UA/NSTEMI Guidelines Audio-Webcast:

A Presentation & Discussion of Treatment Essentials

Based on the ACC/AHA Guidelines for the Management of Patients With Unstable

Angina/Non-ST-Elevation Myocardial Infarction: A Report of the ACC/AHA Task

Force on Practice Guidelines Writing Committee to Revise the 2002 Guidelines for the Management of Patients with Unstable

Angina/Non-ST-Elevation Myocardial Infarction. Presented by:

Jeffrey L. Anderson, MD, FACC, ModeratorElliott M. Antman, MD, FACCRobert M. Califf, MD, MACC

A. Michael Lincoff, MD, FACC

AstraZeneca

Bristol-Myers Squibb

Merck

Sanofi

ThromboVision

DisclosuresJeffrey L. Anderson, MD, FACC

DisclosuresElliott M. Antman, MD, FACC

Accumetrics Inotek Pharmaceuticals Corp.

Amgen, Inc. Integrated Therapeutics Corp.

AstraZeneca Merck

Bayer Healthcare LLC Millennium

Biosite Novartis Pharmaceuticals

Boehringer Mannheim The National Institutes of Health

Beckman Coulter, Inc. Nuvelo, Inc.

Bristol-Myers Squibb Ortho-Clinical Diagnostics, Inc.

Centocor Pfizer, Inc.

CV Therapeutics Roche Diagnostics GmbH

Dade Sanofi-Aventis Research Institute

Dendrion Sanofi-Synthelabo Recherche

Eli Lilly * Schering-Plough

Genentech Sunoz Molecular

GlaxoSmithKline The National Institutes of Health

Abbott Laboratories AstraZeneca Boston Scientific Corautus Genetics, Inc.

Abbott Vascular Devices Aventis Bracco Diagnostics Cordis

Acorn Cardiovascular Aviron Flu Mist Bristol-Myers Squibb Corgentech

Actelion Bayer AG CanAm Bioresearch, Inc. Covalent Group

Acushphere, Inc. Bayer Corp Cardiac Sciences, Inc. Critical Therapeutics, Inc.

Advanced CV Systems Berlex Cardiodynamics CryoVascular Systems, Inc.

Advanced Stent Tech Biocompatibles, Ltd CardioKinetix, Inc. CTS Durham

Agilent Technologies Biogen Caro Research Cubist Pharmaceuticals

Ajinomoto Bioheart Celsion Corp. CV Therapeutics, Inc.

Alexion Biomarin Centocor Dade Behring

Allergan Bionsense Webster, Inc. Chase Medical Daiichi

Alsius Biosite Chugai Biopharmaceuticals, Inc.

Dupont

Amgen Biotronik Coley Pharma Group Dyax

Amylin Pharmaceuticals Biotechnology General Corp

Conceptis Echosens, Inc.

Ark Therapeutics, Ltd. Boehringer Ingleheim Conor Medsystems, Inc. Eclipse Surgical Technologies

DisclosuresRobert M. Califf, MD, MACC

Edwards Lifesciences Genzyme Corporation Inhibitex Medco Health Solutions

Enzon Gilead INO Therapeutics Medicure

Ernst and Young GlaxoSmithKline Integris Medi-Flex, Inc.

Esai Guidant InterMune Pharmaceuticals Medimmune

Ev3, Inc. Guilford Pharmaceuticals ISIS Pharmaceuticals Medtronic

Evalve, Inc. Hemosol IOMED Medtronic Vascular, Inc.

First Circle Medical, Inc. Hewlett Packard Johnson & Johnson Merck

First Horizon Human Genome Sciences Jomed, Inc. MicroMed Tech, Inc.

Flow Cardia, Inc. Humana KAI Pharmaceuticals Millenium Pharmaceutical

Fox Hollow Pharmaceuticals

IDB Medical Kerberos Proximal, Inc. Mitsubishi

Fujisawa Idun Pharmaceuticals, Inc. King Pharmaceuticals Mycosol, Inc.

Genentech Immunex Kuhera Myogen

General Electric Healthcare

Indenix Pharmaceuticals Lilly NABI

General Electric Medical Systems

INFORMD, Inc. Lumen Biomedical NitroMed

Genome Canada InfraReDx MedAcoustics NITROX

DisclosuresRobert M. Califf, MD, MACC

NovaCardia, Inc. Regado Biosciences, Inc.

Summit Vicuron Pharmaceutical

Novartis, AG Group Roche Diagnostic Corp Suneis Wyeth-Ayerst

Novartis Pharmaceutical Roche Holdings, Ltd. Synaptic XOMA

Organon International Roche Labs Synthetic Blood International Xsira Pharmaceutical

Ortho Biotech Salix Pharmaceuticals Terumo Corp XTL Biopharmaceuticals

Osiris Therapeutics, Inc. Sanofi Pasteur The Medicines Company Xylum

Otsuka America Pharmaceutical, Inc.

Sanofi-Aventis Theravance Yamanouchi

Pathway Medical Tech Sanofi-Synthelabo TherOx, Inc.

Pfizer Schering-Plough Titan Pharmaceuticals, Inc.

Pharmacia/Upjohn Scios Valeant Pharmaceuticals

Pharmanetics, Inc. Searle Valentis, Inc.

Pharsight Sicel Technologies Velocimed

Proctor and Gamble Siemens Veridex

Prometheus SmithKlineBeecham Vertex Pharmaceuticals

Recom Managed Systems Spectranetics VIASYS Healthcare, Inc.

DisclosuresRobert M. Califf, MD, MACC

Alexion Pharm Medtronic

Amer Bioscience Novartis

AstraZeneca Pfizer

Atherogenics Pharmacia Upjohn

Biosite Philips

Centocor Orphan Therapeutic

Converge Medical Sankyo

Cordis Sanofi

Dr. Reddy’s Laboratory Scios

Eli Lilly * Takeda America

GlaxoSmithKline The Medicines Company

Glaxo Wellcome Vasogenix

Guilford

DisclosuresA. Michael Lincoff, MD, FACC

19901990 19921992 19941994 19961996 19981998 20002000 2002200219901990

ACC/AHAACC/AHAAMI AMI

R. GunnarR. Gunnar

19941994AHCPR/AHCPR/NHLBINHLBI

UA UA E. BraunwaldE. Braunwald

19961996 19991999 RevRev UpdUpd ACC/AHA AMI ACC/AHA AMI T. Ryan T. Ryan

2004 2004 20072007 Rev Rev Upd Upd ACC/AHA STEMI ACC/AHA STEMI

E. AntmanE. Antman

2000 2002 2000 2002 2007 2007 Rev UpdRev Upd RevRev

ACC/AHA UA/NSTEMI ACC/AHA UA/NSTEMI E. Braunwald J. AndersonE. Braunwald J. Anderson

20042004 20072007

Figure 1. Evolution of Guidelines for Management of Patients with AMI

The first guideline published by the ACC/AHA described the management of patients with acute myocardial infarction (AMI). The subsequent three documents were the Agency for Healthcare and Quality/National Heart, Lung and Blood Institute sponsored guideline on management of unstable angina (UA), the revised/updated ACC/AHA guideline on AMI, and the revised/updated ACC/AHA guideline on unstable angina/non-ST segment myocardial infarction (UA/NSTEMI). The present guideline is a revision and deals strictly with the management of patients presenting with ST segment elevation myocardial infarction (STEMI). The names of the chairs of the writing committees for each of the guidelines are shown at the bottom of each box. Rev, Revised; Upd, Update

Evolution of Guidelines for ACS

Hospitalizations in the U.S. Due to Acute Coronary Syndromes (ACS)

Acute Coronary Syndromes*

1.57 Million Hospital Admissions - ACS

UA/NSTEMI† STEMI

1.24 million Admissions per year

.33 million Admissions per year

Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69-171. *Primary and secondary diagnoses. †About 0.57 million

NSTEMI and 0.67 million UA.

Risk Stratification

Risk Stratification

1. Integral prerequisite to decision makinga) Intensive initial assessmentb) Continuous clinical assessmentc) Targeted ECG and marker data

2. Risk based on contingent probabilitiesa) Probability of obstructive CAD causing ischemiab) Risk given presence of obstructive CAD

3. Risk scores should be a routine part of assessment throughout the hospital course and periodically after discharge

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?

• 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?

24h 3-4 days 6 months

Ris

k

Physiological monitoring

Periodic physical exams

Cardiac markers

ECG

Time

Risk Scores

TIMI GRACE Future

Histo

ry

AgeHypertensionDiabetesSmoking↑cholesterolFamily historyHistory of CAD

Age Continuous assessment

Pre

sen

tatio

n

Severe anginaAspirin within 7 daysElevated markersST segment deviation

Heart rateSystolic BPElevated markersHeart failureCardiac arrestElevated markersST segment deviation

New markers

Electronic health records

Early Hospital Care

Algorithm for Patients with UA/NSTEMI Managed by an Initial Invasive Strategy

Proceed to Diagnostic Angiography

ASA (Class I, LOE: A)Clopidogrel if ASA intolerant (Class I,

LOE: A)

Diagnosis of UA/NSTEMI is Likely or Definite

Invasive StrategyInitiate A/C Rx (Class I, LOE: A)

Acceptable options: enoxaparin or UFH (Class I, LOE: A) bivalirudin or fondaparinux (Class I, LOE: B)

Select Management StrategyProceed with an

Initial Conservative

Strategy

Anderson JL. J Am Coll Cardiol 2007;50:e1-157. Figure 7

A

B

B1

B2

Prior to AngiographyInitiate at least one (Class I, LOE: A) or both (Class IIa, LOE: B) of the following:

ClopidogrelIV GP IIb/IIIa inhibitor

Factors favoring admin of both clopidogrel and GP IIb/IIIa inhibitor include:

Delay to AngiographyHigh Risk Features

Early recurrent ischemic discomfort

Initiate clopidogrel (Class I, LOE: A) Consider adding IV eptifibatide or tirofiban (Class

IIb, LOE: B)

Conservative StrategyInitiate 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)

Select Management Strategy

ASA (Class I, LOE: A)Clopidogrel if ASA intolerant (Class I, LOE: A)

Diagnosis of UA/NSTEMI is Likely or Definite

Algorithm for Patients with UA/NSTEMI Managed by an Initial Conservative Strategy

Proceed with Invasive Strategy

(Continued)Anderson JL. J Am Coll Cardiol 2007;50:e1-157. Figure 8

C2

C1

A

Any subsequent events necessitating angiography?

EF greater than 0.40

Evaluate LVEF

Low Risk

Cont ASA indefinitely (Class I, LOE A) Cont clopidogrel for at least one month (Class I, LOE A) and ideally up to

1 yr (Class I, LOE B)DC IV GP IIb/IIIa if started previously (Class I, LOE A)

DC A/C Rx (Class I, LOE A)

(Class I, LOE: B)

Proceed to Dx Angiography

Yes

EF 0.40 or less Stress Test

(Class I, LOE: A)

No

Not Low Risk

(Class IIa, LOE: B)

Algorithm for Patients with UA/NSTEMI Managed by an Initial Conservative Strategy

(Continued)

Anderson JL. J Am Coll Cardiol 2007;50:e1-157. Figure 8

(Class I, LOE: A)

(Class IIa, LOE: B)

O

L

MN

K

E-1 E-2

D

(Class I,

LOE: B)

Revascularization and Late Hospital Care

• Cont ASA (Class I, LOE: A)

• DC clopidogrel 5 to 7 d prior to elective CABG (Class I, LOE: B)

• DC IV GP IIb/IIIa 4 h prior to CABG (Class I, LOE: B)

• Cont UFH (Class I, LOE: B); DC enoxaparin 12 to 24 h prior to CABG; DC fondaparinux 24 h prior to CABG; DC bivalirudin 3 h prior to CABG. Dose with UFH per institutional practice (Class I, LOE: B)

• Cont ASA (Class I, LOE A) • LD of clopidogrel if not given

pre angio (Class I, LOE: A) &• IV GP IIb/IIIa if not started

pre angio (Class I, LOE: A)

• DC A/C Rx after PCI for uncomplicated cases (Class I, LOE: B)

• Cont ASA (Class I, LOE: A)• LD of clopidogrel if not

given pre angio (Class I, LOE A)*• DC IV GP IIb/IIIa after

at least 12 h if started pre angio (Class I, LOE: B)

• Cont IV UFH for at least 48 h (Class I, LOE: A) or enoxaparin or fondaparinux for dur of hosp (LOE: A); either DC bivalirudin or cont at a dose of 0.25 mg/kg/hr for up to 72 h at physician‘s discretion (Class I, LOE: B)

Antiplatelet and A/C Rx

at physician’s discretion (Class I, LOE: C)

No significant obstructive

CAD on angiography

CAD on angiography

Medical therapyPCICABG

Select Post Angiography Management Strategy

Dx Angiography

Management after Diagnostic Angiography in Patients with UA/NSTEMI

Anderson JL. J Am Coll Cardiol 2007;50:e1-157. In press. Figure 9

G H

I

J

F

Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI

Medical Tx w/o Stent

Bare Metal Stent

Drug Eluting Stent

ASA 162 to 325 mg/d for at least 1 mo, then 75 to 162 mg/d

indefinitely (Class I LOE: A)

&Clopidogrel 75 mg/d for at least

1 mo and up to 1 yr (Class I LOE:B)

Add: Warfarin (INR 2.0 to 2.5) (Class IIb LOE: B)

Continue with dual antiplatelet tx as above.

Indication for Anticoagulation?

ASA 75 to 162 mg/d indefinitely (Class I LOE: A)

& Clopidogrel 75 mg/d at least 1 mo (Class I LOE: A) and up

to 1 yr (Class I LOE: B)

ASA 162 to 325 mg/d for at least 3 to 6 months, then 75

to 162 mg/d indefinitely (Class I LOE: A)

&

Clopidogrel 75 mg/d for at least 1 yr (Class I LOE: B)

Anderson JL. J Am Coll Cardiol 2007;50:e1-157. Figure 11.

UA/NSTEMI Patient

Groups at Discharge

Yes

No

Preparation for Discharge After UA/NSTEMI

• Antiplatelet Rx– ASA 75 - 162 mg/day– Clopidogrel 75 mg/day

• Beta Blocker• ACEI / ARB

– Especially if DM, HF, EF <40%, HTN

• Statin– LDL <100 mg/dL (ideally <70 mg/dL)

• Secondary Prevention Measures– Smoking Cessation– BP <140/90 mm HG or <130/80 mm HG for DM or chronic kidney disease

– HbA1C <7%– BMI 18.5-24.9– Physical Exercise 30-60 min at least 5 days/wk

Panel Discussion