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Charles V. Pollack Jr, MA, MD, FACEP, FAAEMCharles V. Pollack Jr, MA, MD, FACEP, FAAEM
Program ChairmanProgram ChairmanChairman, Department of Emergency MedicineChairman, Department of Emergency Medicine
Pennsylvania HospitalPennsylvania Hospital
Professor of Emergency MedicineProfessor of Emergency Medicine
University of PennsylvaniaUniversity of Pennsylvania
School of MedicineSchool of Medicine
Philadelphia, PennsylvaniaPhiladelphia, Pennsylvania
Charles V. Pollack Jr, MA, MD, FACEP, FAAEMCharles V. Pollack Jr, MA, MD, FACEP, FAAEM
Program ChairmanProgram ChairmanChairman, Department of Emergency MedicineChairman, Department of Emergency Medicine
Pennsylvania HospitalPennsylvania Hospital
Professor of Emergency MedicineProfessor of Emergency Medicine
University of PennsylvaniaUniversity of Pennsylvania
School of MedicineSchool of Medicine
Philadelphia, PennsylvaniaPhiladelphia, Pennsylvania
Cardiovascular EmergenciesCardiovascular EmergenciesNew Dimensions andNew Dimensions and
Critical Practice AdvancesCritical Practice Advances
Cardiovascular EmergenciesCardiovascular EmergenciesNew Dimensions andNew Dimensions and
Critical Practice AdvancesCritical Practice Advances
Evidence-Based Management of Acute Coronary Syndromes:Evidence-Based Management of Acute Coronary Syndromes:Optimizing Patient Outcomes in the Complex and Challenging SpherOptimizing Patient Outcomes in the Complex and Challenging Sphere
of Cardiovascular Emergency Careof Cardiovascular Emergency Care
Evidence-Based Management of Acute Coronary Syndromes:Evidence-Based Management of Acute Coronary Syndromes:Optimizing Patient Outcomes in the Complex and Challenging SphereOptimizing Patient Outcomes in the Complex and Challenging Sphere
of Cardiovascular Emergency Careof Cardiovascular Emergency Care
Getting in the Stream of ThingsGetting in the Stream of ThingsGetting in the Stream of ThingsGetting in the Stream of Things
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CME-accredited symposiumCME-accredited symposium jointly sponsored by the University ofjointly sponsored by the University ofMassachusetts Medical School and CMEducation Resources, LLCMassachusetts Medical School and CMEducation Resources, LLC
Commercial Support:Commercial Support: Sponsored by an independent educationalSponsored by an independent educational
grant from The Medicines Companygrant from The Medicines Company
Mission statement:Mission statement: Improve patient care through evidence-basedImprove patient care through evidence-based
education, expert analysis, and case study-based managementeducation, expert analysis, and case study-based management
Processes:Processes: Strives for fair balance and clinical relevance; stressesStrives for fair balance and clinical relevance; stresses
on-label indications for agents discussed, and emerging evidenceon-label indications for agents discussed, and emerging evidence
and information from recent studiesand information from recent studies
COI:COI: Full faculty disclosures provided in syllabus and at theFull faculty disclosures provided in syllabus and at the
beginning of the programbeginning of the program
Welcome and Program OverviewWelcome and Program Overview
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Program Educational ObjectivesProgram Educational ObjectivesProgram Educational ObjectivesProgram Educational Objectives
As a result of this session, emergency physicians will:As a result of this session, emergency physicians will:
Learn to identify signs, symptoms, and prognostic features of acuteLearn to identify signs, symptoms, and prognostic features of acute
coronary syndromes and related cardiovascular emergencies.coronary syndromes and related cardiovascular emergencies.
Learn to assess and implement optimal pharmacologicLearn to assess and implement optimal pharmacologic
interventions, especially antithrombotic therapy in the upstreaminterventions, especially antithrombotic therapy in the upstreamsetting, for patients presenting with manifestations of ACS andsetting, for patients presenting with manifestations of ACS and
related cardiovascular disease emergencies.related cardiovascular disease emergencies.
Learn to characterize, identify, and evaluate the safety, efficacy, andLearn to characterize, identify, and evaluate the safety, efficacy, and
side effects of myriad therapeutic options used for acute ischemicside effects of myriad therapeutic options used for acute ischemiccoronary syndromes including, aspirin, antiplatelet agents, directcoronary syndromes including, aspirin, antiplatelet agents, direct
thrombin inhibitors, UFH, LMWHs, and factor Xa inhibitors with athrombin inhibitors, UFH, LMWHs, and factor Xa inhibitors with a
focus on new 2007 ACC/AHA UA/NSTEMI Guidelinesfocus on new 2007 ACC/AHA UA/NSTEMI Guidelines
As a result of this session, emergency physicians will:As a result of this session, emergency physicians will:
Learn to identify signs, symptoms, and prognostic features of acuteLearn to identify signs, symptoms, and prognostic features of acute
coronary syndromes and related cardiovascular emergencies.coronary syndromes and related cardiovascular emergencies.
Learn to assess and implement optimal pharmacologicLearn to assess and implement optimal pharmacologic
interventions, especially antithrombotic therapy in the upstreaminterventions, especially antithrombotic therapy in the upstreamsetting, for patients presenting with manifestations of ACS andsetting, for patients presenting with manifestations of ACS and
related cardiovascular disease emergencies.related cardiovascular disease emergencies.
Learn to characterize, identify, and evaluate the safety, efficacy, andLearn to characterize, identify, and evaluate the safety, efficacy, and
side effects of myriad therapeutic options used for acute ischemicside effects of myriad therapeutic options used for acute ischemiccoronary syndromes including, aspirin, antiplatelet agents, directcoronary syndromes including, aspirin, antiplatelet agents, direct
thrombin inhibitors, UFH, LMWHs, and factor Xa inhibitors with athrombin inhibitors, UFH, LMWHs, and factor Xa inhibitors with a
focus on new 2007 ACC/AHA UA/NSTEMI Guidelinesfocus on new 2007 ACC/AHA UA/NSTEMI Guidelines
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Program FacultyProgram Faculty
Program ChairmanProgram Chairman
Charles V. Pollack Jr, MA,Charles V. Pollack Jr, MA,
MD, FACEP, FAAEMMD, FACEP, FAAEMChairman, Department ofChairman, Department of
Emergency MedicineEmergency MedicinePennsylvania HospitalPennsylvania Hospital
Professor of Emergency MedicineProfessor of Emergency Medicine
University of Pennsylvania SchoolUniversity of Pennsylvania School
of Medicineof Medicine
Philadelphia, PennsylvaniaPhiladelphia, Pennsylvania
Program ChairmanProgram Chairman
Charles V. Pollack Jr, MA,Charles V. Pollack Jr, MA,
MD, FACEP, FAAEMMD, FACEP, FAAEMChairman, Department ofChairman, Department of
Emergency MedicineEmergency MedicinePennsylvania HospitalPennsylvania Hospital
Professor of Emergency MedicineProfessor of Emergency Medicine
University of Pennsylvania SchoolUniversity of Pennsylvania School
of Medicineof Medicine
Philadelphia, PennsylvaniaPhiladelphia, Pennsylvania
Distinguished PresentersDistinguished Presenters
Judd E. Hollander, MDJudd E. Hollander, MDProfessor and Clinical Research DirectorProfessor and Clinical Research Director
Department of Emergency MedicineDepartment of Emergency Medicine
University of PennsylvaniaUniversity of Pennsylvania
Philadelphia, PennsylvaniaPhiladelphia, Pennsylvania
Sunil Rao, MD, FACCSunil Rao, MD, FACCDirector of Interventional CardiologyDirector of Interventional Cardiology
Veterans Administration Medical CenterVeterans Administration Medical CenterAssistant ProfessorAssistant Professor
Division of Cardiovascular MedicineDivision of Cardiovascular Medicine
Duke University Medical CenterDuke University Medical Center
Durham, North CarolinaDurham, North Carolina
Distinguished PresentersDistinguished Presenters
Judd E. Hollander, MDJudd E. Hollander, MDProfessor and Clinical Research DirectorProfessor and Clinical Research Director
Department of Emergency MedicineDepartment of Emergency Medicine
University of PennsylvaniaUniversity of Pennsylvania
Philadelphia, PennsylvaniaPhiladelphia, Pennsylvania
Sunil Rao, MD, FACCSunil Rao, MD, FACCDirector of Interventional CardiologyDirector of Interventional Cardiology
Veterans Administration Medical CenterVeterans Administration Medical CenterAssistant ProfessorAssistant Professor
Division of Cardiovascular MedicineDivision of Cardiovascular Medicine
Duke University Medical CenterDuke University Medical Center
Durham, North CarolinaDurham, North Carolina
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COI Faculty DisclosuresCOI Faculty Disclosures
Charles V. Pollack Jr, MA, MD, FACEP, FAAEMCharles V. Pollack Jr, MA, MD, FACEP, FAAEMGrant/Research Support: GlaxoSmithKlineConsultant: The Medicines Co., Schering-Plough, Sanofi-Aventis, BMS, GenentechSpeakers Bureau: Schering-Plough, Sanofi-Aventis, BMS, Genentech
Judd E. Hollander, MDJudd E. Hollander, MDGrant/Research Support: Sanofi-Aventis, Biosite, Scios, The Medicines CompanyGrant/Research Support: Sanofi-Aventis, Biosite, Scios, The Medicines Company
Consultant: Sanofi-Aventis, Biosite, Scios, The Medicines CompanyConsultant: Sanofi-Aventis, Biosite, Scios, The Medicines Company
Speakers Bureau: Sanofi-Aventis, Biosite, Scios, The Medicines CompanySpeakers Bureau: Sanofi-Aventis, Biosite, Scios, The Medicines Company
Sunil Rao, MD, FACCSunil Rao, MD, FACCGrant/Research Support: CordisGrant/Research Support: Cordis
Consultant: Sanofi-Aventis, The Medicines CompanyConsultant: Sanofi-Aventis, The Medicines Company
Speakers Bureau: Sanofi-Aventis, The Medicines Company, CordisSpeakers Bureau: Sanofi-Aventis, The Medicines Company, Cordis
Charles V. Pollack Jr, MA, MD, FACEP, FAAEMCharles V. Pollack Jr, MA, MD, FACEP, FAAEMGrant/Research Support: GlaxoSmithKlineConsultant: The Medicines Co., Schering-Plough, Sanofi-Aventis, BMS, GenentechSpeakers Bureau: Schering-Plough, Sanofi-Aventis, BMS, Genentech
Judd E. Hollander, MDJudd E. Hollander, MDGrant/Research Support: Sanofi-Aventis, Biosite, Scios, The Medicines CompanyGrant/Research Support: Sanofi-Aventis, Biosite, Scios, The Medicines Company
Consultant: Sanofi-Aventis, Biosite, Scios, The Medicines CompanyConsultant: Sanofi-Aventis, Biosite, Scios, The Medicines Company
Speakers Bureau: Sanofi-Aventis, Biosite, Scios, The Medicines CompanySpeakers Bureau: Sanofi-Aventis, Biosite, Scios, The Medicines Company
Sunil Rao, MD, FACCSunil Rao, MD, FACCGrant/Research Support: CordisGrant/Research Support: Cordis
Consultant: Sanofi-Aventis, The Medicines CompanyConsultant: Sanofi-Aventis, The Medicines Company
Speakers Bureau: Sanofi-Aventis, The Medicines Company, CordisSpeakers Bureau: Sanofi-Aventis, The Medicines Company, Cordis
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Acute Coronary SyndromeAcute Coronary SyndromeThe 2007 ACC/AHA UA/NSTEMI GuidelinesThe 2007 ACC/AHA UA/NSTEMI Guidelines
From the ED to CCU and Cath Lab From the ED to CCU and Cath Lab
Adherence Yields Better OutcomesAdherence Yields Better Outcomes
Acute Coronary SyndromeAcute Coronary SyndromeThe 2007 ACC/AHA UA/NSTEMI GuidelinesThe 2007 ACC/AHA UA/NSTEMI Guidelines
From the ED to CCU and Cath Lab From the ED to CCU and Cath Lab
Adherence Yields Better OutcomesAdherence Yields Better Outcomes
Charles V. Pollack Jr, MA, MD, FACEP, FAAEMCharles V. Pollack Jr, MA, MD, FACEP, FAAEM
Program ChairmanProgram ChairmanChairman, Department of Emergency MedicineChairman, Department of Emergency Medicine
Pennsylvania HospitalPennsylvania Hospital
Professor of Emergency MedicineProfessor of Emergency Medicine
University of PennsylvaniaUniversity of Pennsylvania
School of MedicineSchool of Medicine
Philadelphia, PennsylvaniaPhiladelphia, Pennsylvania
Getting in the (Up)Stream of ThingsGetting in the (Up)Stream of ThingsGetting in the (Up)Stream of ThingsGetting in the (Up)Stream of Things
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Changing the CalculationChanging the CalculationAssessing Adherence to GuidelinesAssessing Adherence to Guidelines
Changing the CalculationChanging the CalculationAssessing Adherence to GuidelinesAssessing Adherence to Guidelines
Anderson HV, Bach RG, J Am Coll Cardiol2005;46:1488-9.
We need to invert the current equationWe need to invert the current equation
to calculate an opportunity score for ACSto calculate an opportunity score for ACS
patients rather than a risk score. Patientspatients rather than a risk score. Patients
with higher baseline risks, such as thewith higher baseline risks, such as the
elderly, would have higher opportunityelderly, would have higher opportunity
scores for benefit, even allowing forscores for benefit, even allowing for
some of the greater risks from thesome of the greater risks from the
treatment.treatment.
We need to invert the current equationWe need to invert the current equation
to calculate an opportunity score for ACSto calculate an opportunity score for ACS
patients rather than a risk score. Patientspatients rather than a risk score. Patients
with higher baseline risks, such as thewith higher baseline risks, such as the
elderly, would have higher opportunityelderly, would have higher opportunity
scores for benefit, even allowing forscores for benefit, even allowing for
some of the greater risks from thesome of the greater risks from the
treatment.treatment.
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++++
Ischemic Discomfortat Rest
Ischemic Discomfortat Rest
No ST-segmentElevation
No ST-segmentElevation
Non-Q-wave MIUnstable
Angina
Q-wave MI
ST-segmentElevation
ST-segmentElevation
++ ++
( : positive cardiac biomarker)
EmergencyEmergencyDepartmentDepartment
In-hospitalIn-hospital
6-24hrs6-24hrs
PresentationPresentation
Acute Coronary SyndromesAcute Coronary SyndromesClinical Spectrum and PresentationClinical Spectrum and Presentation
Acute Coronary SyndromesAcute Coronary SyndromesClinical Spectrum and PresentationClinical Spectrum and Presentation
NSTEMINSTEMI
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SYNERGY
LMWHLMWH
ESSENCEESSENCE
19941994 1995199519961996 19971997 1998199819991999 20002000 20022002 200200
3320042004 20052005 2006200620012001
CURECURE
ClopidogrelClopidogrel
Bleeding riskBleeding risk
Ischemic riskIschemic risk
GP IIb/IIIaGP IIb/IIIa
blockersblockers
PRISM-PLUSPRISM-PLUS
PURSUITPURSUIT
ACUITYTACTICS TIMI-18TACTICS TIMI-18
Early invasiveEarly invasive
PCIPCI ~ 5% stents~ 5% stents ~85% stents~85% stents Drug-eluting stentsDrug-eluting stents
ISAR-REACT 2
Milestones in ACS Management
OASIS-5
[ Fondaparinux ][ Fondaparinux ]
Anti-Thrombin RxAnti-Thrombin Rx
Anti-Platelet RxAnti-Platelet Rx
Treatment StrategyTreatment Strategy
HeparinHeparin
AspirinAspirin
ConservativeConservative
ICTUS
BivalirudinBivalirudin
REPLACE 2REPLACE 2
Ada ted from and with the courtes of Steven Manoukian MDAdapted from and with the courtesy of Steven Manoukian, MDAdapted from and with the courtesy of Steven Manoukian, MDAdapted from and with the courtesy of Steven Manoukian, MD
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We Must Risk Stratify PatientsWe Must Risk Stratify Patients
with Chest Painwith Chest Pain
Three levels of risk stratification are pertinentThree levels of risk stratification are pertinentto Emergency Department Managementto Emergency Department Management
LowLow, intermediate, or high risk, intermediate, or high risk that ischemic symptoms arethat ischemic symptoms are
a result of CADa result of CAD
Low, intermediateLow, intermediate, or, orhigh riskhigh risk of short-term death orof short-term death or
nonfatal MI from ACSnonfatal MI from ACS
Dynamic, ongoing risk-oriented evaluationDynamic, ongoing risk-oriented evaluation of low- orof low- orintermediate-risk patients for conversion to high-riskintermediate-risk patients for conversion to high-risk
statusstatus that is linked to intensity of treatmentthat is linked to intensity of treatment
Three levels of risk stratification are pertinentThree levels of risk stratification are pertinentto Emergency Department Managementto Emergency Department Management
LowLow, intermediate, or high risk, intermediate, or high risk that ischemic symptoms arethat ischemic symptoms are
a result of CADa result of CAD
Low, intermediateLow, intermediate, or, orhigh riskhigh risk of short-term death orof short-term death ornonfatal MI from ACSnonfatal MI from ACS
Dynamic, ongoing risk-oriented evaluationDynamic, ongoing risk-oriented evaluation of low- orof low- orintermediate-risk patients for conversion to high-riskintermediate-risk patients for conversion to high-risk
statusstatus that is linked to intensity of treatmentthat is linked to intensity of treatment
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Dynamic Risk Stratification ToolsDynamic Risk Stratification ToolsDynamic Risk Stratification ToolsDynamic Risk Stratification Tools
History and PhysicalHistory and Physical Standard EKG and non-standard EKG leadsStandard EKG and non-standard EKG leads
15-lead ECGs should, perhaps, be standard in all but very-15-lead ECGs should, perhaps, be standard in all but very-
low-risk patientslow-risk patients
BiomarkersBiomarkers CPK-MB, Troponins I and T, MyoglobinCPK-MB, Troponins I and T, Myoglobin
Ischemia-Modified AlbuminIschemia-Modified Albumin
Non-Invasive ImagingNon-Invasive Imaging
EchocardiogramEchocardiogram Stress testingStress testing
Technetium-99m-sestamibiTechnetium-99m-sestamibi
Predictive Indices/SchemesPredictive Indices/Schemes
Better as research tools than for real-time clinical decision-Better as research tools than for real-time clinical decision-makingmaking
History and PhysicalHistory and Physical Standard EKG and non-standard EKG leadsStandard EKG and non-standard EKG leads
15-lead ECGs should, perhaps, be standard in all but very-15-lead ECGs should, perhaps, be standard in all but very-low-risk patientslow-risk patients
BiomarkersBiomarkers CPK-MB, Troponins I and T, MyoglobinCPK-MB, Troponins I and T, Myoglobin
Ischemia-Modified AlbuminIschemia-Modified Albumin
Non-Invasive ImagingNon-Invasive Imaging
EchocardiogramEchocardiogram Stress testingStress testing
Technetium-99m-sestamibiTechnetium-99m-sestamibi
Predictive Indices/SchemesPredictive Indices/Schemes
Better as research tools than for real-time clinical decision-Better as research tools than for real-time clinical decision-
makingmaking
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Braunwald E, Antman EM, Beasley JW, et al: ACC/AHABraunwald E, Antman EM, Beasley JW, et al: ACC/AHAguidelines for the management of patients with unstableguidelines for the management of patients with unstable
angina and non-ST-segment elevation myocardial infarction:angina and non-ST-segment elevation myocardial infarction:
a report of the American College of Cardiology/Americana report of the American College of Cardiology/American
Heart Association Task Force on Practice GuidelinesHeart Association Task Force on Practice Guidelines
(Committee on the Management of Patients with Unstable(Committee on the Management of Patients with Unstable
Angina).Angina). J Am Coll CardiolJ Am Coll Cardiol2000;36:970-1062 (2002 update2000;36:970-1062 (2002 update
atat www.acc.orgwww.acc.org; summary in; summary in CirculationCirculation 2002;106:1893-2002;106:1893-
1900)1900)
Pollack CV, Roe MT, Peterson ED: 2002 Update to thePollack CV, Roe MT, Peterson ED: 2002 Update to the
ACC/AHA guidelines for the management of patients withACC/AHA guidelines for the management of patients with
unstable angina and non-ST-segment elevation myocardialunstable angina and non-ST-segment elevation myocardial
infarction: Implications for emergency department practice.infarction: Implications for emergency department practice.
Ann Emerg MedAnn EmergMed2003;41:355-692003;41:355-69
Braunwald E, Antman EM, Beasley JW, et al: ACC/AHABraunwald E, Antman EM, Beasley JW, et al: ACC/AHAguidelines for the management of patients with unstableguidelines for the management of patients with unstable
angina and non-ST-segment elevation myocardial infarction:angina and non-ST-segment elevation myocardial infarction:
a report of the American College of Cardiology/Americana report of the American College of Cardiology/American
Heart Association Task Force on Practice GuidelinesHeart Association Task Force on Practice Guidelines
(Committee on the Management of Patients with Unstable(Committee on the Management of Patients with UnstableAngina).Angina). J Am Coll CardiolJ Am Coll Cardiol2000;36:970-1062 (2002 update2000;36:970-1062 (2002 update
atat www.acc.orgwww.acc.org; summary in; summary in CirculationCirculation 2002;106:1893-2002;106:1893-
1900)1900)
Pollack CV, Roe MT, Peterson ED: 2002 Update to thePollack CV, Roe MT, Peterson ED: 2002 Update to the
ACC/AHA guidelines for the management of patients withACC/AHA guidelines for the management of patients with
unstable angina and non-ST-segment elevation myocardialunstable angina and non-ST-segment elevation myocardial
infarction: Implications for emergency department practice.infarction: Implications for emergency department practice.
Ann Emerg MedAnn EmergMed2003;41:355-692003;41:355-69
NSTE ACS Optimal Therapy: 2002NSTE ACS Optimal Therapy: 2002NSTE ACS Optimal Therapy: 2002NSTE ACS Optimal Therapy: 2002
http://www.pbase.com/es839145/animated_waterhttp://www.pbase.com/es839145/animated_waterhttp://www.pbase.com/es839145/animated_waterhttp://www.pbase.com/es839145/animated_waterhttp://www.pbase.com/es839145/animated_waterhttp://www.pbase.com/es839145/animated_waterhttp://www.pbase.com/es839145/animated_water -
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II IIaIIa IIbIIb IIIIII
The GuidelinesThe GuidelinesClasses of RecommendationsClasses of Recommendations
The GuidelinesThe GuidelinesClasses of RecommendationsClasses of Recommendations
Intervention is useful and effectiveIntervention is useful and effective
Evidence supportive; awaitingEvidence supportive; awaiting
confirming dataconfirming data
Evidence conflicts/opinions differ;Evidence conflicts/opinions differ;
neutral statementneutral statement
Intervention is not useful/effective andIntervention is not useful/effective andmay be harmfulmay be harmful
Intervention is useful and effectiveIntervention is useful and effective
Evidence supportive; awaitingEvidence supportive; awaiting
confirming dataconfirming data
Evidence conflicts/opinions differ;Evidence conflicts/opinions differ;
neutral statementneutral statement
Intervention is not useful/effective andIntervention is not useful/effective andmay be harmfulmay be harmful
E id B d A h ACSE id B d A h t ACS
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Evidence-Based Approach to ACSEvidence-Based Approach to ACSWeighing the EvidenceWeighing the Evidence
Class I:Class I: Benefit > > RiskBenefit > > Risk
Class IIa:Class IIa: Benefit > RiskBenefit > Risk
Class IIb:Class IIb: BenefitBenefit >> RiskRisk
Class III:Class III: RiskRisk >> BenefitBenefit
Class I:Class I: Benefit > > RiskBenefit > > Risk
Class IIa:Class IIa: Benefit > RiskBenefit > Risk
Class IIb:Class IIb: BenefitBenefit >> RiskRisk
Class III:Class III: RiskRisk >> BenefitBenefit
Th G id li Th G id li
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The GuidelinesThe GuidelinesWeighing the EvidenceWeighing the Evidence
Weight of Evidence GradesWeight of Evidence Grades
= Data from many large, randomized= Data from many large, randomized
trialstrials
== Data from fewer, smaller randomizedData from fewer, smaller randomized
trials, careful analyses oftrials, careful analyses of
nonrandomized studies,nonrandomized studies,
observational registriesobservational registries
== Expert consensusExpert consensus
GWh t D Th G id li MWh t D Th G id li M
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What Do The Guidelines MeanWhat Do The Guidelines Mean
for Emergency Medicine Practice?for Emergency Medicine Practice?
What Do The Guidelines MeanWhat Do The Guidelines Mean
for Emergency Medicine Practice?for Emergency Medicine Practice?
Objective approach to risk stratification andObjective approach to risk stratification and
treatmenttreatment
Driven by risk, not patient geographyDriven by risk, not patient geography
MultidisciplinaryMultidisciplinary
Provides a foundation for communication,Provides a foundation for communication,
collaboration, and continuum of care from EDcollaboration, and continuum of care from ED
to cardiology serviceto cardiology service
2007 Guidelines push for that continuum to be2007 Guidelines push for that continuum to be
compressed in durationcompressed in duration
Objective approach to risk stratification andObjective approach to risk stratification and
treatmenttreatment
Driven by risk, not patient geographyDriven by risk, not patient geography
MultidisciplinaryMultidisciplinary
Provides a foundation for communication,Provides a foundation for communication,
collaboration, and continuum of care from EDcollaboration, and continuum of care from ED
to cardiology serviceto cardiology service
2007 Guidelines push for that continuum to be2007 Guidelines push for that continuum to be
compressed in durationcompressed in duration
Wh t D Th G id li MWh t D Th G id li M
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AcuteAcute
CoronaryCoronary
SyndromeSyndrome
AcuteAcute
CoronaryCoronary
SyndromeSyndrome
What Do The Guidelines MeanWhat Do The Guidelines Mean
for Emergency Medicine Practice?for Emergency Medicine Practice?
GWh t D Th G id li MWh t D Th G id li MWh t D Th G id li M
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AcuteAcute
ControversyControversy
SyndromeSyndrome
AcuteAcute
ControversyControversy
SyndromeSyndrome
What Do The Guidelines MeanWhat Do The Guidelines Mean
for Emergency Medicine Practice?for Emergency Medicine Practice?
What Do The Guidelines MeanWhat Do The Guidelines Mean
for Emergency Medicine Practice?for Emergency Medicine Practice?
Wh t D Th G id li MWh t D Th G id li M
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AcuteAcute
ConfusionalConfusional
SyndromeSyndrome
AcuteAcute
ConfusionalConfusional
SyndromeSyndrome
What Do The Guidelines MeanWhat Do The Guidelines Mean
for Emergency Medicine Practice?for Emergency Medicine Practice?
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Acute Confounded SyndromeAcute Confounded Syndrome
The Writing Committee believes thatThe Writing Committee believes that inadequateinadequateunconfounded, comparative information is availableunconfounded, comparative information is available toto
recommend a preferred [anticoagulation] regimen whenrecommend a preferred [anticoagulation] regimen whenan early, invasive strategy is used for UA/NSTEMI, andan early, invasive strategy is used for UA/NSTEMI, and
physician and health care system preference, togetherphysician and health care system preference, together
with individualized patient application, is advised.with individualized patient application, is advised.
Acute Confounded SyndromeAcute Confounded Syndrome
The Writing Committee believes thatThe Writing Committee believes that inadequateinadequate
unconfounded, comparative information is availableunconfounded, comparative information is available toto
recommend a preferred [anticoagulation] regimen whenrecommend a preferred [anticoagulation] regimen whenan early, invasive strategy is used for UA/NSTEMI, andan early, invasive strategy is used for UA/NSTEMI, and
physician and health care system preference, togetherphysician and health care system preference, together
with individualized patient application, is advised.with individualized patient application, is advised.
UA/NSTEMI Strategy OverviewUA/NSTEMI Strategy OverviewUA/NSTEMI Strategy OverviewUA/NSTEMI Strategy Overview
ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007, Circulation.ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007, Circulation.
Wh t D Th G id li MWh t D Th G id li MWh t D Th G id li MWhat Do The Guidelines Mean
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AcuteAcute
ContentiousnessContentiousness
SyndromeSyndrome
AcuteAcute
ContentiousnessContentiousness
SyndromeSyndrome
What Do The Guidelines MeanWhat Do The Guidelines Mean
for Emergency Medicine Practice?for Emergency Medicine Practice?
What Do The Guidelines MeanWhat Do The Guidelines Mean
for Emergency Medicine Practice?for Emergency Medicine Practice?
Wh t D Th G id li MWh t D Th G id li MWh t D Th G id li MWhat Do The Guidelines Mean
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AcuteAcute
CollaborationCollaboration
SyndromeSyndrome
AcuteAcute
CollaborationCollaboration
SyndromeSyndrome
What Do The Guidelines MeanWhat Do The Guidelines Mean
for Emergency Medicine Practice?for Emergency Medicine Practice?
What Do The Guidelines MeanWhat Do The Guidelines Mean
for Emergency Medicine Practice?for Emergency Medicine Practice?
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Big Picture: Early Invasive Vs.Big Picture: Early Invasive Vs.
Initial Conservative TherapyInitial Conservative Therapy
An early invasive strategy (i.e., diagnostic angiography with intent toAn early invasive strategy (i.e., diagnostic angiography with intent to
perform revascularization) is indicated in initially stabilized UA/NSTEMIperform revascularization) is indicated in initially stabilized UA/NSTEMI
patients (without serious comorbidities or contraindications to suchpatients (without serious comorbidities or contraindications to such
procedures)procedures) who have an elevated risk for clinical eventswho have an elevated risk for clinical events..
In initially stabilized patients, anIn initially stabilized patients, an initially conservative (i.e., a selectivelyinitially conservative (i.e., a selectively
invasive) strategy may be consideredinvasive) strategy may be considered as a treatment strategy foras a treatment strategy for
UA/NSTEMI patients (without serious comorbidities or contraindicationsUA/NSTEMI patients (without serious comorbidities or contraindications
to such procedures) who have an elevated risk for clinical events,to such procedures) who have an elevated risk for clinical events,
including those who are troponin positiveincluding those who are troponin positive..
The decision to implement an initial conservative (vs. initial invasive)The decision to implement an initial conservative (vs. initial invasive)
strategy in these patients may be made bystrategy in these patients may be made by considering physician andconsidering physician and
patient preferencepatient preference..
Big Picture: Early Invasive Vs.Big Picture: Early Invasive Vs.
Initial Conservative TherapyInitial Conservative Therapy
An early invasive strategy (i.e., diagnostic angiography with intent toAn early invasive strategy (i.e., diagnostic angiography with intent to
perform revascularization) is indicated in initially stabilized UA/NSTEMIperform revascularization) is indicated in initially stabilized UA/NSTEMI
patients (without serious comorbidities or contraindications to suchpatients (without serious comorbidities or contraindications to such
procedures)procedures) who have an elevated risk for clinical eventswho have an elevated risk for clinical events..
In initially stabilized patients, anIn initially stabilized patients, an initially conservative (i.e., a selectivelyinitially conservative (i.e., a selectively
invasive) strategy may be consideredinvasive) strategy may be considered as a treatment strategy foras a treatment strategy for
UA/NSTEMI patients (without serious comorbidities or contraindicationsUA/NSTEMI patients (without serious comorbidities or contraindications
to such procedures) who have an elevated risk for clinical events,to such procedures) who have an elevated risk for clinical events,
including those who are troponin positiveincluding those who are troponin positive..
The decision to implement an initial conservative (vs. initial invasive)The decision to implement an initial conservative (vs. initial invasive)
strategy in these patients may be made bystrategy in these patients may be made by considering physician andconsidering physician and
patient preferencepatient preference..
UA/NSTEMI Strategy OverviewUA/NSTEMI Strategy OverviewUA/NSTEMI Strategy OverviewUA/NSTEMI Strategy Overview
ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007,ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007, Circulation.Circulation.ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007,ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007, Circulation.Circulation.
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Algorithm for Evaluation and Management ofAlgorithm for Evaluation and Management of
Patients Suspected of Having ACSPatients Suspected of Having ACS
ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007, Circulation.
AASymptoms Suggestive ofSymptoms Suggestive of
ACSACS
Symptoms Suggestive ofSymptoms Suggestive of
ACSACS
NoncardiacNoncardiac
DiagnosisDiagnosis
NoncardiacNoncardiac
DiagnosisDiagnosis
UnstableUnstable
AnginaAngina
UnstableUnstable
AnginaAngina
Treatment asTreatment as
indicated byindicated by
alternativealternative
diagnosisdiagnosis
Treatment asTreatment as
indicated byindicated by
alternativealternative
diagnosisdiagnosis
See ACC/AHASee ACC/AHA
Guidelines forGuidelines for
Chronic StableChronic Stable
AnginaAngina
See ACC/AHASee ACC/AHA
Guidelines forGuidelines for
Chronic StableChronic Stable
AnginaAngina
BIBI B2B2
PossiblePossible
ACSACS
PossiblePossible
ACSACS
DefiniteDefinite
ACSACS
DefiniteDefinite
ACSACS
B3B3 B4B4
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Algorithm for Evaluation and Management ofAlgorithm for Evaluation and Management of
Patients Suspected of Having ACSPatients Suspected of Having ACS
Possible ACSPossible ACSPossible ACSPossible ACS
Nondiagnostic ECGNondiagnostic ECG
Normal initial serum cardiac biomarkersNormal initial serum cardiac biomarkers
Nondiagnostic ECGNondiagnostic ECG
Normal initial serum cardiac biomarkersNormal initial serum cardiac biomarkers
OBSERVEOBSERVE
12 hours or more from12 hours or more fromsymptom onsetsymptom onset
OBSERVEOBSERVE
12 hours or more from12 hours or more fromsymptom onsetsymptom onset
No recurrent pain,No recurrent pain,
negative follow-upnegative follow-up
studiesstudies
No recurrent pain,No recurrent pain,
negative follow-upnegative follow-up
studiesstudies
Recurrent pain, positiveRecurrent pain, positive
follow-up studiesfollow-up studies
Diagnosis OF ACSDiagnosis OF ACS
confirmedconfirmed
Recurrent pain, positiveRecurrent pain, positive
follow-up studiesfollow-up studies
Diagnosis OF ACSDiagnosis OF ACS
confirmedconfirmed
Admit to hospitalAdmit to hospital
Manage via acuteManage via acute
ischemia pathwayischemia pathway
Admit to hospitalAdmit to hospital
Manage via acuteManage via acute
ischemia pathwayischemia pathway
Stress study to provoke ischemiaStress study to provoke ischemia
Consider evaluation of LV function ifConsider evaluation of LV function if
ischemia is present (tests may beischemia is present (tests may be
performed either prior to discharge or asperformed either prior to discharge or as
outpatientoutpatient
Stress study to provoke ischemiaStress study to provoke ischemia
Consider evaluation of LV function ifConsider evaluation of LV function if
ischemia is present (tests may beischemia is present (tests may be
performed either prior to discharge or asperformed either prior to discharge or as
outpatientoutpatient
D1D1
E1E1
F2F2F1F1
G1G1
H3H3
ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007, Circulation.
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Algorithm for Evaluation and Management ofAlgorithm for Evaluation and Management of
Patients Suspected of Having ACSPatients Suspected of Having ACS
PositivePositive
Diagnosis of ACSDiagnosis of ACS
confirmed or highlyconfirmed or highly
likelylikely
PositivePositive
Diagnosis of ACSDiagnosis of ACS
confirmed or highlyconfirmed or highly
likelylikely
Admin to hospitalAdmin to hospital
Manage viaManage via
acute ischemia pathwayacute ischemia pathway
Admin to hospitalAdmin to hospital
Manage viaManage via
acute ischemia pathwayacute ischemia pathway
H2H2 H3H3
Stress study to provoke ischemiaStress study to provoke ischemia
Consider evaluation of LV function ifConsider evaluation of LV function ifischemia is present (tests may beischemia is present (tests may be
performed either prior to discharge or asperformed either prior to discharge or as
outpatientoutpatient
Stress study to provoke ischemiaStress study to provoke ischemia
Consider evaluation of LV function ifConsider evaluation of LV function ifischemia is present (tests may beischemia is present (tests may be
performed either prior to discharge or asperformed either prior to discharge or as
outpatientoutpatient
G1G1
NegativeNegativePotential diagnoses:Potential diagnoses:
Nonischemic discomfort;Nonischemic discomfort;
low-risk ACSlow-risk ACS
NegativeNegativePotential diagnoses:Potential diagnoses:
Nonischemic discomfort;Nonischemic discomfort;
low-risk ACSlow-risk ACS
Arrangements forArrangements for
outpatient follow-upoutpatient follow-up
Arrangements forArrangements for
outpatient follow-upoutpatient follow-up
H1H1
I1I1
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Specific Recommendations, ClassSpecific Recommendations, Class
Designation, and Levels OfDesignation, and Levels Of
EvidenceEvidence
Initial Invasive Strategy: Whats New?Initial Invasive Strategy: Whats New?
Specific Recommendations, ClassSpecific Recommendations, Class
Designation, and Levels OfDesignation, and Levels Of
EvidenceEvidence
Initial Invasive Strategy: Whats New?Initial Invasive Strategy: Whats New?
UA/NSTEMI Strategy OverviewUA/NSTEMI Strategy Overview
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New Strategies: AnticoagulantsNew Strategies: Anticoagulants
Two new anticoagulants,Two new anticoagulants, fondaparinux andfondaparinux andbivalirudinbivalirudin, have undergone, have undergone favorable testing infavorable testing in
clinical trials and are recommendedclinical trials and are recommended as alternativesas alternatives
to unfractionated heparin (UFH) and low-molecular-to unfractionated heparin (UFH) and low-molecular-
weight heparins (LMWHs) for specific or moreweight heparins (LMWHs) for specific or more
general applications.general applications.
New Strategies: AnticoagulantsNew Strategies: Anticoagulants
Two new anticoagulants,Two new anticoagulants, fondaparinux andfondaparinux andbivalirudinbivalirudin, have undergone, have undergone favorable testing infavorable testing in
clinical trials and are recommendedclinical trials and are recommended as alternativesas alternatives
to unfractionated heparin (UFH) and low-molecular-to unfractionated heparin (UFH) and low-molecular-
weight heparins (LMWHs) for specific or moreweight heparins (LMWHs) for specific or more
general applications.general applications.
UA/NSTEMI Strategy OverviewUA/NSTEMI Strategy Overview
ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007, Circulation.
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Algorithm for Patients With UA/NSTEMIAlgorithm for Patients With UA/NSTEMI
Managed by an Initial Invasive StrategyManaged by an Initial Invasive Strategy
Diagnosis of UA/NSTEMI is Likely or DefiniteDiagnosis of UA/NSTEMI is Likely or DefiniteDiagnosis of UA/NSTEMI is Likely or DefiniteDiagnosis of UA/NSTEMI is Likely or Definite
ASA (Class I, LOE:A)*ASA (Class I, LOE:A)*
Clopidogrel if ASA intolerant (Class I, LOE: A)Clopidogrel if ASA intolerant (Class I, LOE: A)
ASA (Class I, LOE:A)*ASA (Class I, LOE:A)*
Clopidogrel if ASA intolerant (Class I, LOE: A)Clopidogrel if ASA intolerant (Class I, LOE: A)
Select Management StrategySelect Management StrategySelect Management StrategySelect Management Strategy
Invasive StrategyInvasive Strategy
Initiate anticoagulant therapy (Class I, LOE: A):Initiate anticoagulant therapy (Class I, LOE: A):
Acceptable options*: enoxaparin or UFH (Class I,Acceptable options*: enoxaparin or UFH (Class I,LOE: A), bivalirudin or fondaparinux are preferableLOE: A), bivalirudin or fondaparinux are preferable
(Class I, LOE: B)(Class I, LOE: B)
Invasive StrategyInvasive Strategy
Initiate anticoagulant therapy (Class I, LOE: A):Initiate anticoagulant therapy (Class I, LOE: A):
Acceptable options*: enoxaparin or UFH (Class I,Acceptable options*: enoxaparin or UFH (Class I,
LOE: A), bivalirudin or fondaparinux are preferableLOE: A), bivalirudin or fondaparinux are preferable
(Class I, LOE: B)(Class I, LOE: B)
InitialInitial
ConservativeConservative
StrategyStrategy
InitialInitial
ConservativeConservative
StrategyStrategy
AAAA
B1B1B1B1
ACC/AHA 2007 Guidelines for the Management of UA/NSTEMI. August 6, 2007, Circulation.
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Algorithm for Patients With UA/NSTEMIAlgorithm for Patients With UA/NSTEMI
Managed by an Initial Invasive StrategyManaged by an Initial Invasive Strategy
Prior to AngiographyPrior to Angiography
Initiate at least one (Class I, LOE: A) orInitiate at least one (Class I, LOE: A) or
Both (Class IIa, LOE: B) of the following:Both (Class IIa, LOE: B) of the following:
Clopidogrel*Clopidogrel*
IV GP IIb/IIIa inhibitor*IV GP IIb/IIIa inhibitor*
Factors favoring administration of both clopidogrelFactors favoring administration of both clopidogrel
and GP IIb/IIIa inhibitor include:and GP IIb/IIIa inhibitor include:
Delay to angiographyDelay to angiography
High risk featuresHigh risk featuresEarly recurrent ischemic discomfortEarly recurrent ischemic discomfort
Prior to AngiographyPrior to Angiography
Initiate at least one (Class I, LOE: A) orInitiate at least one (Class I, LOE: A) or
Both (Class IIa, LOE: B) of the following:Both (Class IIa, LOE: B) of the following:
Clopidogrel*Clopidogrel*
IV GP IIb/IIIa inhibitor*IV GP IIb/IIIa inhibitor*
Factors favoring administration of both clopidogrelFactors favoring administration of both clopidogrel
and GP IIb/IIIa inhibitor include:and GP IIb/IIIa inhibitor include:
Delay to angiographyDelay to angiography
High risk featuresHigh risk featuresEarly recurrent ischemic discomfortEarly recurrent ischemic discomfort
Diagnostic AngiographyDiagnostic AngiographyDiagnostic AngiographyDiagnostic Angiography
B2B2B2B2
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Welcome To This Program!Welcome To This Program!
Move from confusion, controversy, andMove from confusion, controversy, and
contentiousness tocontentiousness to collaboration andcollaboration and
more evidence-based caremore evidence-based care
Give emergency physicians familiarityGive emergency physicians familiarity
they need with ACC/AHA 2007 UA/NSTEMIthey need with ACC/AHA 2007 UA/NSTEMI
Guidelines in order to:Guidelines in order to:q (1) Treat patients optimally and;(1) Treat patients optimally and;
q (2) Work effectively and collegially with their(2) Work effectively and collegially with their
cardiology consultantscardiology consultants
Move from confusion, controversy, andMove from confusion, controversy, and
contentiousness tocontentiousness to collaboration andcollaboration and
more evidence-based caremore evidence-based care
Give emergency physicians familiarityGive emergency physicians familiarity
they need with ACC/AHA 2007 UA/NSTEMIthey need with ACC/AHA 2007 UA/NSTEMI
Guidelines in order to:Guidelines in order to:q (1) Treat patients optimally and;(1) Treat patients optimally and;
q (2) Work effectively and collegially with their(2) Work effectively and collegially with their
cardiology consultantscardiology consultants
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Recent Clinical Trials in STEMIRecent Clinical Trials in STEMI
and NSTEMIand NSTEMIWhat New Evidence Tells Us and ImplicationsWhat New Evidence Tells Us and Implications
for ED Cardiovascular Managementfor ED Cardiovascular Management
Recent Clinical Trials in STEMIRecent Clinical Trials in STEMI
and NSTEMIand NSTEMIWhat New Evidence Tells Us and ImplicationsWhat New Evidence Tells Us and Implications
for ED Cardiovascular Managementfor ED Cardiovascular Management
Judd E. Hollander, MDJudd E. Hollander, MDProfessor and Clinical Research DirectorProfessor and Clinical Research Director
Department of Emergency MedicineDepartment of Emergency Medicine
University of PennsylvaniaUniversity of Pennsylvania
Getting in the Stream of ThingsGetting in the Stream of Things
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ACS: Recent Clinical Trials inACS: Recent Clinical Trials in
STEMISTEMI and NSTEMIand NSTEMI
ACS: Recent Clinical Trials inACS: Recent Clinical Trials in
STEMISTEMI and NSTEMIand NSTEMI
Getting in the (Up)Stream of ThingsGetting in the (Up)Stream of Things
PCIPCI versusversus FibrinolysisFibrinolysis
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8.57.3 7.2
22.0
2.0
7.2
4.92.8
6.8
1.0
0.0
5.0
10.0
15.0
20.0
25.0
Death Death
SHOCK
excl.
Reinfarction Recurrent
ischemia
Stroke
Percent(%)
Lysis
PCI
PCIPCI versusversus FibrinolysisFibrinolysis
Systematic OverviewSystematic Overview
Short term (4-6 weeks)
Keeley EC, Boura JA, Grines CL. Lancet. 2003.
P=0.0002P=0.0002P=0.0003P=0.0003 P
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5.9%
2.2%
3.7%
5.7%
0%
2%
4%
6%
8%
10%
2 Hrs
(n=374)
30-daymort
ality
Pre-hosp tPA
PCI
7.4%
15.3%
7.3%6.0%
0%
5%
10%
15%
20%
3 Hrs
(n=299)
30-daymort
ality
Lytic (SK)
Transfer for PCI
Early Presenting Patients Early Presenting Patients Primary PCIPrimary PCI versusversus FibrinolyticsFibrinolytics
Early Presenting Patients Early Presenting Patients Primary PCIPrimary PCI versusversus FibrinolyticsFibrinolytics
p=0.058p=0.058 p=0.47p=0.47
CAPTIMCAPTIM
p
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Mortality Rates with Primary PCI as aMortality Rates with Primary PCI as a
Function of PCI Time DelayFunction of PCI Time Delay
Mortality Rates with Primary PCI as aMortality Rates with Primary PCI as aFunction of PCI Time DelayFunction of PCI Time Delay
PP=.006=.006
Circle sizes =Circle sizes = sample size of the studysample size of the study
Solid line = weighted metaregressionSolid line = weighted metaregression
Nallamothu BK, Bates ER.Am J Cardiol. 2003;92:824-826.
62 min62 minBenefitBenefit
Favors PCIFavors PCI
HarmHarm
Favors LysisFavors Lysis
For every 10 min delay to PCI: 1% reduction in mortality difference towards lyticsFor every 10 min delay to PCI: 1% reduction in mortality difference towards lytics
55
1010
1515
00
Abs
oluteriskd
iffere
nceinde
ath(%
)
Abs
oluteriskd
iffere
nceinde
ath(%
)
5500 2020 4040 6060 8080 100100
PCI-related time delay (door to balloon - door to needle)PCI-related time delay (door to balloon - door to needle)
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Can We Improve STEMI CareCan We Improve STEMI Care
With Fibrinolysis?With Fibrinolysis?
Can We Improve STEMI CareCan We Improve STEMI CareWith Fibrinolysis?With Fibrinolysis?
Optimizing STEMI OutcomesOptimizing STEMI Outcomes
Adjunctive MedicationsAdjunctive Medications
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Adjunctive Medications Adjunctive Medications
No Effect in STEMINo Effect in STEMI
Double-bolus t-PADouble-bolus t-PA TNKTNK
rPArPA
nPAnPA
GP IIb/IIIa inhibitionGP IIb/IIIa inhibition
+lytic+lytic
Oral GP IIb/IIIaOral GP IIb/IIIa
Double-bolus t-PADouble-bolus t-PA TNKTNK
rPArPA
nPAnPA
GP IIb/IIIa inhibitionGP IIb/IIIa inhibition+lytic+lytic
Oral GP IIb/IIIaOral GP IIb/IIIa
HirudinHirudin PexulizamabPexulizamab
MagnesiumMagnesium
AdenosineAdenosine
PSGLPSGL
GIKGIK
HirudinHirudin PexulizamabPexulizamab
MagnesiumMagnesium
AdenosineAdenosine
PSGLPSGL
GIKGIK
USEFUL ADJUNCTSUSEFUL ADJUNCTS
Aspirin
Enoxaparin
Clopidogrel
USEFUL ADJUNCTSUSEFUL ADJUNCTS
Aspirin
Enoxaparin
Clopidogrel
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CLARITYTIMI 28CLARITYTIMI 28CLARITYTIMI 28CLARITYTIMI 28
Double-blind, randomized, placebo-controlled trial inDouble-blind, randomized, placebo-controlled trial in
3491 Patients, aged 183491 Patients, aged 1875 yr, with STEMI
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PlaceboClopidogrel
PP=.001=.001
Odds Ratio: 0.64Odds Ratio: 0.64(95% CI, 0.53-0.76)(95% CI, 0.53-0.76)
1.00.4 0.6 0.8 1.2 1.6
ClopidogrelBetter
PlaceboBetter
n=1752 n=1739
36%Odds Reduction
15.0
21.7
Occlude
dArter y
o
rDeath/MI
(%)
0
5
10
15
20
25
Sabatine MS, et al. N Engl J Med. 2005;352:1179-1189.
CLARITYTIMI 28CLARITYTIMI 28
CV Death MI and UrgentCV Death MI and UrgentCV Death MI and UrgentCV Death MI and Urgent
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CV Death, MI, and UrgentCV Death, MI, and Urgent
RevascularizationRevascularization
CV Death, MI, and UrgentCV Death, MI, and Urgent
RevascularizationRevascularization
Days
Endpoint(
%)
0
5
10
15
0 5 10 15 20 25 30
PlaceboPlacebo
ClopidogrelClopidogrel
Odds Ratio: 0.80Odds Ratio: 0.80
(95% CI, 0.65(95% CI, 0.650.97)0.97)
PP=.03=.03
20%20%
Sabatine MS, et al. N Engl J Med. 2005;352:1179-1189.
CLARITY TIMI 28 Bl di
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CLARITYTIMI 28: BleedingCLARITYTIMI 28: BleedingCLARITYTIMI 28: BleedingCLARITYTIMI 28: Bleeding
NSNS7.27.27.57.5In those undergoing CABGIn those undergoing CABGNSNS7.97.99.19.1CABG w/in 5 d of study medCABG w/in 5 d of study med
0.90.9
1.71.7
0.70.7
0.50.5
1.11.1
PlaceboPlacebo(%)(%)PlaceboPlacebo(%)(%)
NSNS
NSNS
NSNS
NSNS
NSNS
PPPP
1.91.9TIMI majorTIMI major
1.61.6
0.50.5
1.01.0
1.31.3
ClopidogrelClopidogrel(%)(%)ClopidogrelClopidogrel(%)(%)
TIMI minorTIMI minor
ICHICH
Through 30 daysThrough 30 days
TIMI minorTIMI minor
TIMI majorTIMI major
Through angiographyThrough angiography
OutcomeOutcomeOutcomeOutcome
Sabatine MS, et al. N Engl J Med. 2005;352:1179-1189.
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STEMI < 6 hoursSTEMI < 6 hours
Lytic eligibleLytic eligibleLytic choice by MDLytic choice by MD
(TNK, tPA, rPA, SK)(TNK, tPA, rPA, SK)
ENOXAPARIN< 75 y: 30 mg IV bolus
SC 1.0 mg / kg q 12 h (Hosp DC)
75 y: No bolus
SC 0.75 mg / kg q 12 h (Hosp DC)
CrCl < 30: 1.0 mg / kg q 24h
Double-blind, double-dummyDouble-blind, double-dummy
ASAASA
Day 30Day 30
11 Efficacy Endpoint: Death or Nonfatal MIEfficacy Endpoint: Death or Nonfatal MI
1 Safety Endpoint: TIMI Major Hemorrhage1 Safety Endpoint: TIMI Major Hemorrhage
EXTRACT: TIMI 25EXTRACT: TIMI 25EXTRACT: TIMI 25EXTRACT: TIMI 25
UFH60 U / kg bolus (4000 U)
Inf 12 U / kg / h (1000 U / h)
Duration: at least 48 h
Contd at MD discretion
Primary End Point (ITT) Primary End Point (ITT) Primary End Point (ITT) Primary End Point (ITT)
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Primary End Point (ITT) Primary End Point (ITT) Death or Nonfatal MIDeath or Nonfatal MI
Primary End Point (ITT) Primary End Point (ITT) Death or Nonfatal MIDeath or Nonfatal MI
0
3
6
9
12
15
0 5 10 15 20 25 30
P
rimaryEnd
Point( %
)
P
rimar y
EndPoint( %
)
ENOX
UFH
Relative RiskRelative Risk
0.83 (0.77 to 0.90)0.83 (0.77 to 0.90)
P
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Death or Nonfatal MI Day 30Death or Nonfatal MI Day 30
Medical Therapy vs Any PCIMedical Therapy vs Any PCIDeath or Nonfatal MI Day 30Death or Nonfatal MI Day 30
Medical Therapy vs Any PCIMedical Therapy vs Any PCI
0.00040.00040.0010.001
%%
Event
s
Event s
0
5
10
15
Any PCI Medical RxN = 15,223 (75%)N = 4,676 (23%)
P ValueP Value
9.79.7
RRRRRR
16%16%
11.411.413.813.8
10.710.7
RRRRRR
23%23%
EnoxaparinEnoxaparin
UFHUFH
EnoxaparinEnoxaparin
UFHUFH
Antman EM, et al.Antman EM, et al. NEJMNEJM354:1477-1488354:1477-1488Antman EM, et al.Antman EM, et al. NEJMNEJM354:1477-1488354:1477-1488
Death or Nonfatal MI Day 30Death or Nonfatal MI Day 30Death or Nonfatal MI Day 30Death or Nonfatal MI Day 30
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Death or Nonfatal MI Day 30Death or Nonfatal MI Day 30
Clopidogrel UseClopidogrel Use
Death or Nonfatal MI Day 30Death or Nonfatal MI Day 30Clopidogrel UseClopidogrel Use
0.00050.0005 0.00060.0006
%%
Event s
Event s
0
5
10
15
No Clopidogrel Clopidogrel Use*N = 14,752 (78%) N = 5,727 (28%)
P ValueP Value
10.410.4
RRRRRR
15%15%
12.212.211.411.4
8.78.7
RRRRRR
24%24%
* 2546 clopidogrel treated patients did not undergo PCI
EnoxaparinEnoxaparin
UFHUFH
EnoxaparinEnoxaparin
UFHUFH
Antman EM, et al.Antman EM, et al. NEJMNEJM354:1477-1488354:1477-1488Antman EM, et al.Antman EM, et al. NEJMNEJM354:1477-1488354:1477-1488
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Net Clinical Benefit at 30 DaysNet Clinical Benefit at 30 DaysNet Clinical Benefit at 30 DaysNet Clinical Benefit at 30 Days
11 1.251.250.90.90.80.8
Death or Nonfatal MI orDeath or Nonfatal MI or
Nonfatal ICHNonfatal ICH
Death or Nonfatal MI orDeath or Nonfatal MI or
Nonfatal Major BleedNonfatal Major Bleed
Death or Nonfatal MI orDeath or Nonfatal MI or
Nonfatal Disabl. StrokeNonfatal Disabl. Stroke
ENOX BetterENOX Better UFH BetterUFH BetterRRRR
UFH (%)UFH (%) ENOX (%)ENOX (%) RRR (%RRR (%
12.312.3 10.110.1 1818
12.812.8 11.011.0 1414
12.212.2 10.110.1 1717
Prespecified DefinitionsPrespecified Definitions
P
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ppPCI vs Lysis for STEMIPCI vs Lysis for STEMI
7
2.2
3.4
0
2
4
6
8
10
%
Eve
nts
%
Eve
nts
(30-42
Days)
(30-42Days)
ReinfarctionReinfarction
Lytic
Arms
(UFH) PCI
ArmsENOX
Overview of 23 RCTsOverview of 23 RCTsOverview of 23 RCTsOverview of 23 RCTs
The advance in adjunctive therapy with enoxaparin has narrowed the gapThe advance in adjunctive therapy with enoxaparin has narrowed the gap
between PCI and Lysis as reperfusion for STEMIbetween PCI and Lysis as reperfusion for STEMIThe advance in adjunctive therapy with enoxaparin has narrowed the gapThe advance in adjunctive therapy with enoxaparin has narrowed the gap
between PCI and Lysis as reperfusion for STEMIbetween PCI and Lysis as reperfusion for STEMI
Keeley EC, Boura JA, Grines CL. Lancet. 2003.
Study Design: Randomized, Double Blind,Study Design: Randomized, Double Blind,
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12,000 Patients with STEMI < 12 h of symptom onset
Inclusion: ST 2 mm prec leads or 1 mm limb leadsExclusion: Contraindicated. For anticoagulant, INR > 1.8, pregnancy, ICH
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y yy yDeath/MI at 30 DaysDeath/MI at 30 Days
DaysDays
C
umu
lative
H
azard
C
umu
lative H
azard
0.0
0.0
0.0
2
0.0
2
0.04
0.04
0.06
0.06
0.08
0.08
0.10
0.10
0.12
0.12
00 33 66 99 1212 1515 1818 2121 2424 2727 3030
UFH/PlaceboUFH/Placebo
FondaparinuxFondaparinux
HR 0.86HR 0.86
95% CI 0.77-95% CI 0.77-0.960.96
P=0.008P=0.008
Keeley EC, Boura JA, Grines CL. Lancet. 2003.
Efficacy of Fondaparinux by StrataEfficacy of Fondaparinux by Strata
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y p yy p yon Death/MIon Death/MI
0.760.76--1.021.020.880.8811.211.212.712.7Stratum II (n = 6434)Stratum II (n = 6434)
(Fonda vs. UFH)(Fonda vs. UFH)
0.760.76
--0.990.99
0.870.87
15.915.9
17.317.3
Stratum I (n = 5658)Stratum I (n = 5658)
(Fonda vs. Placebo)(Fonda vs. Placebo)
95% CI95% CIHRHRFondaFondaControlControl
No. of Events (%)No. of Events (%)
Interaction P=0.88Interaction P=0.88
Keeley EC, Boura JA, Grines CL. Lancet. 2003.
STEMI C l iSTEMI C l i
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STEMI ConclusionsSTEMI Conclusions
There is still a role for fibrinolyticThere is still a role for fibrinolytictherapy in STEMItherapy in STEMI
Adjuvant clopidogrel and/orAdjuvant clopidogrel and/or
enoxaparin improve outcomes inenoxaparin improve outcomes incombination with fibrinolyticscombination with fibrinolytics
Fondaparinux improves outcomesFondaparinux improves outcomesrelative to placeborelative to placebo
G tti i th (U ) St f ThiGetting in the (Up) Stream of Things
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ACS: Recent Clinical Trials in
STEMI and NSTEMI
ACS: Recent Clinical Trials in
STEMI and NSTEMI
Getting in the (Up) Stream of ThingsGetting in the (Up) Stream of Things
The Link Between GuidelineThe Link Between GuidelineThe Link Between GuidelineThe Link Between Guideline
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5.955.956.336.33
5.165.16 5.075.07 4.974.974.634.63
4.164.16 4.174.17
0
1
22
33
44
55
66
7
Hospital Composite Quality Quartiles
%
In-hosp
italMo
rtality
Every 10%Every 10% in guidelines adherence =in guidelines adherence =11%11% in mortality (OR=0.89, 95% CI, 0.81-0.98)in mortality (OR=0.89, 95% CI, 0.81-0.98)
Peterson ED et al. J Am Coll Cardiol. 2004;43(suppl A):406A. Abstract 1077-71.
Implementation and Mortality Is ClearImplementation and Mortality Is ClearImplementation and Mortality Is ClearImplementation and Mortality Is Clear
25% 25%50% 50%75% 75%
Adjusted
UnadjustedUnadjusted
Antithrombotic and AntiplateletAntithrombotic and AntiplateletAntithrombotic and AntiplateletAntithrombotic and Antiplatelet
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pp
Therapy in ACSTherapy in ACSpp
Therapy in ACSTherapy in ACS
ACC/AHA Guideline Update for UA and NSTEMI. 2002.
CURE:CURE: CClopidogrel inlopidogrel in UUnstable Angina tonstable Angina to
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PreventPrevent RRecurrentecurrent EEventsvents
CURE: Primary End Point:CURE: Primary End Point:
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yy
MI/Stroke/CV Death (N=12,562*)MI/Stroke/CV Death (N=12,562*)
CURE S f tCURE S f tCURE S f tCURE S f t
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CURE SafetyCURE SafetyCURE SafetyCURE Safety
SYNERGY D iSYNERGY Design
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SYNERGY DesignSYNERGY Design
At least 2 of 3 required:
Age 60 ST (transient) or
(+) CK-MB or troponin
Primary endpoint: Death or MI at 30 days
High-riskHigh-risk
ACS PatientsACS Patients
Early invasive strategyOther therapy per ACC/AHA guidelines
(ASA, -blocker, ACE, clopidogrel, GP IIb/IIIa)
Enoxaparin IV UFH
RandomizeRandomize
(n = 10,000)(n = 10,000)
60 U/kg60 U/kg 12 U/kg/h12 U/kg/h(aPTT 50 70 sec)(aPTT 50 70 sec)1 mg/kg SC Q12 h
1 mg/kg SC Q12 h
SYNERGY Trial Investigators. JAMA 2004;292:45-54SYNERGY Trial Investigators. JAMA 2004;292:45-54
D th d MI t 30 DD th d MI t 30 DD th d MI t 30 DD th d MI t 30 D
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Death and MI at 30 DaysDeath and MI at 30 DaysDeath and MI at 30 DaysDeath and MI at 30 Days
1
Hazard Ratio (95% CI)
Enoxaparin UFH
Better Better
30-day Death/MI30-day Death/MI
0.8 1.0
1.2
HR 0.96 (0.86
1.06)
HR 0.96 (0.86
1.06)
1.11.1
0 5 10 15 20 25 300.8
0.9
0.95
1.0
Freedo
m
fromD
eat h
/MI
Days from Randomization
0.85Enoxaparin
UFH
Enoxaparin
UFH
SYNERGY Trial Investigators. JAMA 2004;292:45-54SYNERGY Trial Investigators. JAMA 2004;292:45-54
6-Month Survival Death/MI6-Month Survival Death/MI
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(Intention-to-Treat)(Intention-to-Treat)
HR (95% CI) = 0.978 (0.891, 1.075)HR (95% CI) = 0.978 (0.891, 1.075)
0 3030 6060 9090 120120 150150 1801800.7
0.750.75
0.80.8
0.850.85
0.90.9
0.950.95
1
Freedo
m
from
De a
th/M
Iat6M
on
ths
Days from Randomization
UFHUFH
EnoxaparinEnoxaparin
SYNERGY Trial Investigators. JAMA 2004;292:45-54SYNERGY Trial Investigators. JAMA 2004;292:45-54
Bl di E tBl di E tBl di E tBleeding Events
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Bleeding EventsBleeding EventsBleeding EventsBleeding Events
GUSTO severe 2.7 2.2 0.08
TIMI major (clinical): 9.1 7.6 0.008
CABG-related 6.8 5.9 0.08Non-CABG-related 2.4 1.8 0.03
Hb/HCT drop (algorithm) 15.2 12.5 < 0.001
Any RBC transfusion 17.0 16.0 0.16
ICH < 0.1 < 0.1 NS
EnoxaparinEnoxaparin UFHUFH P valueP value(n = 4,993)(n = 4,993) (n = 4,985)(n = 4,985)
%%
SYNERGY Trial Investigators. JAMA 2004;292:45-54SYNERGY Trial Investigators. JAMA 2004;292:45-54
SYNERGY C l i /C tSYNERGY C l i /C t
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Enoxaparin was not superior to unfractionated heparinEnoxaparin was not superior to unfractionated heparinbut was noninferior for nonST-segment elevation ACSbut was noninferior for nonST-segment elevation ACS
More bleeding was observed with enoxaparinMore bleeding was observed with enoxaparin
Enoxaparin was an alternative to unfractionatedEnoxaparin was an alternative to unfractionatedheparin for nonST-segment elevation ACS in high-riskheparin for nonST-segment elevation ACS in high-risk
patients being managed with a rapid transition topatients being managed with a rapid transition tointerventionintervention
Do not change fromDo not change fromq UFH to Enoxaparin, orUFH to Enoxaparin, or
q Enoxaparin to UFHEnoxaparin to UFH Stay with the agent initiated in the EDStay with the agent initiated in the ED
q CollaborationCollaboration
q PathwaysPathways
q Bivalirudin may be exceptionBivalirudin may be exception
SYNERGY: Conclusions/CaveatsSYNERGY: Conclusions/Caveats
OASIS 5 St d D iOASIS 5 Study DesignOASIS 5 Study DesignOASIS 5 Study Design
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OASIS-5 Study DesignOASIS-5 Study DesignOASIS-5 Study DesignOASIS-5 Study Design
Yusuf S, et al. N Engl J Med. 2006;354(14):1464-76Yusuf S, et al. N Engl J Med. 2006;354(14):1464-76
Patients w/ NSTE ACSPatients w/ NSTE ACS Chest pain < 24 hours2/3:
Age > 60ST-segment
cardiac markers
Chest pain < 24 hours
2/3:
Age > 60ST-segment
cardiac markers
ASA, clopidogrel, IIb/IIIa,
planned cath per local
practice
ASA, clopidogrel, IIb/IIIa,
planned cath per local
practice
Exclude
Age < 21
Contraindication to enoxHemorrhagic stroke < 12 mo
Creat > 3 mg/dL (265 umol/L)
Exclude
Age < 21
Contraindication to enoxHemorrhagic stroke < 12 mo
Creat > 3 mg/dL (265 umol/L)
RandomizeRandomize
n = 20,000n = 20,000
Fondaparinux
2.5 mg sc qd
Fondaparinux2.5 mg sc qd
Enoxaparin
1 mg/kg sc bid
Enoxaparin1 mg/kg sc bid
PCI < 6 h: IV fondaparinux2.5 mg w/o IIb/IIIa, 0 w/ IIb/IIIa
PCI > 6h: IV fondaparinux
5 mg w/o IIb/IIIa, 2.5 mg w/ IIb/IIIa
PCI < 6 h: IV fondaparinux2.5 mg w/o IIb/IIIa, 0 w/ IIb/IIIa
PCI > 6h: IV fondaparinux
5 mg w/o IIb/IIIa, 2.5 mg w/ IIb/IIIa
Primary Efficacy: Death, MI, refractory ischemia at 9 daysSafety: Major bleeding at 9 days
Risk/Benefit: Death, MI, refractory ischemia and major bleeding at 9 days
Secondary Above and each component separately at day 30 and 6 months
Primary Efficacy: Death, MI, refractory ischemia at 9 daysSafety: Major bleeding at 9 days
Risk/Benefit: Death, MI, refractory ischemia and major bleeding at 9 days
Secondary Above and each component separately at day 30 and 6 months
PCI < 6 h: no UFH
PCI > 6h: IV UFH
100 U/kg w/o IIb/IIIa
60 U/kg w/ IIb/IIIa
PCI < 6 h: no UFH
PCI > 6h: IV UFH
100 U/kg w/o IIb/IIIa
60 U/kg w/ IIb/IIIaOutcomesOutcomes
OASIS 5: Efficacy at Day 9OASIS 5: Efficacy at Day 9
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OASIS5: Efficacy at Day 9OASIS5: Efficacy at Day 9EnoxEnox FondaFonda
%%
Death/MI/RIDeath/MI/RI 5.85.8 5.95.9
Death/MIDeath/MI 4.14.1 4.14.1
DeathDeath 1.91.9 1.81.8
MIMI 2.72.7 2.72.7
Refract IschRefract Isch 1.91.9 2.052.05
0.80.8 11 1.21.2
Non-inferiorityNon-inferiority
Margin = 1.185Margin = 1.185
Hazard RatioHazard Ratio
Fonda BetterFonda Better Enox BetterEnox Better
Yusuf S, et al. N Engl J Med. 2006;354(14):1464-76Yusuf S, et al. N Engl J Med. 2006;354(14):1464-76
OASIS 5 Bl di R t t D 9OASIS 5: Bleeding Rates at Day 9OASIS 5: Bleeding Rates at Day 9OASIS 5: Bleeding Rates at Day 9
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OASIS5: Bleeding Rates at Day 9OASIS5: Bleeding Rates at Day 9OASIS5: Bleeding Rates at Day 9OASIS5: Bleeding Rates at Day 9
OutcomeOutcome EnoxEnox FondaFonda HR (95% CI)HR (95% CI) PP
No. RandomizedNo. Randomized 10,02110,021 10,05710,057
Total Bleed (%)Total Bleed (%) 7.07.0 3.23.2 0.44 (0.39 0.51)0.44 (0.39 0.51) < 0.0001< 0.0001
Major Bleed (%)Major Bleed (%) 4.04.0 2.12.1 0.53 (0.45 0.62)0.53 (0.45 0.62) < 0.0001< 0.0001
TIMI Major Bleed (%)TIMI Major Bleed (%) 1.31.3 0.70.7 0.54 (0.41 0.73)0.54 (0.41 0.73) < 0.0001< 0.0001
Minor Bleed (%)Minor Bleed (%) 3.13.1 1.11.1 0.35 (0.28 0.43)0.35 (0.28 0.43) < 0.0001< 0.0001
Yusuf S, et al. N Engl J Med. 2006;354(14):1464-76Yusuf S, et al. N Engl J Med. 2006;354(14):1464-76
Efficacy End Points at 6 MonthsEfficacy End Points at 6 Months
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Efficacy End Points at 6 MonthsEfficacy End Points at 6 Months
End pointEnd point EnoxaparinEnoxaparin FondaparinuxFondaparinux P valueP value
Death/MI/ refractory ischemiaDeath/MI/ refractory ischemia 13.2%13.2% 12.3%12.3% 0.060.06
Death/MIDeath/MI 11.4%11.4% 10.5%10.5% 0.050.05
DeathDeath 6.5%6.5% 5.8%5.8% 0.050.05
MIMI 6.6%6.6% 6.3%6.3% NSNS
StrokeStroke 1.7%1.7% 1.3%1.3% 0.040.04
Death/MI/stroke*Death/MI/stroke* 12.5%12.5% 11.3%11.3% 0.0070.007
Yusuf S, et al. N Engl J Med. 2006;354(14):1464-76Yusuf S, et al. N Engl J Med. 2006;354(14):1464-76
PCI Procedural ComplicationsPCI Procedural ComplicationsPCI Procedural ComplicationsPCI Procedural Complications
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PCI Procedural ComplicationsPCI Procedural ComplicationsPCI Procedural ComplicationsPCI Procedural Complications
Events (30 Days)Events (30 Days) EnoxaparinEnoxaparin
n=3089n=3089
FondaparinuxFondaparinux
n=3118n=3118
P valueP value
Any UFH during PCIAny UFH during PCI 53.8%53.8% 18.8%18.8%
Any proceduralAny proceduralcomplicationcomplication
8.6%8.6% 9.6%9.6% 0.180.18
Abrupt closureAbrupt closure 1.1%1.1% 1.5%1.5% 0.200.20
Catheter thrombusCatheter thrombus 0.5%0.5% 1.3%1.3% 0.0010.001
Vascular accessVascular access 8.1%8.1% 3.3%3.3%
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Moderate-
high risk
ACS
First RandomizationFirst Randomization
Moderate-high risk unstable angina or NSTEMIundergoing an invasive strategy (N = 13,819)
Moderate-high risk unstable angina or NSTEMIundergoing an invasive strategy (N = 13,819)
Ang
iog
raphywithin
72h
Aspirin in allAspirin in allClopidogrelClopidogrel
dosing and timingdosing and timing
per local practiceper local practice
UFH orEnoxaparin+ GP IIb/IIIa
Bivalirudin+ GP IIb/IIIa
BivalirudinAlone
R*
ACUITY Design. Stone GW et al. AHJ 2004;148:76475
Medical
management
PCI
CABG
Primary endpoint: Net Clinical Composite
Death, MI, TVR, Bleeding
Primary endpoint: Net Clinical Composite
Death, MI, TVR, Bleeding
ACUITY Study Design S d R d i tiACUITY Study Design S d R d i ti
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Moderate-
high risk
ACS
Second RandomizationSecond Randomization
Moderate-high risk unstable angina or NSTEMIundergoing an invasive strategy (N = 13,819)
Moderate-high risk unstable angina or NSTEMIundergoing an invasive strategy (N = 13,819)
Ang
iog
raphywithin
72h
ACUITY Design. Stone GW et al. AHJ 2004;148:76475
Aspirin in allClopidogrel
dosing and timing
per local practice
Medical
management
PCI
CABG
BivalirudinAlone
UFH or Enoxaparin
Routine upstream
GPI in all pts
GPI started in CCL
for PCI only
R
Bivalirudin
R
Routine upstream
GPI in all pts
GPI started in CCL
for PCI only
3 Primary Endpoints (at 30 Days)3 Primary Endpoints (at 30 Days)
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1. Composite net clinical benefit =
2. Ischemic composite
or
3. Major bleeding
3 Primary Endpoints (at 30 Days)y p ( y )
Death from any cause
Myocardial infarction- During medical Rx: Any biomarker elevation >ULN- Post PCI: CKMB >ULN with new Q waves or >3x ULN w/o Q waves
- Post CABG: CKMB >5x ULN with new Q waves, >10x ULN w/o Q waves
Unplanned revascularization for ischemia
Stone GW, McLaurin BT. NEJM. 2006 Nov 23;355(21):2203-16.Stone GW, McLaurin BT. NEJM. 2006 Nov 23;355(21):2203-16.
3 Primary Endpoints (at 30 Days)3 Primary Endpoints (at 30 Days)
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1. Composite net clinical benefit =
2. Ischemic composite
or
3. Major bleeding
3 Primary Endpoints (at 30 Days)3 Primary Endpoints (at 30 Days)
Non CABG related bleeding
Intracranial bleeding or intraocular bleedingIntracranial bleeding or intraocular bleeding
Retroperitoneal bleedingRetroperitoneal bleeding
Access site bleed requiring intervention/surgeryAccess site bleed requiring intervention/surgery
Hematoma 5 cmHematoma 5 cm
HgbHgb 3g/dL with an overt source or3g/dL with an overt source or4g/dL w/o overt source4g/dL w/o overt source
Blood product transfusionBlood product transfusion
-- Reoperation for bleedingReoperation for bleeding
Stone GW, McLaurin BT. NEJM. 2006 Nov 23;355(21):2203-16.Stone GW, McLaurin BT. NEJM. 2006 Nov 23;355(21):2203-16.
Ischemic Composite EndpointIschemic Composite EndpointIschemic Composite EndpointIschemic Composite Endpoint
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Ischemic Composite EndpointIschemic Composite EndpointIschemic Composite EndpointIschemic Composite Endpoint
0
5
10
15
0 5 10 15 20 25 30 35
CumulativeEv
ents(%)
Days from Randomization
EstimateEstimate PP
(log rank)(log rank)7.3%7.3%UFH/Enoxaparin + IIb/IIIa (N=4603)UFH/Enoxaparin + IIb/IIIa (N=4603)
Bivalirudin + IIb/IIIa (N=4604)Bivalirudin + IIb/IIIa (N=4604) 0.370.377.7%7.7%
Bivalirudin alone (N=4612)Bivalirudin alone (N=4612) 0.300.307.8%7.8%
Stone GW, McLaurin BT. NEJM. 2006 Nov 23;355(21):2203-16.Stone GW, McLaurin BT. NEJM. 2006 Nov 23;355(21):2203-16.
Major Bleeding EndpointMajor Bleeding EndpointMajor Bleeding EndpointMajor Bleeding Endpoint
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Major Bleeding EndpointMajor Bleeding EndpointMajor Bleeding EndpointMajor Bleeding Endpoint
0
5
10
15
0 5 10 15 20 25 30 35
CumulativeEv
ents(%)
Days from Randomization
EstimateEstimate PP
(log rank)(log rank)5.7%5.7%UFH/Enoxaparin + IIb/IIIa (N=4603)UFH/Enoxaparin + IIb/IIIa (N=4603)
Bivalirudin + IIb/IIIa (N=4604)Bivalirudin + IIb/IIIa (N=4604) 0.410.415.3%5.3%
Bivalirudin alone (N=4612)Bivalirudin alone (N=4612)
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Net Clinical OutcomeNet Clinical OutcomeNet Clinical OutcomeNet Clinical Outcome
0
5
10
15
0 5 10 15 20 25 30 35
Cumula
tiveEvents(%
)
Days from Randomization
EstimateEstimate PP
(log rank)(log rank)11.7%11.7%UFH/Enoxaparin + IIb/IIIa (N=4603)UFH/Enoxaparin + IIb/IIIa (N=4603)
Bivalirudin + IIb/IIIa (N=4604)Bivalirudin + IIb/IIIa (N=4604) 0.890.8911.8%11.8%
Bivalirudin alone (N=4612)Bivalirudin alone (N=4612) 0.0140.01410.1%10.1%
Stone GW, McLaurin BT. NEJM. 2006 Nov 23;355(21):2203-16.Stone GW, McLaurin BT. NEJM. 2006 Nov 23;355(21):2203-16.
ACUITY Mortality at 1 yearACUITY Mortality at 1 yearACUITY Mortality at 1-yearACUITY Mortality at 1-year
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0 30 60 90 120 150 180 210 240 270 300 330 360 3900
4
5
Mortalit
y(%)
Days from Randomization
2
1
ACUITY Mortality at 1-yearACUITY Mortality at 1-yearACUITY Mortality at 1-yearACUITY Mortality at 1-year
UFH/Enoxaparin + IIb/IIIa
Bivalirudin + IIb/IIIa
Bivalirudin alone
Estimate
P(log rank)
1.4%
0.531.6%
0.391.6%
Estimate
P(log rank)
4.4%
0.934.2%
0.663.8%
1 year
p=0.90
Bivalirudin+GPI vs. Hep+GPI
HR [95% CI] = 0.99 (0.80-1.22)
30 day
3
Bivalirudin alone vs. Hep+GPI
HR [95% CI] = 0.95 (0.77-1.18)
Stone GW, McLaurin BT. NEJM. 2006 Nov 23;355(21):2203-16.Stone GW, McLaurin BT. NEJM. 2006 Nov 23;355(21):2203-16.
ACUITY ConclusionsACUITY ConclusionsACUITY ConclusionsACUITY Conclusions
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Bivalirudin plus IIb/IIIa had similar ischemicBivalirudin plus IIb/IIIa had similar ischemicoutcomes, similar bleeding, and similar netoutcomes, similar bleeding, and similar net
clinical benefit to heparin plus IIb/IIIaclinical benefit to heparin plus IIb/IIIa
Bivalirudin alone (with provisional IIb/IIIa use)Bivalirudin alone (with provisional IIb/IIIa use)had similar ischemic outcomes, less bleeding,had similar ischemic outcomes, less bleeding,
and superior net clinical benefit to heparin plusand superior net clinical benefit to heparin plus
IIb/IIIaIIb/IIIa
Whether or not reductions in bleeding willWhether or not reductions in bleeding will
translate into longer-term reductions in mortalitytranslate into longer-term reductions in mortality
is yet to be determinedis yet to be determined
Bivalirudin plus IIb/IIIa had similar ischemicBivalirudin plus IIb/IIIa had similar ischemicoutcomes, similar bleeding, and similar netoutcomes, similar bleeding, and similar net
clinical benefit to heparin plus IIb/IIIaclinical benefit to heparin plus IIb/IIIa
Bivalirudin alone (with provisional IIb/IIIa use)Bivalirudin alone (with provisional IIb/IIIa use)had similar ischemic outcomes, less bleeding,had similar ischemic outcomes, less bleeding,
and superior net clinical benefit to heparin plusand superior net clinical benefit to heparin plus
IIb/IIIaIIb/IIIa
Whether or not reductions in bleeding willWhether or not reductions in bleeding will
translate into longer-term reductions in mortalitytranslate into longer-term reductions in mortality
is yet to be determinedis yet to be determined
ACUITY ConclusionsACUITY ConclusionsACUITY ConclusionsACUITY Conclusions
NSTEMI ConclusionsNSTEMI ConclusionsNSTEMI ConclusionsNSTEMI Conclusions
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NSTEMI ConclusionsNSTEMI ConclusionsNSTEMI ConclusionsNSTEMI Conclusions
Old and new options for ACSOld and new options for ACSq UFH or EnoxaparinUFH or Enoxaparinq BivalirudinBivalirudinq Fondaparinux (not tested adequately in cath lab)Fondaparinux (not tested adequately in cath lab)
Balance ischemic efficacy and safetyBalance ischemic efficacy and safetyq Customize approach for patient and institutionCustomize approach for patient and institution
Many choicesMany choicesq
Collaborate with IC and CARD on clinical pathwaysCollaborate with IC and CARD on clinical pathways
Adapt ACC/AHA 2007 Guidelines to ClinicalAdapt ACC/AHA 2007 Guidelines to ClinicalPractice in ED (Endorsed by SAEM)Practice in ED (Endorsed by SAEM)
Old and new options for ACSOld and new options for ACSq UFH or EnoxaparinUFH or Enoxaparinq BivalirudinBivalirudinq Fondaparinux (not tested adequately in cath lab)Fondaparinux (not tested adequately in cath lab)
Balance ischemic efficacy and safetyBalance ischemic efficacy and safetyq Customize approach for patient and institutionCustomize approach for patient and institution
Many choicesMany choicesq Collaborate with IC and CARD on clinical pathwaysCollaborate with IC and CARD on clinical pathways
Adapt ACC/AHA 2007 Guidelines to ClinicalAdapt ACC/AHA 2007 Guidelines to ClinicalPractice in ED (Endorsed by SAEM)Practice in ED (Endorsed by SAEM)
Getting in the (Up)Stream of ThingsGetting in the (Up)Stream of ThingsGetting in the (Up)Stream of ThingsGetting in the (Up)Stream of Things
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Acute Coronary SyndromeAcute Coronary SyndromeThe 2007 ACC/AHA UA/NSTEMI Guidelines The 2007 ACC/AHA UA/NSTEMI Guidelines
From the ED to the CCU and Cath LabFrom the ED to the CCU and Cath Lab
Adherence as the Road to Better OutcomesAdherence as the Road to Better Outcomes
Acute Coronary SyndromeAcute Coronary SyndromeThe 2007 ACC/AHA UA/NSTEMI Guidelines The 2007 ACC/AHA UA/NSTEMI Guidelines From the ED to the CCU and Cath LabFrom the ED to the CCU and Cath Lab
Adherence as the Road to Better OutcomesAdherence as the Road to Better Outcomes
Getting in the (Up)Stream of ThingsGetting in the (Up)Stream of ThingsGetting in the (Up)Stream of ThingsGetting in the (Up)Stream of Things
Charles V. Pollack Jr, MA, MD, FACEP, FAAEMCharles V. Pollack Jr, MA, MD, FACEP, FAAEMChairman, Department of Emergency MedicineChairman, Department of Emergency Medicine
Pennsylvania HospitalPennsylvania HospitalProfessor of Emergency MedicineProfessor of Emergency Medicine
University of PennsylvaniaUniversity of Pennsylvania
School of MedicineSchool of Medicine
Philadelphia, PennsylvaniaPhiladelphia, Pennsylvania
Charles V. Pollack Jr, MA, MD, FACEP, FAAEMCharles V. Pollack Jr, MA, MD, FACEP, FAAEMChairman, Department of Emergency MedicineChairman, Department of Emergency Medicine
Pennsylvania HospitalPennsylvania HospitalProfessor of Emergency MedicineProfessor of Emergency Medicine
University of PennsylvaniaUniversity of Pennsylvania
School of MedicineSchool of Medicine
Philadelphia, PennsylvaniaPhiladelphia, Pennsylvania
Evolution of Guidelines for ACSEvolution of Guidelines for ACSEvolution of Guidelines for ACSEvolution of Guidelines for ACS
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19901990
19921992
19941994
19961996
19981998
20002000
20022002
19901990
ACC/AHAACC/AHA
AMIAMI
R. GunnarR. Gunnar
19941994
AHCPR/NHLBIAHCPR/NHLBI
UAUA
E. BraunwaldE. Braunwald19961996 19991999
RevisedRevised UpdatedUpdated
ACC/AHA AMIACC/AHA AMIT. RyanT. Ryan
2004 20072004 2007
Revised UpdatedRevised UpdatedACC/AHA STEMIACC/AHA STEMI
E. AntmanE. Antman
2004 20072004 2007
Revised UpdatedRevised UpdatedACC/AHA STEMIACC/AHA STEMI
E. AntmanE. Antman
2000 20022000 2002 20072007
Revised UpdatedRevised Updated RevisedRevised
ACC/AHA UA/NSTEMIACC/AHA UA/NSTEMI
E. Braunwald J. AndersonE. Braunwald J. Anderson
2000 20022000 2002 20072007
Revised UpdatedRevised Updated RevisedRevised
ACC/AHA UA/NSTEMIACC/AHA UA/NSTEMI
E. Braunwald J. AndersonE. Braunwald J. Anderson
20042004 20072007
Sea and Stream Changes in ACSSea and Stream Changes in ACSSea and Stream Changes in ACSSea and Stream Changes in ACS
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Sea and Stream Changes in ACSSea and Stream Changes in ACSSea and Stream Changes in ACSSea and Stream Changes in ACS
The 2007 Guidelines have created a SeaThe 2007 Guidelines have created a SeaChange in theChange in the EDED andand ICIC TTherapeuticherapeuticapproach to care of patients with UA/NSTEMIapproach to care of patients with UA/NSTEMI
New Streams of care, with newNew Streams of care, with new
anticoagulants, are in playanticoagulants, are in play Clopidogrel use has been liberalizedClopidogrel use has been liberalized Bleeding end points play a more importantBleeding end points play a more important
role in drug selectionrole in drug selection
Dogmatism is out, customization is inDogmatism is out, customization is in Collaboration is emphasizedCollaboration is emphasized
Applying Classification ofApplying Classification of
R d tiR d ti
Applying Classification ofApplying Classification of
R d tiR d ti
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Class I
Benefit >>> Risk
Procedure/ TreatmentSHOULD be performed/administered
Class IIa
Benefit >> RiskAdditional studies withfocused objectivesneeded
IT IS REASONABLE toperformprocedure/administer
treatment
Class IIb
Benefit RiskAdditional studies withbroad objectives needed;Additional registry datawould be helpful
Procedure/TreatmentMAY BE CONSIDERED
Class III
Risk BenefitNo additional studiesneeded
Procedure/Treatmentshould NOT beperformed/administeredSINCE IT IS NOT
HELPFUL AND MAY BEHARMFUL
ShouldShouldIs recommendedIs recommendedIs indicatedIs indicated
Is useful/effective/Is useful/effective/beneficialbeneficial
Is reasonableIs reasonableCan be useful/effective/Can be useful/effective/
beneficialbeneficial
Is probably recommendedIs probably recommendedor indicatedor indicated
May/might be consideredMay/might be consideredMay/might be reasonableMay/might be reasonableUsefulness/Usefulness/
effectiveness iseffectiveness isunknown/unclear/unknown/unclear/uncertain or not welluncertain or not wellestablishedestablished
Is not recommendedIs not recommende