
Characteristics(Anemia in 22.7)

• Older
• Female
• Lower BMI
• Fewer Caucasians
• Lower Hemoglobin (11.7 vs. 14.3 g/dL)
• Lower Hematocrit (34.6 vs. 41.8)
• Less Tobacco use
• More Diabetes Mellitus
• More history of CHF, MI, PCI, CABG

Voeltz MD, Attubato MJ, Feit F, Lincoff AM,
Manoukian SV. J Am Coll Cardiol 200545(3)Suppl
A1037-13-31A. Abstract.
64
Major Bleeding is Increasedin Anemic Patients
Undergoing PCI
6,010 patients in REPLACE-2. 1,362 patients
(22.7) classified as anemic based upon WHO
definition. Major bleeding 3.2
4.9
P0.0001
2.8
Protocol definition gt3g/dL drop in HgB,
intracranial, retroperitoneal, 2U
transfusion
Major Bleeding
Voeltz MD, Attubato MJ, Feit F, Lincoff AM,
Manoukian SV. J Am Coll Cardiol 200545(3)Suppl
A1037-13-31A. Abstract.
65
NSTE-ACS MortalityStratified by Hemoglobin
Unadjusted and adjusted odds ratios for
cardiovascular mortality in patientswith non-ST
elevation acute coronary syndromes at 30 days
stratefied by hemoglobin
Unadjusted
Adjusted for baseline characteristics
Hb (g/dL) n OR (95 Cl) OR (95 Cl) P
value gt17 216 1.47 (1.032.10) 1.45 (0.942.23)
0.093 1617 812 1.21 (0.971.51) 1.27 (0.981.65
) 0.066 1516 2130 1.0 reference 1.0
reference 1415 3390 1.06 (0.891.22) 1.11 (0.93
1.33) 0.251 1314 3520 1.02 (0.881.19) 1.04 (0.
861.24) 0.709 1213 2331 1.09 (0.921.28) 1.07 (
0.881.30) 0.514 1112 976 1.20 (0.971.47) 1.04
(0.811.34) 0.755 1011 343 1.41 (1.051.89) 1.
29 (0.921.82) 0.145 910 342 2.44 (1.883.18)
2.69 (2.013.60) lt0.001 89 306 2.24 (1.692.96)
2.45 (1.803.33) lt0.001 lt8 137 3.97 (2.765.70)
3.49 (2.355.20) lt0.001 Abbreviations CI,
confidence interval Hb, hemoglobin OR, odds
ration. Adapted with permission.
Sabatine MS. Circulation 2005
66
High-Risk PopulationsConclusions

• 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

67
Bleeding in ACS
Question to be answered

• Does bleeding influence the cost of care for
  patients with ischemic heart disease?

68
Calculating Costs of Ischemia and
BleedingEPIC EQOL Study (Abciximab in PCI)
Abciximab versus Placebo ? ischemic costs 523 ?
major bleed costs 458
Mark DB, et al. Circulation. 2000 Feb
1101(4)366-71
69
Bleeding and CostsConclusions

• 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.

70
Bleeding Among Patients with ACSConclusions

• Antithrombotic therapies are cornerstone Rx
• Must balance thrombosis and hemostasis
• Certain patient and PCI procedure characteristics
  predict bleeding
• Age, female gender, CKD, procedure time, sheath
  dwell time
• Diabetes and anemia are newly identified risk
  factors for bleeding among ACS patients

71
ConclusionsBleeding

• Bleeding is associated with worse short and
  long-term outcomes including death and MI
• Assessing bleeding severity is important
• Many definitions have been used
• Definitions that include clinical events appear
  to be more useful than those that include only
  laboratory parameters
• Blood transfusion is associated with increased
  mortality in ACS patients

72
ConclusionsBleeding

• In addition to clinical outcomes, bleeding is
  associated with increased cost of care
• Bleeding costs can offset the savings realized by
  reduced ischemic complications
• Given the body of evidence related to bleeding
  and transfusion, therapies that can reduce
  ischemia while minimizing the risk for bleeding
  have the potential to further improve outcomes
  among patients with ACS

73
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74
ACS Faculty Review Committee
Thomas Amidon, MD Medical Director The Hope Heart
Institute Overlake Internal Medicine
Associates Seattle, WA Atul Aggarwal,
MD Nebraska Heart Institute Lincoln, NE Himanshu
Aggarwal, MD Nebraska Heart Institute St. Frances
Med Center Grand Island, NE Keith Benzuly, MD,
FACC Assistant Professor of Medicine Bluhm
Cardiovascular Institute Northwestern
University Feinberg School of Medicine Chicago,
IL
Joseph J. Brennan Jr., MD Associate Professor of
Medicine, Cardiology Director, Interventional
Fellowship Program Yale University School of
Medicine New Haven, CT Carl Chudnofsky,
MD Chairman Department of Emergency
Medicine Albert Einstein Medical
Center Philadelphia, PA Michael J. Cowley,
MD Professor Department of Internal
Medicine Division of Cardiology Medical College
of Virginia Virginia Commonwealth
University Richmond, VA
75
ACS Faculty Review Committee
Harold Dauerman, MD Director, Cardiovascular
Catheterization Laboratory Professor of
Medicine Fletcher Allen Health Care University of
Vermont College of Medicine Burlington,
VT William J. French, MD Medical
Director Catheterization Laboratory UCLA Medical
Center Los Angeles, CA Satyendra Giri,
MD Section Chief Vascular Medicine
Program Baystate Health Systems Springfield, MA
Paul A. Gurbel, MD Helen Dalsheimer Director of
the Division of Cardiology at Sinai Hospital of
Baltimore Associate Professor of
Medicine Division of Cardiology Johns Hopkins
University School of Medicine Baltimore, MD Tim
Henry, MD Minneapolis Heart Institute
Foundation Associate Professor University of
Minnesota School of Medicine Minneapolis,
MD Kurt Kleinschmidt, MD Associate
Professor Director of Toxicology Fellowship
Program UT Southwestern Medical Center Dallas, TX
76
ACS Faculty Review Committee
James Leggett, MD Associate Medical Director Hope
Heart Institute Seattle, WA Glen Levine,
MD Director, Cardiac Catheterization
Lab Associate Professor of Medicine Baylor
College of Medicine Chief, Critical Cardiac
Care Houston VA Medical Center Houston, TX John
J. Lopez, MD Associate Professor of
Medicine Director Cardiac Catheterization and
Interventional Cardiology University of
Chicago Chicago, IL Reginald Low, MD Chief,
Division of Cardiovascular Medicine University of
California, Davis Davis, CA
Barry L. Molk, MD, FACC Associate Clinical
Professor University of Colorado Health Science
Center Aurora Denver Cardiology
Associates Denver, CO Reynaldo Mulingtapang,
MD Assistant Professor of Medicine Director,
University of South Florida Interventional
Cardiology Program Tampa, FL Robert A. Mulliken,
MD Medical Director, Emergency Department Universi
ty of Chicago Hospitals Associate
Professor University of Chicago School of
Medicine Chicago, IL Sandeep Nathan, MD,
FACC Assistant Professor of Medicine Rush Medical
College, Section of Cardiology Rush University
Medical Center Director, Cardiovascular
Intervention Chicago, IL
77
ACS Faculty Review Committee
Robert N. Piana, MD Associate Professor of
Medicine Vanderbilt University School of
Medicine Director, Cardiac Catheterization
Laboratories Nashville, TN Vincent J. Pompili,
MD, FACC Director of Interventional
Cardiology University Hospitals Associate
Professor of Medicine Case School of
Medicine Cleveland, OH Matthew J. Price,
MD Director Cardiac Catheterization
Laboratory Scripps Clinic Division of
Cardiovascular Diseases La Jolla, CA David J.
Robinson, MD, MS, FACEP Associate Professor,
Research Director and Vice-Chair Dept. of
Emergency Medicine University of Texas Health
Sciences Center Houston, TX
Joseph F. Stella, DO, FACC Heart Care Centers of
Illinois Clinical Assistant Professor Loyola
University Medical Center Chicago, IL Paul E.
Pepe, MD, MPH Riggs Family Chair in Emergency
Medicine Professor and Division
Chairman Emergency Medicine University of Texas
Southwestern Medical Center Dallas, TX Douglas
J. Spriggs, MD, FACC Clinical Assistant
Professor Depts. of Internal Medicine and Family
Practice University of South Florida College of
Medicine Clearwater Cardiovascular and
Interventional Consultants Clearwater, FL
78
ACS Faculty Review Committee
Lowell H. Steen, Jr., MD Associate Professor of
Medicine, Cardiology Loyoyla University
Chicago Stritch School of Medicine Rex J.
Winters, MD Director of Invasive Cardiology Long
Beach Memorial Heart Institute
79
ACS Review Committee Financial Disclosures
Thomas Amidon, MD Nothing to disclose. Atul
Aggarwal, MD Grant/Research Support Aventis,
Schering-Plough Himanshu Aggarwal, MD Nothing
to disclose. Keith Benzuly, MD, FACC Speakers
Bureau The Medicines Company Joseph J. Brennan
Jr., MD Nothing to disclose. Carl Chudnofsky,
MD Nothing to disclose. Michael J. Cowley, MD
Nothing to disclose. Harold Dauerman, MD
Grant/Research Support Boston Scientific,
Guidant. Consultant The Medicines Company,
Arginox. William J. French, MD Nothing to
disclose. Satyendra Giri, MD Nothing to
disclose. Paul A. Gurbel, MD Grant/Research
Support Schering-Plough, Millennium,
AstraZeneca, Bayer, Haemoscope, NIH, Medtronic,
Boston Scientific
80
ACS Review Committee Financial Disclosures

Tim Henry, MD Nothing to disclose. Kurt
Kleinschmidt, MD Consultant The Medicines
Company. Speakers Bureau sanofi-aventis. James
Leggett, MD Grant/Research Support The
Medicines Company, sanofi-aventis Glenn Levine,
MD Speakers Bureau sanofi-aventis John J.
Lopez, MD Nothing to disclose. Reginald Low,
MD Nothing to disclose. Roberto Medina, MD
Speakers Bureau The Medicines Company Barry L.
Molk, MD, FACC Nothing to disclose. Reynaldo
Mulingtapang, MD Grant/Research Support
GlaxoSmithKline. Consultant Medtronic AAA,
Abbott. Speakers Bureau Pfizer. Major
Shareholder Vascular Architects. Robert A.
Mulliken, MD Nothing to disclose. Sandeep
Nathan, MD, FACC Research Support Guilford.
Speakers Bureau The Medicines Company,
sanofi-aventis.
81
ACS Review Committee Financial Disclosures

Paul E. Pepe, MD, MPH Nothing to
disclose. Robert N. Piana, MD Speakers Bureau
sanofi-aventis Vincent J. Pompili, MD, FACC
Major Shareholder Arteriocyte, Inc. Matthew J.
Price, MD Nothing to disclose. Douglas J.
Spriggs, MD, FACC Nothing to disclose. Lowell
H. Steen, Jr., MD Nothing to disclose. David J.
Robinson, MD, MS, FACEP Nothing to
disclose. Joseph F. Stella, DO, FACC Nothing to
disclose. Rex J. Winters, MD Consultant
Cordis, Johnson Johnson, Guidant. Speakers
Bureau The Medicines Company.
82
CME Test
Complimentary CME Test To access the
complimentary CME test, program participants must
have internet access. Participants can access
the on-line evaluation form and receive instant
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83
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