A Case-Based Presentation - CME Outfitters

Using Evidence
and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
A Free, Two-Hour
CME/CNE/CPE
Online Activity
Based on the live CE
symposium presented in
Chicago, IL, on March 29,
2008.
CME Outfitters gratefully acknowledges
an educational grant from Schering-Plough
Corporation in support of this CE activity.
This activity is not part of the official ACC Annual Scientific Session and/or the SCAI Annual Scientific Sessions in Partnership
with ACC i2 Summit as planned by their Program Committees.

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
MODERATOR/FACILITATOR
Christopher P. Cannon, MD
Senior Investigator, TIMI Study Group
Brigham and Women’s Hospital
Associate Professor of Medicine
Harvard Medical School
Boston, MA
FACULTY
Jeffrey L. Anderson, MD, FACC, FAHA, MACP
Associate Chief of Cardiology
Intermountain Medical Center
Co-Director of Cardiac Research
Professor of Internal Medicine
University of Utah
Salt Lake City, UT
Robert A. Harrington, MD
Professor of Medicine, Division of Cardiology
Duke University Medical Center
Director, Duke Clinical Research Institute
Durham, NC

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Statement of Need
Acute coronary syndrome (ACS) affects more than 1.5 million people in the United
States each year, and is associated with an increased risk of cardiac death. 1 Prevention
of cardiac events in patients with ACS and those with prior myocardial infarction (MI)
or stroke is crucial to improving outcomes and preventing death. Yet, almost half of all
patients are under-recognized and not adequately managed. The American College
of Cardiology/American Heart Association (ACC/AHA) have recently published new
treatment guidelines for ACS, yet even when guidelines are incorporated in practice,
some issues remain controversial. For instance, dosing and timing of the administration
of antithrombotic therapies is not consistent and these factors can impact outcome. 2 Also,
clinicians need to know the importance of risk stratification in the management of ACS. In
addition, short-term and long-term management strategies for ACS may differ, and there
is not yet consensus in the field regarding best practices. Although current antithrombotic
agents are effective, there is room for improvement in outcomes. 3 Promising new agents,
including PY212 inhibitors, thrombin receptor antagonists, and Factor Xa inhibitors may
play a key role in improving patient care. Faculty in this case-based activity will translate
the latest evidence on treatment guidelines and emerging management strategies to
improve practice, individualize treatments, and optimize outcomes of patients with ACS.
References:
1. Kaiyala E, et al. Emerg Med 2004;36:20-38.
2. Giugliano R, et al. Am Heart J 2006;149:994-1002.
3. Wiviott SD, et al. N Engl J Med 2007;357:2001-2015.
Activity Goal
The goal of this activity is to provide an overview of current and emerging treatment
strategies for patients with acute coronary syndrome.
Learning Objectives
• Describe the impact of treatment selection, dosing, and timing of antiplatelet therapies
on overall outcomes of patients with acute coronary syndrome.
• Recognize the role of antithrombotic therapy in the prevention and management of
acute coronary syndrome according to ACC/AHA guidelines.
• Evaluate emerging therapies in the management of patients with acute coronary
syndrome.
Target Audience
Cardiologists, physician assistants, nurses, nurse practitioners, pharmacists, and other
clinicians who treat patients with acute coronary syndrome.

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Commercial Support
CME Outfitters gratefully acknowledges an educational grant from Schering-Plough
Corporation in support of this CE activity.
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Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
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Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Disclosure Declaration
It is the policy of CME Outfitters, LLC, to ensure independence, balance, objectivity,
and scientific rigor and integrity in all its CE activities. Faculty must disclose to the
participants any significant relationships with commercial companies whose products or
devices may be mentioned in faculty presentations, or with the commercial supporter of
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evidence-based data/research, and a multidisciplinary peer review process. The following
information is for participant information only. It is not assumed that these relationships
will have a negative impact on the presentations.
Dr. Cannon has disclosed he receives grants/research support from Accumetrics,
AstraZeneca Pharmaceuticals, GlaxoSmithKline, Merck & Co., Inc., Merck & Co.,
Inc./Schering-Plough Corporation partnership, sanofi-aventis/Bristol-Myers Squibb
partnership, and Schering-Plough Corporation.
Dr. Anderson has disclosed he receives research support from AstraZeneca
Pharmaceuticals. He serves on the speakers bureau for Merck & Co., Inc., and serves as
a consultant for Eli Lilly and Company/CSI. He has received honorarium from Schering-
Plough Corporation.
Dr. Harrington has disclosed that the Duke Clinical Research Institute (DCRI), of which he
is the director, has received research grant/contracts from Abbott Vasc-Devices, Acorn
Cardiovascular, Actelion, Acusphere, Inc., Adolor Corporation, Advanced CV Systems,
Advanced Stent Technologies, Inc., Agilent Technologies, Inc., Ajinomoto Co., Inc.,
Alsius Corporation, Allergan, Inc., Amgen Inc., Amylin Pharmaceuticals Inc., Anadys
Pharmaceuticals, Inc., ANGES MG, Inc., Arginox Pharmaceuticals, Inc., Angiometrx
Inc., Ark Therapeutics Group plc, Astellas Pharma US, Inc., Astra Hassle, AstraZeneca
Pharmaceuticals, Atritech, Inc., Aventis, Avion Flumist, Baxter, Bayer AG, Bayer
Corporation, Berlex Laboratories, Biogen Idec, Bioheart, Inc., Biosense Webster, Inc.,
Biosite, Inc., Bio-Technology General, Boehringer-Ingelheim Pharmaceuticals, Inc., Boston
MedTech Advisors, Boston Scientific Corporation, Bristol-Myers Squibb Company, CanAm
Bioresearch Inc., Cardiac Science, Inc., CardioThoracic Systems, Inc., CardioDynamics
International, CardioKinetix Inc., Celsion Corporation, Centocor, Inc., Cerexa, Inc.,
Chugai Pharma USA, LLC, Cierra, Inc., Coley Pharma Group, Conor Medsystems, LLC.,
Corautus Genetics, Inc., Cordis Corporation, Corgentech, Covalent Group, Critical
Therapeutics, Inc., Cubist Pharmaceuticals, CV Therapeutics, Inc., Cytokinetics, Inc.,
Dade Behring, Daiichi, deCODE Genetics, Dyax Corp., Echosens, Inc., Eclipse Surgical
Technologies, Edwards Lifesciences, Eisai Pharmaceuticals, Eli Lilly and Company,
Enzon Pharmaceutical, EPI-Q, Inc., ev3, Inc., Evalve, Inc., First Circle Medical, Inc., First
Horizon, Flow Cardia, Inc., Fox Hollow Pharmaceutical, Fujisawa, Genentech, Inc.,
General Electric Healthcare, General Electric Medical Systems, Genzyme Corporation,

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Getz Bros, Co., Inc., Gilead Sciences, Inc., GlaxoSmithKline, Guidant, Guilford
Pharmaceuticals, Heartscape Technologies, Inc., Hoffmann-La Roche Inc., Human
Genome Sciences, Humana, iCo Therapeutics Inc., IDB Medical, Idenix Pharmaceuticals,
Inc., Idera Pharmaceuticals, Inc., Idun Pharmaceuticals, Inc., Immunex, INFORMD,
Inc., InfraReDx, Inc., Inhibitex, Inc., Innocoll Pharmaceuticals, INO Therapeutics,
Inc., Inspire Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Integrated Therapeutics
Group, InterMune Pharmaceuticals, Inverness Medical Innovations, Ischemix, Inc., ISIS
Pharmaceuticals, Inc., Johnson & Johnson, Jomed, Inc., KAI Pharmaceuticals, Kerberos
Proximal Inc., King Pharmaceuticals, Inc., Kuhera Chemical Co., Lumen Biomedical,
Meacoustics, Medicure Inc., Medicure MiniMed, Medi-Flex, Inc., MedImmune, Inc.,
Medtronic, Inc., Merck Co., & Inc., MicroMed Tech, Inc., Microphage, Inc., Millennium
Pharmaceutical, Mitsubishi, Momenta Pharmaceuticals, Inc., Mycosol, Inc., NABI
Biopharmaceuticals, Neuron Pharmaceuticals, Inc., NitroMed, Inc., NovaCardia, Inc.,
Novartis Pharmaceuticals Corporation, Organon International, Ortho Biotech Products,
LP, OSI Eyetech, Osiris Therapeutics, Inc., Otsuka America Pharmaceutical, Inc.,
Pathway Medical Technologies, Inc., PDL BioPharma, Inc., Pfizer Inc., Pharmanetics,
Inc., Pharmassest, Inc., Pharsight Corporation, Portola Pharmaceuticals, Inc., Proctor
& Gamble, Prometheus Laboratories Inc., Purdue Pharma LP, Radiant Pharma,
Recom Managed Systems, Regado Biosciences, Inc., Reliant Pharmaceuticals, LLC,
Roche Diagnostic Corp., Roche Labs, Salix Pharmaceuticals, sanofi-pasteur, sanofiaventis,
sanofi-synthelabo, Schering-Plough Corporation, SciClone Pharmaceuticals,
Inc., Scios Inc., Searle Pharmaceutical Products, Sicel Technologies, Inc., Siemens,
Social Scientific Systems, Inc., Spectranetics Corporation, Summit Pharmaceuticals
International Corporation, Sunesis Pharmaceuticals, Inc., TAP Pharmaceutical Products
Inc., Terumo Corporation, The Medicines Company, Theravance, Inc., TherOx, Inc.,
Thoratec Corporation, Titan Pharmaceuticals, Inc., United Therapeutics, Uptake Medical
Corp., Valeant Pharmaceuticals International, Valentis, Inc., Vascular Solutions, Inc.,
Velocimed Inc., Veridex, LLC, Vertex Pharmaceuticals, Viasys Healthcare, Inc., Vicuron
Pharmaceuticals Inc., Wyeth Pharmaceuticals, Wyeth-Ayerst, XOMA LLC, Xsira
Pharmaceuticals, Inc., XTL Biopharmaceuticals Ltd., and Yamanouchi Pharma America,
Inc.
Dr. Harrington has received individual grant from Bristol-Myers Squibb Company, KAI
Pharmaceuticals, Medicure Inc., Millennium Pharmaceuticals, Inc., Proctor & Gamble,
and Schering-Plough Corporation. He has received research support (DCRI) from Bristol-
Myers Squibb Company and CanAm Bioresearch Inc. Dr. Harrington is on the speakers
bureaus of Schering-Plough Corporation with honorarium from Duke and serves as a
consultant to AstraZeneca Pharmaceuticals, Bristol-Myers Squibb Company, sanofiaventis,
Schering-Plough Corporation, Seredigm, and WebMD.

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Unlabeled Use Disclosure
Faculty of this CE activity may include discussions of products or devices that are
not currently labeled for use by the FDA. The faculty have been informed of their
responsibility to disclose to the audience if they will be discussing off-label or
investigational uses (any uses not approved by the FDA) of products or devices.
CME Outfitters, LLC, the faculty, and Schering-Plough Corporation do not endorse the use
of any product outside of the FDA labeled indications. Medical professionals should not
utilize the procedures, products, or diagnosis techniques discussed during this activity
without evaluation of their patient for contraindications or dangers of use.

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
GLOSSARY OF TERMS
∆
⊕
A/C
ACC
ACS
ADP
AHA
ALBION
AMI
ARC
ARMYDA-2
ASA
BID
Bival
BL
BMI
BMS
BP
cTn I
cTnT
CABG
CAD
Cath
CHF
Chg
Chol
CI
CK
CK-MB
CONS
CRUSADE
CV
CVA
d
DES
DM
E-Sel
Change, differences
Positive
Anticoagulant
American College of Cardiology
Acute Coronary Syndrome
Adenosine diphosphate
American Heart Association
Assessment of Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and
Ongoing Necrosis study
Acute myocardial infarction
Academic Research Consortium definition of stent thrombosis
Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty Study
Acetylsalicylic acid/aspirin
Twice daily dosing
Bivalirudin
Baseline
Body mass index
Bare metal stent
Blood pressure
Cardiac troponin I
Cardiac troponin T
Coronary artery bypass graft
Coronary Artery Disease
Catheter
Congestive Heart Failure
Change
Cholesterol
Confidence interval
Creatine kinase
Creatine kinase isoform MB
Conservative
Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with an
Early implementation of the ACC and AHA guidelines study
Cardiovascular
Cardiovascular accident
Day
Drug-eluting stent
Diabetes mellitus
e-selectin

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
ECG
ED
Enox
EP
Eze
FHx
Fonda
Electrocardiogram
Emergency Department
Enoxaparin
En point
Ezetimibe
Family history
Fondaparinux
FRISC-II The Framingham and fast Revascularization during InStability in Coronary artery disease - 5
year follow-up
GP IIb/IIIa
GPI
GPx
GRACE
HDL-C
HF
H-FABP
HTN
HR
hs-CRP
Hx
ICTUS
IL-6
IL-18
IMA
INV
IPA
ISAR-COOL
ISAR-Choice
Isch
LAD
LCx
LDL-C
LMWH
LOE
LV
LVEF
MACE
MCP-1
Glycoprotein IIb/IIIa
Glycoprotein IIb/IIIa inhibitor
Glutathione peroxidase
Global Registry of Acute Coronary Events
High density lipoprotein cholesterol
Heart failure
Heart-type fatty acid binding protein
Hypertension
Heart rate or hazard ratio
High sensitivity C-reactive protein
History
Invasive versus Conservative Treatment in Unstable Coronary Syndromes study
Interleukin-6
Interleukin-18
Ischemia-modified albumin
Invasive
Inhibition of platelet activity
Intracoronary Stenting with Antithrombotic Regimen - Cooling Off Trial
Intracoronary Stenting with Antithrombotic Regimen: Choose between 3 High Oral doses for
Immediate Clopidogrel Effect
Ischemia
Left anterior descending
Left circumflex artery
Low density lipoprotein cholesterol
Low molecular weight heparin
Level of evidence
Left ventricle
Left ventricular ejection fraction
Major adverse clinical endpoints
Monocyte chemoattractant protein-1

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
MMPs
MPO
Myo
MI
N
Nitro
NNT
NS
NSTE-ACS
NSTEMI
NT-proBNP
OASIS
OPUS-TIMI 16
OR
OxLDL
PAI-1
PAPP-A
PBO
PCI
PlGF
PK
Pop
PRISM PLUS
PTCA
Pts
PURSUIT
PVD
QD
QHS
QID
RCA
Rec
Ref
Refract
Rehosp
RI
RITA-3
Matrix metalloproteinase
Myeloperoxidase
Myoglobin
Myocardial infarction
Number of subjects
Nitroglycerin
Number needed to treat
Not statistically significant
Non-ST elevation acute coronary syndrome
Non-ST elevation myocardial infarction
N-terminal pro-B-type natriuretic peptide
Organization to Assess Strategies for Ischemic Syndromes Regisry
Orbofiban in Patients with Unstable coronary Syndromes – Thrombolysis In Myocardial
Infarction 16 study
Odds ratio
Oxidized LDL
Plasminogen activator inhibitor
Pregnancy associated plasma protein-A
Placebo
Percutaneous coronary intervention
Placental growth factor
Pharmacokinetics
Population
Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable
Signs and Symptoms study
Percutaneous transluminal coronary angioplasty
Patients
Platelet Glycoprotein IIb/IIIa in Unstable Angina Using Integrilin Therapy study
Peripheral Vascular Disease
Every day
Every night
Four times per day
Right coronary artery
Recurrent
Reference
Refractory
Rehospitalization
Re-infarction
Randomized Intervention Trial of Unstable Angina -- Long-term Impact of an Interventional
Strategy in Non-ST-Elevation ACS
10

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
RR
RRR
Rx
SA
SAA
SBP
sCD40L
sICAM-1
Simva
sVAM-1
TC
TF
TG
TIMI
TNFa
Tnl
TnT
t-PA
TRA
TRITON-TIMI 38
TRUCS
TVR
UA
uFFA
UFH
UTVR
VINO
vWF
Relative risk
Regular rate and rhythm
Prescription
Stable angina
Serum amyloid A
Systolic blood pressure
Soluble CD40 ligand
Soluble intracellular adhesion molecule-1
Simvastatin
Soluble vascular adhesion molecule-1
Total cholesterol
Tissue factor
Triglycerides
Thrombosis In Myocardial Infarction study
Tissue necrosis factor alpha
Troponin
Troponin T
Tissue-type plasminogen activator
Thrombin receptor antagonism
Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes:
design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing
platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 study
Treatment of Refractory Unstable angina in geographically isolated areas without Cardiac
Surgery study
Target vessel revascularization
Unstable angina
Unsaturated free fatty acids
Unfractionated heparin
Urgent
Value of First Day Angiography/Angioplasty in Evolving Non-ST elevation myocardial infarction:
An open multicenter randomized trial
von Willebrand factor
11

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Faculty Biographies
Christopher P. Cannon, MD
Dr. Cannon is an Associate Professor of Medicine at Harvard Medical School and an
Associate Physician in the Cardiovascular Division at Brigham and Women’s Hospital
in Boston. He is a senior investigator of the Thrombolysis in Myocardial Infarction (TIMI)
Study Group, leading trials such as TACTICS-TIMI 18, PROVE IT-TIMI 22, CLARITY-TIMI
28, and MEDAL.
He earned his medical degree from Columbia University College of Physicians and
Surgeons in New York, and after completing his residency in internal medicine at
Columbia Presbyterian Medical Center, he was a cardiovascular fellow at Brigham and
Women’s Hospital.
In addition to being a frequent lecturer, Dr. Cannon has published more than 500
original articles, reviews, editorials, book chapters, and electronic publications in the
field of acute coronary syndromes. His research is published in journals including
Circulation, Journal of the American College of Cardiology (ACC), Lancet, Journal of
the American Medical Association, and the New England Journal of Medicine. He
is Editor-in-Chief of the journal Critical Pathways in Cardiology and a 35-book series
Contemporary Cardiology. He is editor or author of 6 books. He is the new Editor-in-
Chief of the American College of Cardiology’s website Cardiosource (www.cardiosource.
com).
Dr. Cannon has received numerous awards including the Alfred Steiner Research Award,
Upjohn Achievement in Research Award, and Robert F. Loeb Award for Excellence
in Clinical Medicine. He is a fellow of the American Heart Association (AHA), and
the ACC. He serves as Chairman of the AHA’s Get With the Guidelines Science
Subcommittee, and of the ACC’s ACTION registry Steering Committee. He is the
principal investigator of several ongoing trials, including IMPROVE IT, which will evaluate
the benefit of lowering of LDL cholesterol well below 70 mg/dl with ezetimibe plus
simvastatin as compared simvastatin alone.
12

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Jeffrey L. Anderson, MD, FACC, FAHA, MACP
Dr. Anderson is Associate Chief of Cardiology, Co-Director of Cardiovascular Research,
Intermountain Medical Center, Intermountain Healthcare, and Professor of Internal
Medicine (with tenure) University of Utah. He is board certified in internal medicine,
cardiovascular disease, and clinical electrophysiology. Currently he is President-Elect, and
a member of the Executive Committee, Western States Division, of the American Heart
Association. Dr. Anderson is also Editor-in-Chief of Current Cardiovascular Reviews.
Dr. Anderson has Fellowships in several organizations, including the American Heart
Association and the American College of Cardiology, and is a Master of the American
College of Physicians. He served for 4 years on the US Food and Drug Administration’s
Cardiorenal Advisory Committee, where he was committee chair from 1994 to 1996. He
has been a frequent national and international lecturer on various topics in cardiology.
He has received many visiting professorships and is honorary professor of medicine at
Xi’an Medical School in Xi’an, China. He also has received several awards, including the
Golden Apple Award, Gold Caduceus Award (LDS Hospital), Laureate Award (American
College of Physicians) and the Heart of Gold Award (American Heart Association). Dr.
Anderson has contributed to a broad range of cardiovascular research and has chaired
or served on steering committees of numerous trials supported by the National Institutes
of Health, industry, and other local and national funding sources. He is an author or
co-author on over 500 original or invited publications, 370 abstracts, and 61 book
chapters. He is a frequent reviewer for most of the major cardiovascular and internal
medicine journals and has served on several editorial boards. Dr. Anderson graduated
with honors from Harvard Medical School and completed his residency in internal
medicine at Massachusetts General Hospital. He completed his postdoctoral fellowship in
cardiology at Stanford University.
13

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Robert A. Harrington, MD
Dr. Harrington is the Director of the Duke Clinical Research Institute (DCRI). Robert A.
Harrington, MD received his undergraduate degree in English from the College of the
Holy Cross, Worcester, MA. He attended Dartmouth Medical School and received
his medical degree from Tufts University School of Medicine in 1986. He was an
intern, resident and the Chief Medical Resident in internal medicine at the University of
Massachusetts Medical Center. He was a fellow in cardiology at Duke University Medical
Center, where he received training in interventional cardiology and research training
in the Duke Databank for Cardiovascular Diseases. He joined the Duke faculty in the
Division of Cardiology in 1993, where he is currently a Professor of Medicine and an
interventional cardiologist.
His research interests include evaluating antithrombotic therapies to treat acute ischemic
heart disease and to minimize the acute complications of percutaneous coronary
procedures, studying the mechanism of disease of the acute coronary syndromes,
understanding the issues of risk stratification in the care of patients with acute ischemic
coronary syndromes, trying to better understand and improve upon the methodology of
large clinical trials. He is the recipient of an NIH Roadmap contract to investigate “best
practices” among clinical trial networks.
He has authored multiple peer-reviewed manuscripts, reviews, book chapters, and
editorials. He is one of the senior co-editors for the 8th edition of the American College
of Chest Physicians’ Consensus Panel on Antithrombotic and Thrombolytic Drugs. He
is an Associate Editor of the American Heart Journal and an editorial board member
for the Journal of the American College of Cardiology. He is a Fellow of the American
College of Cardiology, the American Heart Association, the Society of Cardiovascular
Angiography and Intervention and the American College of Chest Physicians. He
currently chairs the American College of Cardiology Clinical Expert Consensus Document
Task Force and the Education Strategy Committee. He chaired the 2006 Annual Scientific
Sessions for the American College of Cardiology. He currently serves as a member of
the FDA Cardiovascular and Renal Drugs Advisory Committee, a member of the NHLBI’s
study section for clinical trials and as a member of the NHLBI Working Group on Clinical
Trials Methodology.
14

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Welcome/Introduction and Interactive Case Presentation #1
Using Evidence and
Guidelines to Individualize
Care for ACS:
A Case-Based Symposium
Supported by an unrestricted educational grant from
CME Outfitters, LLC,
is the accredited provider for
this continuing education
activity.
CME Outfitters gratefully
acknowledges an educational
grant from Schering-Plough
Corporation in support of this
CE activity.
5

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Welcome/Introduction and Interactive Case Presentation #1
The course guide for this
activity includes slides,
disclosures of faculty
financial relationships,
and biographical profiles.
For additional copies of these
materials, please visit
CMEoutfitters.com or call
877.CME.PROS.
To receive CE credits for this
activity, participants may either
complete the post-test and
evaluation online at
CMEoutfitters.com/test
or complete and submit both
a Credit Request Form and an
Activity Evaluation Form, which
are located in the Main Menu
under “Post-Test and
CE Credit Forms.”
The faculty have been
informed of their
responsibility to disclose
to the audience if they will
be discussing off-label
or investigational uses
(any use not approved
by the FDA) of products
or devices.
16

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Welcome/Introduction and Interactive Case Presentation #1
Welcome and
Introduction
Christopher P. Cannon, MD
Brigham and Women's Hospital
Harvard Medical School
Agenda
Risk Stratification and Choosing Strategy
– Case Presentation
– Christopher Cannon, MD
Treatment Guidelines: Evidence and
Application
– Case Presentation
– Jeffrey Anderson, MD
New Therapies: What is the Evidence?
– Case Presentation
– Robert Harrington, MD
Christopher P. Cannon, MD
Disclosures
Grants/Research Support:
Accumetrics; AstraZeneca
Pharmaceuticals; GlaxoSmithKline;
Merck & Co., Inc.; Merck & Co.,
Inc./Schering-Plough Corporation
partnership; sanofi-aventis/Bristol-
Myers Squibb partnership; Schering-
Plough Corporation
7

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Welcome/Introduction and Interactive Case Presentation #1
2007 ACC/AHA UA/NSTEMI
Guideline Revision
ACS Risk Stratification
1. Integral prerequisite to decision making
a) Intensive initial assessment
b) Continuous clinical assessment
c) Targeted ECG and marker data
2. Risk based on contingent probabilities
a) Probability of obstructive CAD causing ischemia
b) Risk given presence of obstructive CAD
3. Risk scores should be a routine part of
assessment throughout the hospital course and
periodically after discharge
Anderson JL, et al. J Am Coll Cardiol 2007;50:652-726.
Risk Assessment Dependent
on Contingent Probabilities
Likelihood of
obstructive CAD as
cause of symptoms
– Dominated by acute
findings
– Exam
– Symptoms
– Markers
– Traditional risk factors
are of limited utility
Does this patient have
symptoms due to
acute ischemia from
obstructive CAD?
Anderson JL, et al. J Am Coll Cardiol 2007;50:652-726.
Risk of bad
outcome
– Dominated by
acute findings
– Older age very
important
– Hemodynamic
abnormalities
critical
– ECG, markers
What is the
likelihood of death,
MI, heart failure?
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8

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Welcome/Introduction and Interactive Case Presentation #1
Overview: Likelihood of ACS
Secondary to CAD
Feature
History
Examination
ECG
Cardiac
Markers
High
Likelihood
Any below:
Typical angina
Known hx of
CAD,
including MI
CHF
New ECG Δs
⊕
Intermediate
Likelihood
No high-likelihood
features but any below:
Probable angina
Age > 70 years
Male, DM
PVD, CVA
Old ECG
abnormalities
Normal
Low Likelihood
No high- or
intermediate-likelihood
features but may have:
Atypical symptoms
Pain on palpation
Normal ECG
Normal
Anderson JL, et al. J Am Coll Cardiol 2007;50:652-726.
TIMI Risk Score For UA/NSTEMI
7 Independent Predictors
1. Age ≥ 65 years
2. ≥ 3 CAD Risk Factors
(↑ chol, FHx, HTN, DM, smoking)
3. Prior CAD (cath stenosis > 50%)
4. ASA in last 7 days
5. ≥ 2 Anginal events ≤ 24 hours
6. ST deviation
7. Elevated Cardiac Markers
(CK-MB or Troponin)
Antman EM, et al. JAMA 2000;284:835-842.
http://www.timi.org.
Relationship of TIMI Risk Score
to Morbidity and Mortality
TIMI
Risk Score
0-1
2
3
4
5
6-7
All-Cause Mortality, New or Recurrent MI,
or Severe Recurrent Ischemia Requiring
Urgent Revascularization Through 14 Days
After Randomization, %
4.7
8.3
13.2
19.9
26.2
40.9
Antman EM, et al. JAMA 2000;284:835-842.
9

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Welcome/Introduction and Interactive Case Presentation #1
Risk Scores
History
Presentation
TIMI
Age
Hypertension
Diabetes
Smoking
Cholesterol
Family history
History of CAD
Severe angina
Aspirin within 7 days
Elevated markers
ST segment
deviation
GRACE
Age
Heart rate
Systolic BP
Elevated markers
Heart failure
Cardiac arrest
Elevated markers
ST segment deviation
Anderson JL, et al. J Am Coll Cardiol 2007;50:652-726.
Future
Continuous
assessment
New markers
Electronic health
records
GRACE Risk Stratification
Age (years)
History CHF
History MI
HR
SBP
Points
(Range)
0-100
24
12
0-43
0-24
ST-segment
depression
BL creatinine
Elevated cardiac
enzymes
No In-hospital
PCI
Points
(Range)
11
1-20
15
14
Granger CB, et al. Arch Intern Med 2003;163:2345-2353.
Biomarkers of ACS
Established and Potential Biomarkers of ACS
American College of Cardiology Foundation.
0

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Welcome/Introduction and Interactive Case Presentation #1
Relative Risk of Cardiac Morbidity
as a Function of Number of
Elevated Biomarkers at 10 Months
Relative
Risk
Multimarkers for Predicting Individual Endpoints
at 10 Months: OPUS-TIMI 16
10
8
6
4
2
0
* p-value for trend
Number of elevated cardiac biomarkers
0 1 2 3
p = .0001* p = .004* p = .0009*
8.5
5.1
3.9
3.9
2.3 2.0 2.3
1.0 0.9
1.0 1.0
1.8
Death Myocardial Infarction Congestive Heart
Failure
Sabatine MS, et al. Circulation 2002;105:1760-1763.
Choosing a Strategy
Based on Risk
Preferred Strategy
Invasive
Patient Characteristics
Recurrent angina or ischemia at rest of with low-level activities
despite intensive medical therapy
Elevated cardiac biomarkers (TnT of TnI)
New or presumably new ST-segment depression
Signs or symptoms of HF or new or worsening mitral
regurgitation
High-risk findings from noninvasive testing
Hemodynamic instability
Sustained ventricular tachycardia
PCI within 6 months
Prior CABG
High-risk score (e.g., TIMI, GRACE)
Reduced LV function (LVEF less than 40%)
Conservative
Low-risk score (e.g., TIMI, GRACE)
Patient or physician preference in absence of high-risk features
Anderson JL, et al. J Am Coll Cardiol 2007;50:652-726.
2007 ACC/AHA UA/NSTEMI
Guideline Revision
Selection of Strategy: Invasive Versus
Conservative Strategy
In initially stabilized patients, an initially
conservative (i.e., a selectively invasive) strategy
may be considered in patients (without serious
comorbidities or contraindications to such
procedures) who have an elevated risk for clinical
events, including those who are troponin-positive
(IIb, B). The decision to implement an initial
conservative strategy may consider physician and
patient preferences (IIb, C)
A conservative strategy is recommended in
women with low-risk features (I, B)
Anderson JL, et al. J Am Coll Cardiol 2007;50:652-726.

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Welcome/Introduction and Interactive Case Presentation #1
Relative Risk for All-Cause Mortality
Early Invasive vs. Conservative Therapy
Study
FRISC-II
TRUCS
TIMI-18
VINO
RITA-3
ISAR-COOL
ICTUS
Overall RR (95% CI)
0.75 (0.63-0.90)
0.1 1 10
Favors
Early Invasive
Therapy
Invasive
Bavry A, et al. J Am Coll Cardiol 2006;48:1319-1325.
45
3
37
2
102
0
15
Favors
Conservative
Therapy
Deaths, n
Conservative
67
9
39
9
132
3
15
Follow-Up,
Months
24
12
6
6
60
1
12
(%)
30
25
20
15
10
5
Benefit of Invasive Strategy
by Troponin and ST Δ’s
Death, MI, Rehosp ACS at 6 Months
CONS
p = NS
16.9
14.5
INV
24.2 p < .001
*
14.8
0
0
TnT - TnT +
No ST chg
Morrow DA, et al. JAMA 2001;286:2405-2412.
Cannon CP, et al. N Engl J Med 2001;344:1879-1887.
30
25
20
15
10
5
26.3 p < .001
p = NS
*
15.3 15.6 16.4
ST chg
Case Presentation
53-year-old man
– Previous history of NSTEMI
– 1 year earlier: treated with 1 DES in RCA, mild disease
in LAD and LCx
Currently presents with chest discomfort at rest
lasting 20 mins – and improved with 2 sl nitro
Current medications
– Aspirin 81 mg QD
– Metoprolol 100 mg bid
– Simvastatin 40 mg QHS
– Ramipril 10 mg QD
NSTEMI = non-ST-elevation myocardial infarction; BMS = bare metal stent;
PTCA = percutaneous transluminal coronary angioplasty

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Welcome/Introduction and Interactive Case Presentation #1
Case Presentation (cont’d.)
Patient’s medical history
– Dyslipidemia
– HTN x 10 years
– Smoking x 10 years
– Borderline glucose intolerance (but not DM)
– No FHx CAD
ECG: normal sinus rhythm, lateral ST depression 1mm
Lab test result: Troponin I level < 0.03 ng/mL
Exam results
– Weight 210 pounds, height 5’10” (BMI 30.1)
– Blood pressure: 114/78 mm Hg
– Pulse: 74 beats per minute
– Lungs are clear to auscultation
– Cardiac: Normal S 1 S 2 , no S 3 or S 4 , no murmur
ECG = electrocardiogram; RRR = regular rate and rhythm
Case Presentation (cont’d.)
What is this patient’s risk
level?
1. High
2. Low
83%
17%
1 2
3

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Welcome/Introduction and Interactive Case Presentation #1
What strategy would you
follow for this patient?
1. Invasive
2. Conservative
84%
16%
1 2
If you were at a hospital without a
cath lab, would you still plan an
invasive strategy?
1. Yes – would transfer
the patient for cath
2. No – I would monitor
the patient for
recurrent symptoms
and transfer only for
recurrent pain
3. No – I would manage
conservatively
66%
33%
1%
1 2 3
4

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
BIBLIOGRAPHY
American College of Cardiology Foundation. www.acc.org.
Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients
with unstable angina/non-ST-elevation myocardial infarction. J Amer Coll Cardiol 2007;50:3-157.
Antman EM, Cohen M, Bernink PJL, et al. The TIMI risk score for unstable angina/non-ST elevation MI.
A method for prognostication and therapeutic decision making. JAMA 2000;284;835-842.
Bavry AA, Kumbhani DJ, Rassi AN, et al. Benefit of early invasive therapy in acute coronary syndromes: a
meta-analysis of contemporary randomized clinical trials. J Amer Coll Cardiol 2006;48:1319-1325.
Cannon CP, Weintraub WS, Demopoulos LA, et al. TACTICS (Treat Angina with Aggrastat and Determine
Cost of Therapy with an Invasive or Conservative Strategy)--Thrombolysis in Myocardial Infarction 18
Investigators. Comparison of early invasive and conservative strategies in patients with unstable coronary
syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001;344:1879-1887.
Granger CB, Goldberg RJ, Dabbous O, et al. Predictors of hospital mortality in the global registry of acute
coronary events. Arch Int Med 2003;163:2345-2353.
Jaffe AS, Babuin L, Apple FS. Biomarkers in acute cardiac disease: the present and the future. J Amer Coll
Cardiol 2006;48:1-11.
Morrow DA, Cannon CP, Nader R, et al. Ability of minor elevations of troponins I and T to predict benefit
from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction.
JAMA 2001;286:2405-2412.
Sabatine MS, Morrow DA, de Lemos, JA, et al. Multimarker approach to risk stratification in non-ST
elevation acute coronary syndromes. Simultaneous assessment of troponin I, c-reactive protein, and
B-type natriuretic peptide. Circulation 2002;105:1760-1763.
25

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
Treatment Guidelines:
Evidence and Application
Jeffrey L. Anderson, MD, FACC,
FAHA, MACP
Intermountain Medical Center
University of Utah
Jeffrey L. Anderson, MD, FACC,
FAHA, MACP
Disclosures
Research Support:
AstraZeneca Pharmaceuticals
Speakers Bureau: Merck & Co., Inc.
Consultant:
Eli Lilly and Company/CSI
Honorarium:
Schering-Plough Corporation
Antithrombotic Rx for ACS
Initial Conservative Strategy
Diagnosis of UA/NSTEMI is Likely or Definite
ASA (Class I, LOE: A)
Clopidogrel if ASA intolerant (Class I, LOE: A)
Select Management Strategy
Proceed with
Invasive Strategy
Conservative Strategy
Initiate A/C Rx (Class I, LOE: A):
Acceptable options: enoxaparin or UFH (Class I, LOE: A) or fondaparinux
(Class I, LOE: B), but enoxaparin or fondaparinux are preferable (Class IIA, LOE: B)
Initiate clopidogrel (Class I, LOE: A)
Consider adding IV eptifibatide or tirofiban (Class IIb, LOE: B)
(Risk stratification)
Anderson JL, et al. J Am Coll Cardiol 2007;50:652-726.
26

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
Antithrombotic Rx for ACS
Initial Invasive Strategy
Diagnosis of UA/NSTEMI is Likely or Definite
ASA (Class I, LOE: A)
Clopidogrel if ASA intolerant (Class I, LOE: A)
Select Management Strategy
Proceed with an
Initial Conservative
Strategy
Invasive Strategy
Initiate A/C Rx (Class I, LOE: A)
Acceptable options: enoxaparin or UFH (Class I, LOE: A) bivalirudin or fondaparinux (Class I, LOE: B)
Prior to Angiography
Initiate at least one (Class I, LOE: A) or both (Class IIa, LOE: B) of the following:
Clopidogrel, IV GP IIb/IIIa inhibitor
Factors favoring admin of both clopidogrel and GP IIb/IIIa inhibitor include:
Delay to Angiography, High Risk Features, Early recurrent ischemic discomfort
Proceed to Diagnostic Angiography
Anderson JL, et al. J Am Coll Cardiol 2007;50:652-726.
Antithrombotic Therapy for ACS
What Are the Choices?
Anticoagulants
–Unfractionated heparin
–Low molecular weight heparin
–Bivalirudin
–Fondaparinux
Antiplatelet Agents
–Aspirin
–Clopidogrel (P2Y12 inhibitors)
–GP IIb/IIIa inhibitors
Anderson JL, et al. J Am Coll Cardiol 2007;50:652-726.
Anticoagulants
27

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
Enoxaparin (LMWH) vs.
Heparin in ACS
Percent
12
10
8
6
4
2
OR 0.91
(0.83-0.99)
11
10.1
0
D/MI 30d
* 6 trials; N = 21,946 pts
Petersen JL, et al. JAMA 2004;292:89-96.
3.9
OR 1.1
(0.96-1.3)
3.7
Major Bleed
Enox
UFH
SYNERGY: Enoxaparin vs. UFH
with an Early Invasive Strategy
Freedom from Death / MI
1.0
0.95
0.9
0.85
Enoxaparin
UFH
0.8
0 5 10 15 20 25 30
Days from Randomization
Ferguson JJ, et al. JAMA 2004;292:45-54.
Hazard Ratio (95% CI)
30-Day Death/MI
HR 0.96
(0.87-1.06)
1.1
0.8 1 1.2
Enoxaparin UFH
Better Better
ACUITY: Bivalirudin for ACS
with an Invasive Strategy
% 30 d Events
14
12
10
8
6
4
2
0
UFH/Enox + GPI Bival + GPI
11.7 11.8
7.3 7.7
5.7 5.3
Net Clinical Outcome Ischemic Composite Major Bleeding
Outcomes non-inferior (p < .01) but not superior for Bival + GPI
Stone GW, et al. N Engl J Med 2006;355:2203-2216.
28

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
OASIS-5: Fondaparinux*
vs. LMWH for ACS
Death/MI/RI
Enox
5.8%
Fonda
5.9%
Hazard Ratio
Non-Inferiority
Margin = 1.185
Death/MI
4.1%
4.1%
Death
1.9%
1.8%
MI
2.7%
2.7%
Refract Isch
1.9%
2.05%
0.8 1 1.2
* 2.5 mg SC qd; N = 20,078; 9d 1° EP Fonda Better Enox Better
Yusuf S, et al. N Engl J Med 2006;354:1464-1476.
OASIS-6: Poor Efficacy of
Fondaparinux with Primary
PCI
N
Overall 12092
Initial Reperfusion Rx
None 2867
Thrombolytic 5436
Primary PCI 3789
GRACE Risk Score
< 112 5958
≥ 112 6134
UFH/
Placebo
11.2%
15.1
13.6
4.9
4.3
18.0
Fonda
9.7%
12.2
10.9
6.0
4.6
14.5
Hazard Ratio
Interaction
p-value
.04
.03
Turpie AGG. Vasc Health Risk Manag 2006;2:371-378.
0.5 0.8 1 1.2 1.6 2.0
Fonda Better UFH/PBO Better
Antiplatelet Agents
29

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
CURE: Oral Thienopyridine
Therapy for NSTE-ACS
Cumulative Hazard Rate
0.14
0.12
0.10
0.08
0.06
0.04
0.02
Placebo
+ ASA*
Clopidogrel
+ ASA*
0.00
0 3 6 9 12
Months of Follow-Up
* In addition to other standard therapies
p = .00009; N = 12,562
The CURE Trial Investigators. N Engl J Med 2001;345:494-502.
20%
Overall
Relative Risk
Reduction
GP IIb/IIIa Inhibition for ACS
Impact on 30 Day Death/MI
by Strategy
15%
10%
5%
0%
PRISM PLUS
Heparin
Tirofiban + Heparin
10.2% 10.1%
5.9%
42%↓ 23%↓
PCI < 72º
(n = 287)
7.8%
No Early PCI
(n = 1283)
20%
15%
10%
5%
0%
PCI < 72º
(n = 1228)
PURSUIT
Heparin
Eptifibatide + Heparin
16.7%
15.6%
14.5%
11.6%
31%↓ 6%↓
Morrow DA, et al. Am J Cardiol 2004;94:774-776.
The PURSUIT Trial Investigators. N Eng J Med 1998;339:436-443.
No Early PCI
(n = 8233)
Controversies in Dosing and
Timing
Aspirin dose with clopidogrel
– 162-325 mg/day for 1-6 mo after stenting (I-B)
– 75-162 mg/day for bleeding risk (II-C)
Clopidogrel loading dose
– 300 mg best studied
– 600 mg: platelet inhibition, efficacy (?)
Timing of clopidogrel vs. cath
– Pre-cath: efficacy, even with GPI (?)
– Post-cath: bleeding risk if surgery; GPI alone effective (?)
Use of GPI
– Best established as PCI adjunct for NSTEMI
– Benefit small with conservative strategy only
– Clopidogrel plus anticoagulant effective for UA/SA
30

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
Bleeding Complications in ACS
Bleeding is the most important non-ischemic
complication of ACS and its treatment, with
important prognostic implications
Frequency of major bleeding: 2% - 8%
GRACE Registry:
– STEMI: 3.9%
– NSTEMI: 4.7%
– UA: 2.3%
CRUSADE Registry: Transfusions in > 15%
Predictors of bleeding/death: age, female gender,
renal dysfunction
Moscucci M, et al. Eur Heart J 2003;24:1815-1823.
Impact of Bleeding on
Cardiovascular Risk
GRACE Registry (Hospital Death):
– HR 1.64 (1.18 - 2.28), p < .001
Meta-analysis (> 30,000 pts)
– 4 X -Death (30 d)
– 5 X -MI
– 3 X -Stroke
Pooled Multicenter Trials (26,452 pt)
– Mild HR = 1.6 (1 mo Death)
– Moderate HR = 2.7
– Severe HR = 10.6
Boersma E, et al. Lancet 2002;359:189-198.
Rao S, et al. Am J Cardiol 2005;96:1200-1206.
CURE: Major Bleeding by
Doses of ASA & Clopidogrel
ASA Dose
Placebo
+ ASA*
(N = 6303)
Clopidogrel
+ ASA*
(N = 6259)
p-value
< 100 mg
(N = 1927)
1.9%
3.0%
.53
100-200 mg
(N = 7428)
2.8%
3.4%
--
> 200 mg
(N = 2301)
3.7%
4.9%
--
* In addition to other standard therapies
Peters RJ, et al. Circulation 2003;108:1682-1687.
31

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
Clopidogrel Loading Dose
600 mg vs. 300 mg
Trial
Ref
Circ 05;
SA or
4/12
ARMYDA-2 1
255
--
111:2099
ACS
(p = .04)
ISAR- Circ 05;
47/33 (5)*
40 SA
--
Choice 2 112:2946
30/15 (20)*
JACC 06;
39/22 (5)*
ALBION 3 69 ACS
6/11
48:931
29/18 (20)*
JACC 06;
5/18
Cuisset 4 292 ACS 50/39 (10)
48:1339
(p = .02)
* Inhibition of Platelet Activity (IPA) at 4 h with 5 or 20 µmol/L ADP
600/300 IPA comparisons all significant
N
Pop
% IPA
600/300
% MACE
References available in the supplemental bibliography section of course guide.
OASIS-5: Fondaparinux vs.
LMWH and Bleeding Risk
Cumulative Hazard
0.05
0.04
0.03
0.02
0.01
Enoxaparin
Fondaparinux
0
0 3 6 9 12 15 18 21 24 27 30
HR 0.63; 95% CI 0.55-0.73; p < .00001
Days
Yusuf S, et al. N Engl J Med 2006;354:1464-1476.
Cumulative Hazard
0.07
0.06
0.05
0.04
0.03
0.02
0.01
OASIS-5: Mortality at
6 Months
Enoxaparin
Yusuf S, et al. N Engl J Med 2006;354:1464-1476.
Fondaparinux
0
0 20 40 60 100 120 140 160 180
HR 0.89; 95% CI 0.79-0.99; p = .037
Days
32

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
ACUITY: Reduced Bleeding
With Bivalirudin Without a GPI
% 30 d Events
14
12
10
8
6
4
2
0
11.7
*
10.7
Net Clinical
Outcome
UFH/Enox + GPI
7.3
7.8
Ischemic Composite
Bival
5.7
*
3
Major Bleeding
Stone GW, et al. N Engl J Med 2006;355:2203-2216.
Balance of Efficacy
and Safety
Endpoint (%)
15
10
5
Clopidogrel Prasugrel
CV Death/MI/Stroke
TIMI Major NonCABG Bleeds
12.1
9.9
2.4
1.8
0 30 60 90 180 270 360 450
Days
Wiviott SD, et al. N Engl J Med 2007;357:2001-2015.
138 Events
HR .81
(.73 - .90)
p = .0004
NNT = 46
35 Events
HR 1.32
(1.03 - 1.68)
p = .03
NNT = 167
Bleeding Risk
Subgroups
Therapeutic Considerations
Significant Net Clinical
Benefit with Prasugrel
Reduced MD
Guided by PK
Age ≥ 75 or Wt < 60 kg
16%
4%
Avoid Prasugrel
Prior CVA/TIA
80%
MD
10 mg
Wiviott SD, et al. N Engl J Med 2007;357:2001-2015.
33

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
Applying the Evidence
Patient with UA, with ST changes.
What anticoagulant would you start
in the ED?
1. Unfractionated
heparin
2. Enoxaparin
3. Fondaparinux
4. Bivalirudin
36%
45%
10%
10%
1 2 3 4
For clopidogrel, what would
you recommend in the ED?
1. Clopidogrel 600 mg
2. Clopidogrel 300 mg
3. No clopidogrel in ED, but
600 mg post cath
4. No clopidogrel in ED, but
300 mg post cath
28%
33%
27%
12%
1 2 3 4
34

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
For GP IIb/IIIa inhibition,
what would you recommend?
1. Small molecule
GP IIb/IIIa in the
ED
2. GP IIb/IIIa
inhibitor only for
PCI
3. No GP IIb/IIIa
inhibitor
42%
38%
20%
1 2 3
Case Presentation (cont’d.)
53-year-old man
– UA and ST segment changes
– Troponin negative
Current medications
– ASA, clopidogrel 600 mg, UFH
– Eptifibatide
Cath arranged later that day
LAD
Lesion
Left
Main
LCx
lesion
Circumflex
Courtesy of Gibson CM.
35

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
Treatment Guidelines: Evidence and Application
Case Presentation (cont’d.)
Patient had successful 2 vessel
stenting with DES in LAD and LCx
Patient was admitted and observed
overnight
36

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
BIBLIOGRAPHY
Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients
with unstable angina/non-ST-elevation myocardial infarction. J Amer Coll Cardiol 2007;50:3-157.
Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary
syndromes: a meta-analysis of all major randomized trials. Lancet 2002;359:189-198.
Cuisset T, Frere C, Quilici J, et al. Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity
and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing
coronary stenting. J Amer Coll Cardiol 2006;48:1339-1345.
Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with
non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy.
Primary results of the SYNERGY randomized trial. JAMA 2004;292:45-54.
Montalescot G, Sideris G, Meulman C, et al. A randomized comparison of high clopidogrel loading doses
in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of the Best
Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) Trial. J Amer
Coll Cardiol 2006;48:931-938.
Morrow DA, Sabatine MS, Antman EM, et al. Usefulness of tirofiban among patients treated without
percutaneous coronary intervention (TIMI high risk patients in PRISM-PLUS). Am J Cardiol 2004;94:774-
776.
Moscucci M, Fox KAA, Cannon CP, et al. Predictors of major bleeding in acute coronary syndromes: the
Global Registry of Acute Coronary Events (GRACE). Eur Heart J 2004:24:1815-1823.
Patti G, Colonna G, Pasceri V, et al. Randomized trial of high loading dose of clopidogrel for reduction
of periprocedural myocardial infarction in patients undergoing coronary intervention: results from
the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty study).
Circulation 2005;111:2099-2106.
Peters RJG, Mehta SR, Fox KAA, et al. Effects of aspirin dose when used alone or in combination with
clopidogrel in patients with acute coronary syndromes. Observations from the clopidogrel in unstable
angina to prevent recurrent events (CURE) study. Circulation 2003;108:1682-1687.
Petersen JL, Mahaffey KW, Hasselblad V, et al. Efficacy and bleeding complications among patients
randomized to enoxaparin or unfractionated heparin for antithrombin therapy in non-ST-segment elevation
acute coronary syndromes. A systematic overview. JAMA 2004;292:89-96.
Rao SV, O’Grady K, Pieper KS, et al. Impact of bleeding severity on clinical outcomes among patients with
acute coronary syndromes. Am J Cardiol 2005;96:1200-1206.
Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Eng J
Med 2006;355:2203-2216.
37

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
The CURE Trial investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary
syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502.
The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with
acute coronary syndromes. Platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using
integrilin therapy. N Engl J Med 1998;339:436-443.
Turpie AGG. Fondaparinux in the management of patients with ST-elevation acute myocardial infarction.
Vasc Health Risk Manag 2006;2:371-378.
Wiviott SD, Braunwald E, McCable CH, et al. Prasugrel versus clopidogrel in patients with acute coronary
syndromes. N Eng J Med 2007;357:2001-2015.
von Beckerath N, Taubert D, Pogatsa-Murray G, et al. Absorption, metabolization, and antiplatelet effects
of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary
Stenting and Antithrombotic Regimen: Choice Between 3 High Oral Doses for Immediate Clopidogrel
Effect) trial. Circulation 2005;112:2946-2950.
Yusuf, S, Mehta SR, Chrolavicius S, et al. Comparison of fondaparinux and enoxaparin in acute coronary
syndromes. N Eng J Med 2006;1464-1476.
38

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
SUPPLEMENTAL BIBLIOGRAPHY
Slide Title: Clopidogrel Loading Dose—600 mg vs. 300 mg
1. Patti G, Colonna G, Pasceri V, et al. Randomized trial of high loading dose of clopidogrel for reduction
of periprocedural myocardial infarction in patients undergoing coronary intervention: results from
the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty study).
Circulation 2005;111:2099-2106.
2. von Beckerath N, Taubert D, Pogatsa-Murray G, et al. Absorption, metabolization, and antiplatelet
effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE
(Intracoronary Stenting and Antithrombotic Regimen: Choice Between 3 High Oral Doses for Immediate
Clopidogrel Effect) trial. Circulation 2005;112:2946-2950.
3. Montalescot G, Sideris G, Meulman C, et al. A randomized comparison of high clopidogrel loading
doses in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of
the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis)
Trial. J Amer Coll Cardiol 2006;48:931-938.
4. Cuisset T, Frere C, Quilici J, et al. Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity
and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing
coronary stenting. J Amer Coll Cardiol 2006;48:1339-1345.
39

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
New Discoveries in Prevention and Management: What Is the Evidence?
New Discoveries in
Prevention and Management:
What Is the Evidence?
Robert A. Harrington, MD
Duke University Medical Center
Duke Clinical Research Institute
Robert A. Harrington, MD
Disclosures
Duke Clinical Research Institute-DCRI Grants: Abbott Vasc-
Devices; Acorn Cardiovascular; Actelion; Acusphere, Inc.; Adolor
Corporation; Advanced CV Systems; Advanced Stent Technologies,
Inc.; Agilent Technologies, Inc.; Ajinomoto Co., Inc.; Alsius
Corporation; Allergan, Inc.; Amgen Inc.; Amylin Pharmaceuticals Inc.;
Anadys Pharmaceuticals, Inc.; ANGES MG, Inc.; Arginox
Pharmaceuticals, Inc.; Angiometrx Inc.; Ark Therapeutics Group plc;
Astellas Pharma US, Inc.; Astra Hassle; AstraZeneca
Pharmaceuticals; Atritech, Inc.; Aventis; Avion Flumist; Baxter; Bayer
AG; Bayer Corporation; Berlex Laboratories; Biogen Idec; Bioheart,
Inc.; Biosense Webster, Inc.; Biosite, Inc.; Bio-Technology General;
Boehringer-Ingelheim Pharmaceuticals, Inc.; Boston MedTech
Advisors; Boston Scientific Corporation; Bristol-Myers Squibb
Company; CanAm Bioresearch Inc.; Cardiac Science, Inc.;
CardioThoracic Systems, Inc.; CardioDynamics International;
CardioKinetix Inc.; Celsion Corporation; Centocor, Inc.; Cerexa, Inc.;
Chugai Pharma USA, LLC; Cierra, Inc.; Coley Pharma Group;
Robert A. Harrington, MD
Disclosures
DCRI Grants Cont.: Conor Medsystems, LLC.; Corautus Genetics,
Inc.; Cordis Corporation; Corgentech; Covalent Group; Critical
Therapeutics, Inc.; Cubist Pharmaceuticals; CV Therapeutics, Inc.;
Cytokinetics, Inc.; Dade Behring; Daiichi; deCODE Genetics; Dyax
Corp.; Echosens, Inc.; Eclipse Surgical Technologies; Edwards
Lifesciences; Eisai Pharmaceuticals; Eli Lilly and Company; Enzon
Pharmaceutical; EPI-Q, Inc.; ev3, Inc.; Evalve, Inc.; First Circle
Medical, Inc.; First Horizon; Flow Cardia, Inc.; Fox Hollow
Pharmaceutical; Fujisawa; Genentech, Inc.; General Electric
Healthcare; General Electric Medical Systems; Genzyme Corporation;
Getz Bros, Co., Inc.; Gilead Sciences, Inc.; GlaxoSmithKline; Guidant;
Guilford Pharmaceuticals; Heartscape Technologies, Inc.; Hoffmann-
La Roche Inc.; Human Genome Sciences; Humana; iCo Therapeutics
Inc.; IDB Medical; Idenix Pharmaceuticals, Inc.; Idera
Pharmaceuticals, Inc.; Idun Pharmaceuticals, Inc.; Immunex;
INFORMD, Inc.; InfraReDx, Inc.; Inhibitex, Inc.; Innocoll
Pharmaceuticals; INO Therapeutics, Inc.;
40

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
New Discoveries in Prevention and Management: What Is the Evidence?
Robert A. Harrington, MD
Disclosures
DCRI Grants Cont.: Inspire Pharmaceuticals, Inc.; Intarcia
Therapeutics, Inc.; Integrated Therapeutics Group; InterMune
Pharmaceuticals; Inverness Medical Innovations; Ischemix, Inc.; ISIS
Pharmaceuticals, Inc.; Johnson & Johnson; Jomed, Inc.; KAI
Pharmaceuticals; Kerberos Proximal Inc.; King Pharmaceuticals, Inc.;
Kuhera Chemical Co.; Lumen Biomedical; Meacoustics; Medicure
Inc.; Medicure MiniMed; Medi-Flex, Inc.; MedImmune, Inc.; Medtronic,
Inc.; Merck Co., & Inc.; MicroMed Tech, Inc.; Microphage, Inc.;
Millennium Pharmaceutical; Mitsubishi; Momenta Pharmaceuticals,
Inc.; Mycosol, Inc.; NABI Biopharmaceuticals; Neuron
Pharmaceuticals, Inc.; NitroMed, Inc.; NovaCardia, Inc.; Novartis
Pharmaceuticals Corporation; Organon International; Ortho Biotech
Products, LP; OSI Eyetech; Osiris Therapeutics, Inc.; Otsuka America
Pharmaceutical, Inc.; Pathway Medical Technologies, Inc.; PDL
BioPharma, Inc.; Pfizer Inc.; Pharmanetics, Inc.; Pharmassest, Inc.;
Pharsight Corporation; Portola Pharmaceuticals, Inc.; Proctor &
Gamble; Prometheus Laboratories Inc.; Purdue Pharma LP;
Robert A. Harrington, MD
Disclosures
DCRI Grants Cont.: Radiant Pharma; Recom Managed Systems;
Regado Biosciences, Inc.; Reliant Pharmaceuticals, LLC; Roche
Diagnostic Corp.; Roche Labs; Salix Pharmaceuticals; sanofi-pasteur;
sanofi-aventis; sanofi-synthelabo; Schering-Plough Corporation;
SciClone Pharmaceuticals, Inc.; Scios Inc.; Searle Pharmaceutical
Products; Sicel Technologies, Inc.; Siemens; Social Scientific
Systems, Inc.; Spectranetics Corporation; Summit Pharmaceuticals
International Corporation; Sunesis Pharmaceuticals, Inc.; TAP
Pharmaceutical Products Inc.; Terumo Corporation; The Medicines
Company; Theravance, Inc.; TherOx, Inc.; Thoratec Corporation;
Titan Pharmaceuticals, Inc.; United Therapeutics; Uptake Medical
Corp.; Valeant Pharmaceuticals International; Valentis, Inc.; Vascular
Solutions, Inc.; Velocimed Inc.; Veridex, LLC; Vertex
Pharmaceuticals; Viasys Healthcare, Inc.; Vicuron Pharmaceuticals
Inc.; Wyeth Pharmaceuticals; Wyeth-Ayerst, XOMA LLC; Xsira
Pharmaceuticals, Inc.; XTL Biopharmaceuticals Ltd.; Yamanouchi
Pharma America, Inc.
Robert A. Harrington, MD
Disclosures
Individual Grants: Bristol-Myers Squibb
Company; KAI Pharmaceuticals; Medicure Inc.;
Millennium Pharmaceuticals; Inc.; Proctor &
Gamble; Schering-Plough Corporation
Research Support (DCRI): Bristol-Myers Squibb
Company; CanAm Bioresearch Inc.
Speakers Bureau: Schering-Plough Corporation
with honorarium for Duke
Consultant: AstraZeneca Pharmaceuticals;
Bristol-Myers Squibb Company; sanofi-aventis;
Schering-Plough Corporation; Seredigm; WebMD
41

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
New Discoveries in Prevention and Management: What Is the Evidence?
Lipid Management Goal
I IIa IIb III
LDL-C should be less than 100 mg/dL
I IIa IIb III
Further reduction to LDL-C to < 70 mg/dL
is reasonable
If TG > 200 mg/dL, non-HDL-C should be < 130 mg/dL*
* Non-HDL-C = total cholesterol minus HDL-C
Anderson JL, et al. J Am Coll Cardiol 2007;50:652-726.
Lipid Management
Pharmacotherapy
Therapy
TC
LDL
HDL
TG
Patient
Tolerability
Statins* 1-3
19-37%
25-50%
4-12%
14-29%
Good
Ezetimibe 4
13%
18%
1%
9%
Good
Bile acid
sequestrants 1-2
7-10%
10-18%
3%
Neutral or
Poor
Nicotinic acid 1-2
10-20%
10-20%
14-35%
30-70%
Reasonable
to Poor
Fibrates 1-2
19%
4-21%
11-13%
30%
Good
HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein
cholesterol; TC = total cholesterol; TG = triglycerides
* Daily dose of 40 mg of each drug, excluding rosuvastatin
References available in the supplemental bibliography section of course guide.
Proportional Effects on Major
Vascular Events per mmol/L LDL
Cholesterol Reduction
Effect p < .0001
Cholesterol Treatment Trial Collaborators. Lancet 2005;366:1267-1278.
42

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
New Discoveries in Prevention and Management: What Is the Evidence?
IMPROVE-IT
Amendment 2
Patients stabilized post Acute Coronary Syndrome < 10 days
LDL ≤ 125*mg/dL (or ≤ 100**mg/dL if prior lipid-lowering Rx)
Double-blind ASA + Standard Medical Therapy
N = 12,500
Simvastatin 40 mg
Eze/Simva 10/40 mg
Follow-Up Visit Day 30, Every 4 Months
* 3.2mM; ** 2.6mM
Duration: Minimum 2 1/2 year follow-up (> 5250 events)
Primary Endpoint: CV Death, MI, Hospital Admission for UA,
revascularization (> 30 days after randomization), or Stroke
ClinicalTrials.gov Identifier: P04103.
OASIS-7 Study Design
Patients with UA/NSTEMI planned for early invasive
strategy, i.e., intend for PCI as early as possible within 24 hrs
RANDOMIZE
Clopidogrel High-Dose Group
Clopidogrel 600 mg loading dose Day 1 followed
by 150 mg from Day 2 to 7;
75 mg from Day 8 to 30
RANDOMIZE
Clopidogrel Standard-Dose Group
Clopidogrel 300 mg (+ placebo) Day 1 followed
by 75 mg (+ placebo) from Day 2 to 7;
75 mg from Day 8 to 30
RANDOMIZE
ASA low-dose group
At least 300 mg Day 1;
75-100 mg
from Day 2 to 30
ASA high-dose group
At least 300 mg Day 1;
300-325 mg
from Day 2 to 30
ASA low-dose group
At least 300 mg Day 1;
75-100 mg
from Day 2 to 30
ASA high-dose group
At least 300 mg Day 1;
300-325 mg
from Day 2 to 30
PCI = percutaneous coronary intervention;
UA/NSTEMI = unstable angina/non-ST-segment elevation myocardial infarction
Mehta SR. Eur Heart J 2006;8(Suppl G):G25-G30.
TRITON - TIMI38
Study Design
ACS (STEMI or UA/NSTEMI) & Planned PCI
ASA
Double-blind
N = 13,600
CLOPIDOGREL
300 mg LD/ 75 mg MD
PRASUGREL
60 mg LD/ 10 mg MD
Median duration of therapy - 12 months
1 o endpoint: CV death, MI, Stroke
2 o endpoints: CV death, MI, Stroke, Rehosp-Rec Isch
CV death, MI, UTVR Stent Thrombosis (ARC definite/prob.)
Safety endpoints: TIMI major bleeds, Life-threatening bleeds
Key Substudies: Pharmacokinetic, Genomic
Wiviott SD, et al. Am Heart J 2006;152:627-635.
43

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
New Discoveries in Prevention and Management: What Is the Evidence?
Timing of Benefit
Landmark Analysis
8
Clopidogrel
Prasugrel
6.9
Primary Endpoint (%)
6
4
2
HR .82
p = .01
5.6
4.7
0
0 1 2 3 30 60 90 180 270 360 450
Loading Dose
Days
Triton-TIMI 38 presented at AHA 2007.
HR .80
p = .003
Maintenance Dose
5.6
ISAR REACT-2: Is Clopidogrel*
Alone Sufficient Without GPI
in NSTEMI?
Composite of death, MI, or urgent TVR due to
Myocardial Ischemia within 30 days (%)
15%
10%
5%
0%
8.9%
Abciximab
11.9%
Placebo
The primary
composite
endpoint occurred
less frequently in
the abciximab
group compared
to placebo (8.9%
vs. 11.9%; relative
risk [RR] 0.75;
p = .03)
* 600 mg load > 2h pre-PCI; N = 2022 pts; p = .03
Kastrati A, et al. JAMA 2006;295:1531-1538.
PLATO Study Design
Patients: ACS, Moderate-High Risk UA/NSTEMI/STEMI
PCI, Medically Managed, or CABG
All Receiving ASA Clopidogrel Treated or Naïve
Clopidogrel
If pretreated, no additional load;
if naïve, standard 300 mg load,
then 75 mg/day maintenance;
additional 300 mg permitted pre-PCI
AZD6140
180 mg load, then
90mg/d maintenance;
additional 90 mg pre-PCI
12 month maximum exposure (Min = 6 mo, max = 12 mo, mean = 11 mo)
Primary Endpoint: CVD/MI/stroke
Secondary EP: CVD/MI/Stroke/Revascularization with PCI;
CVD/MI/Stroke, Severe recurrent ischemia
N = 18,000 pts
ClinicalTrials.gov Identifier: NCT00391872.
44

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
New Discoveries in Prevention and Management: What Is the Evidence?
TRA-PCI Study
Design
Non-Urgent PCI or Cath possible PCI (All Receive Aspirin)
Randomization #1 — 3:1 SCH530348:Placebo (Single Loading Dose)
Sequential Groups: 1 = 10 mg; 2 = 20 mg; 3 = 40 mg, or Placebo
Cardiac Catheterization
Planned PCI (All Receive Clopidogrel and Antithrombin)
No PCI**
Randomization #2 1:1:1
Maintenance Therapy Once Daily for ~ 60 days
SCH 530348 Loading Dose → SCH 530348
Or Placebo Loading Dose → Placebo
0.5 mg
n ~ 100
SCH 530348
1 mg
n ~ 100
2.5 mg
n ~ 100
Placebo
n ~ 100
CABG
Quantify Postoperative
Chest-Tube Drainage,
Transfusions, and
Re-exploration
Medical
Management
Safety: TIMI Major plus Minor Bleeding
Efficacy: Death/MACE
Safety: TIMI Major plus Minor
Bleeding
* Primary Evaluable Cohort ** Secondary Evaluable Cohort
Moliterno DJ, et al. Presented at ACC 2007.
Thrombin Receptor
Antagonism
TRA Program (29,500 pts)
NSTE ACS
10,000 pts
2º Prevention
19,500 pts
TRA Placebo TRA Placebo
F/U 1 yr minimum
•1 o EP: Composite of CV
death, MI, stroke, urgent
revascularization and
recurrent ischemia w/
rehospitalization
ClinicalTrials.gov Identifier: NCT00527943.
•1 o EP: Composite of CV
death, MI, stroke, and
urgent revascularization
ClinicalTrials.gov Identifier: NCT00526474.
Apixaban Phase 2 secondary
prevention in ACS APPRAISE-1
(CV185023)
Recent ACS patients
≤ 7 days and at least one risk factor
Treated for 6
months
Randomized,
double-blind
All receive ASA
(< 165 mg)
Clopidogrel use
per investigator
(stratified
randomization)
Apixaban
2.5 mg BID
Apixaban
2.5 mg BID
Apixaban
10 mg BID
Phase A
Placebo
Apixaban
10 mg QD
Interim analysis (DSMB review)
Phase B
Placebo
Apixaban
10 mg QD
Apixaban
20 mg QD
Ph A ~ 450 pts
Ph B ~ 1350 pts
Total ~ 1800 pts
Efficacy endpoint: prevention of major CV events (death, non fatal MI,
severe recurrent ischemia, & stroke)
Safety endpoint: major bleeding (ISTH)
ClinicalTrials.gov Identifier: NCT00313300.
45

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
New Discoveries in Prevention and Management: What Is the Evidence?
ATLAS TIMI-46
Overview of Stage 1 Design
Recent ACS patients
Stabilized 1-7 days post-index event
N ~ 1,350
MD decision to treat with clopidogrel
Aspirin 75-100 mg
NO
YES
STRATUM 1 STRATUM 2
* Dose Levels
5, 10, & 20 mg
PLACEBO
RIVA
QD
RIVA
BID
PLACEBO
RIVA
QD
RIVA
BID
3 dose levels*
3 dose levels*
3 dose levels*
3 dose levels*
Treat for 6 months
Primary endpoint: TIMI significant bleeding
ClinicalTrials.gov Identifier: NCT00526474.
Applying the Evidence
For statin therapy, what target
LDL would you recommend?
1. < 100 mg/dL
2. < 70 mg/dL
77%
3. No target, just
keep high-dose
statin
14%
9%
1 2 3
46

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
New Discoveries in Prevention and Management: What Is the Evidence?
What duration of clopidogrel do
you recommend post DES?
1. 6 months
2. 1 year
3. 2 years
4. Indefinitely
33%
47%
11%
9%
1 2 3 4
If prasugrel were available
would you use it in this patient?
1. Yes – at time of
ED presentation
2. Yes – post cath,
and pre-PCI
3. No
30%
42%
28%
1 2 3
If prasugrel were available would
you use it long-term in this patient?
1. Yes – for 15 months as
done in the TRITON-
TIMI 38 trial
2. Yes – for approximately
2 years
3. Yes for 3 months, then
clopidogrel 75 mg daily
4. Yes for 1 month, then
clopidogrel
5. No – would use
clopidogrel
32%
11%
15%
4%
38%
1 2 3 4 5
47

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
New Discoveries in Prevention and Management: What Is the Evidence?
Case Presentation (cont’d.)
Patient was discharged home
ASA 325 mg for 3 months, then 81 mg daily
Clopidogrel 75 mg qd
Atorvastatin 80 mg qd
Metoprolol 100 BID
Ramipril 10 mg daily
Questions and
Answers
48

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
BIBLIOGRAPHY
Alexander KP, Chen AY, Roe MT, et al. Excess dosing of antiplatelet and antithrombin agents in the
treatment of non-ST-segment elevation acute coronary syndromes. JAMA 2005;294:3108-3116.
Alexander KP, Roe MT, Chen AY, et al. Evolution in cardiovascular care for elderly patients with non-STsegment
elevation acute coronary syndromes: results from the CRUSADE National Quality Improvement
Initiative. J Amer Coll Cardiol 2005;46:1479-1487.
Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients
with unstable angina/non-ST-elevation myocardial infarction. J Amer Coll Cardiol 2007;50:3-157.
Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment:
prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet
2005;366:1267-1278.
de Araujo Goncalves P, Ferreira J, Aguiar C, et al. TIMI, PURSUIT, and GRACE risk scores: sustained
prognostic value and interaction with revascularization in NSTE-ACS. Eur Heart J 2005;26:865-872.
Gupta EK, Ito MK. Lovastatin and extended-release niacin combination product: the first drug combination
for the management of hyperlipidemia. Heart Dis 2002;4:124-137.
Kastrati A, Mehilli J, Neumann FJ, et al. Intracoronary stenting and antithrombotic: Regimen rapid early
action for coronary treatment (ISAR-REACT 2) trial investigators. Abciximab in patients with acute coronary
syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT
2 randomized trial. JAMA 2006;295:1531-1538.
Knopp RH. Drug treatment of lipid disorders. N Eng J Med 1999;341:498-511.
Mehta SR. Clopidogrel in non-ST-segment elevation acute coronary syndromes. Eur Heart J Suppl 2006;8:
G25-G30.
National Cholesterol Education Program. Circulation 1994;98:1333-1445.
Soiza RL, Leslie SJ, Williamson P, et al. Risk stratification in acute coronary syndromes--does the TIMI risk
score work in unselected cases? QJM 2006;99:81-87.
Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Eng J
Med 2006;355:2203-2216.
Tang EW, Wong CK, Herbison P. Global Registry of Acute Coronary Events (GRACE) hospital discharge
risk score accurately predicts long-term mortality post acute coronary syndrome. Am Heart J 2007;153:29-
35.
Wiviott SD, Antman EM, Gibson CM, et al. Evaluation of prasugrel compared with clopidogrel in patients
with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic
Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis in Myocardial Infarction 38
(TRITON-TIMI 38). Am Heart J 2006;152:627-635.
Yeshurun D, Gotto AM JR. Hyperlipidemia: perspectives in diagnosis and treatment. South Med J
1995:88:379-391.
Yusuf, S, Mehta SR, Chrolavicius S, et al. Comparison of fondaparinux and enoxaparin in acute coronary
syndromes. N Eng J Med 2006;354:1464-1476.
49

Using Evidence and Guidelines
to Individualize Care for ACS:
A Case-Based Presentation
SUPPLEMENTAL BIBLIOGRAPHY
Slide Title: Lipid Management Pharmacotherapy
1. Yeshurun D, Gotto AM JR. Hyperlipidemia: perspectives in diagnosis and treatment. South Med J
1995:88:379-391.
2. National Cholesterol Education Program. Circulation 1994;98:1333-1445.
3. Knopp RH. Drug treatment of lipid disorders. N Eng J Med 1999;341:498-511.
4. Gupta EK, Ito MK. Lovastatin and extended-release niacin combination product: the first drug
combination for the management of hyperlipidemia. Heart Dis 2002;4:124-137.
50