2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary

90 Pages·2014·4.27 MB·English

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 64, NO. 24, 2014
ª2014 BY THE AMERICAN HEART ASSOCIATION, INC., ISSN 0735-1097/$36.00
AND THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION http://dx.doi.org/10.1016/j.jacc.2014.09.017
PUBLISHED BY ELSEVIER INC.
CLINICAL PRACTICE GUIDELINE
2014 AHA/ACC Guideline for
the Management of Patients
–
With Non ST-Elevation Acute
Coronary Syndromes
AReportoftheAmericanCollegeofCardiology/AmericanHeartAssociation
TaskForceonPracticeGuidelines
DevelopedinCollaborationWiththeSocietyforCardiovascularAngiographyandInterventions
andSocietyofThoracicSurgeons
EndorsedbytheAmericanAssociationforClinicalChemistry
Writing EzraA.Amsterdam,MD,FACC,Chairy EricD.Peterson,MD,MPH,FACC,FAHA*#
Committee NanetteK.Wenger,MD,MACC,FAHA,ViceChair*y MarcS.Sabatine,MD,MPH,FACC,FAHA*y
Members* RichardW.Smalling,MD,PHD,FACC,FSCAI***
RalphG.Brindis,MD,MPH,MACC,FSCAIz SusanJ.Zieman,MD,PHD,FACCy
DonaldE.CaseyJR,MD,MPH,MBA,FACP,FAHAx
TheodoreG.Ganiats,MDjj
DavidR.HolmesJR,MD,MACCy *Writingcommitteemembersarerequiredtorecusethemselvesfrom
AllanS.Jaffe,MD,FACC,FAHA*y votingonsectionstowhichtheirspecificrelationshipswithindustry
andotherentitiesmayapply;seeAppendix1forrecusalinformation.
HaniJneid,MD,FACC,FAHA,FSCAIy yACC/AHARepresentative.zACC/AHATaskForceonPracticeGuidelines
RosemaryF.Kelly,MD{ Liaison.xAmericanCollegeofPhysiciansRepresentative.kAmerican
MichaelC.Kontos,MD,FACC,FAHA*y AcademyofFamilyPhysiciansRepresentative.{SocietyofThoracic
SurgeonsRepresentative.#ACC/AHATaskForceonPerformance
GlennN.Levine,MD,FACC,FAHAy
MeasuresLiaison.**SocietyforCardiovascularAngiographyand
PhilipR.Liebson,MD,FACC,FAHAy InterventionsRepresentative.
DebabrataMukherjee,MD,FACCy
ThewritingcommitteegratefullyacknowledgesthememoryofDr.FrancisM.Fesmire(representativeoftheAmericanCollegeofEmergencyPhy-
sicians),whodiedduringthedevelopmentofthisdocumentbutcontributedimmenselytoourunderstandingofnon–ST-elevationacutecoronary
syndromes.
ThisdocumentwasapprovedbytheAmericanCollegeofCardiologyBoardofTrusteesandtheAmericanHeartAssociationScienceAdvisoryand
CoordinatingCommitteeinAugust2014.
TheAmericanCollegeofCardiologyrequeststhatthisdocumentbecitedasfollows:AmsterdamEA,WengerNK,BrindisRG,CaseyDEJr,GaniatsTG,
HolmesDRJr,JaffeAS,JneidH,KellyRF,KontosMC,LevineGN,LiebsonPR,MukherjeeD,PetersonED,SabatineMS,SmallingRW,ZiemanSJ.2014
AHA/ACCguidelineforthemanagementofpatientswithnon–ST-elevationacutecoronarysyndromes:areportoftheAmericanCollegeofCardiology/
AmericanHeartAssociationTaskForceonPracticeGuidelines.JAmCollCardiol2014;64:e139–228.
ThisarticleiscopublishedinCirculation.
Copies:ThisdocumentisavailableontheWorldWideWebsitesoftheAmericanCollegeofCardiology(www.cardiosource.org)andtheAmerican
HeartAssociation(my.americanheart.org).Forcopiesofthisdocument,pleasecontacttheElsevierInc.ReprintDepartment,fax[phone],e-mail
[email protected].
Permissions:Multiplecopies,modification,alteration,enhancement,and/ordistributionofthisdocumentarenotpermittedwithouttheexpress
permission of the American College of Cardiology. Requests may be completed online via the Elsevier site (http://www.elsevier.com/authors/
obtainingpermission-to-re-useelsevier-material).
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e140 Amsterdametal. JACC VOL. 64, NO. 24, 2014
2014AHA/ACCNSTE-ACSGuideline DECEMBER 23, 2014:e139–228
ACC/AHATask JeffreyL.Anderson,MD,FACC,FAHA,Chair RichardJ.Kovacs,MD,FACC,FAHA
ForceMembers JonathanL.Halperin,MD,FACC,FAHA,Chair-Elect E.MagnusOhman,MD,FACC
SusanJ.Pressler,PHD,RN,FAHA
NancyM.Albert,PHD,RN,FAHA FrankW.Sellke,MD,FACC,FAHA
BiykemBozkurt,MD,PHD,FACC,FAHA Win-KuangShen,MD,FACC,FAHA
RalphG.Brindis,MD,MPH,MACC WilliamG.Stevenson,MD,FACC,FAHAyy
LesleyH.Curtis,PHD,FAHA DumindaN.Wijeysundera,MD,PHD
DavidDeMets,PHDyy ClydeW.Yancy,MD,FACC,FAHAyy
LeeA.Fleisher,MD,FACC,FAHA
SamuelGidding,MD,FAHA
RobertA.Guyton,MD,FACCyy yyFormerTaskForcemember;currentmemberduringthe
JudithS.Hochman,MD,FACC,FAHAyy writingeffort.
TABLE OF CONTENTS
PREAMBLE.................................... e142 3.3.2.2. DemographicsandHistoryin
DiagnosisandRiskStratification ....e151
1.INTRODUCTION ............................. e144 3.3.2.3. EarlyEstimationofRisk ..........e151
3.3.2.4. Electrocardiogram.............. e153
1.1. MethodologyandEvidenceReview ..........e144
3.3.2.5. PhysicalExamination............ e153
1.2. OrganizationoftheGWC ...................e144
3.4. CardiacBiomarkersandtheUniversalDefinition
1.3. DocumentReviewandApproval.............e144 ofMI:Recommendations................... e153
1.4. ScopeoftheCPG .........................e144 3.4.1.Biomarkers:Diagnosis ................ e153
3.4.2.Biomarkers:Prognosis................ e154
2.OVERVIEWOFACS .......................... e146
3.4.3.CardiacTroponins ................... e154
2.1. DefinitionofTerms........................e146 3.4.3.1. Prognosis..................... e155
2.2. EpidemiologyandPathogenesis .............e146 3.4.4.CK-MBandMyoglobinComparedWith
Troponin........................... e155
2.2.1.Epidemiology ....................... e146
2.2.2.Pathogenesis........................ e146 3.5. ImmediateManagement ................... e156
3.5.1.DischargeFromtheEDorChestPainUnit:
3.INITIALEVALUATIONANDMANAGEMENT ..... e146 Recommendations ................... e156
3.1. ClinicalAssessmentandInitialEvaluation:
Recommendation .........................e146 4.EARLYHOSPITALCARE ...................... e156
3.1.1.EDorOutpatientFacilityPresentation:
4.1. StandardMedicalTherapies ................ e157
Recommendations ................... e148
4.1.1.Oxygen:Recommendation ............ e157
3.2. DiagnosisofNSTE-ACS ....................e148
4.1.2.Anti-IschemicandAnalgesicMedications .. e158
3.2.1.History ............................ e148 4.1.2.1. Nitrates:Recommendations ...... e158
3.2.2.PhysicalExamination................. e148 4.1.2.2. AnalgesicTherapy:
3.2.3.Electrocardiogram ................... e149 Recommendations.............. e158
3.2.4.BiomarkersofMyocardialNecrosis...... e149 4.1.2.3. Beta-AdrenergicBlockers:
Recommendations.............. e159
3.2.5.Imaging............................ e149
4.1.2.4. CalciumChannelBlockers:
3.3. Prognosis—EarlyRiskStratification: Recommendations.............. e159
Recommendations ........................e149 4.1.2.5. OtherAnti-IschemicInterventions . e160
3.3.1.RationaleforRiskStratificationand 4.1.2.6. CholesterolManagement ........ e160
SpectrumofRisk:High,Intermediate,
andLow ........................... e150 4.2. InhibitorsoftheRenin-Angiotensin-Aldosterone
System:Recommendations ................. e161
3.3.2.EstimationofLevelofRisk ............ e150
3.3.2.1. History:AnginaSymptomsand 4.3. InitialAntiplatelet/AnticoagulantTherapyin
AnginaEquivalents ............. e150 PatientsWithDefiniteorLikelyNSTE-ACS .... e161
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4.3.1.InitialOralandIntravenousAntiplatelet 6.2. MedicalRegimenandUseofMedicationsat
TherapyinPatientsWithDefiniteorLikely Discharge:Recommendations ............... e175
NSTE-ACSTreatedWithanInitialInvasive
6.2.1.LateHospitalandPosthospitalOral
orIschemia-GuidedStrategy: AntiplateletTherapy:Recommendations .. e175
Recommendations ................... e161
4.3.1.1. Aspirin....................... e163 6.2.2.CombinedOralAnticoagulantTherapyand
AntiplateletTherapyinPatientsWith
4.3.1.2. P2Y12ReceptorInhibitors ........ e163 NSTE-ACS .......................... e177
4.3.2.InitialParenteralAnticoagulantTherapyin
PatientsWithDefiniteNSTE-ACS: 6.2.3.PlateletFunctionandGeneticPhenotype
Recommendations ...................e164 Testing ............................ e178
4.3.2.1. Low-Molecular-WeightHeparin ... e165 6.3. RiskReductionStrategiesforSecondary
4.3.2.2. Bivalirudin.................... e165 Prevention............................... e179
4.3.2.3. Fondaparinux ................. e165
6.3.1.CardiacRehabilitationandPhysical
4.3.2.4. UnfractionatedHeparin.......... e165 Activity:Recommendation ............ e179
4.3.2.5. Argatroban ...................e166
6.3.2.PatientEducation:Recommendations ... e179
4.3.3.FibrinolyticTherapyinPatientsWith
DefiniteNSTE-ACS:Recommendation ... e166 6.3.3.PneumococcalPneumonia:
Recommendation.................... e179
4.4. Ischemia-GuidedStrategyVersusEarlyInvasive
6.3.4.NSAIDs:Recommendations............ e179
Strategies ............................... e166
6.3.5.HormoneTherapy:Recommendation ...e180
4.4.1.GeneralPrinciples ................... e166
6.3.6.AntioxidantVitaminsandFolicAcid:
4.4.2.RationaleandTimingforEarlyInvasive
Recommendations................... e181
Strategy ........................... e166
4.4.2.1. RoutineInvasiveStrategyTiming . e166
6.4. PlanofCareforPatientsWithNSTE-ACS:
4.4.3.RationaleforIschemia-GuidedStrategy . e166 Recommendations ........................ e181
4.4.4.EarlyInvasiveandIschemia-Guided 6.4.1.SystemstoPromoteCareCoordination .. e181
Strategies:Recommendations .........e168
4.4.4.1. ComparisonofEarlyVersusDelayed
7.SPECIALPATIENTGROUPS ................... e182
Angiography ................. e169
4.4.5.Subgroups:EarlyInvasiveStrategyVersus 7.1. NSTE-ACSinOlderPatients:Recommendations . e182
Ischemia-GuidedStrategy............. e169
7.2. HF:Recommendations .................... e183
4.4.6.CareObjectives ..................... e169
7.2.1.Arrhythmias ....................... e183
4.5. RiskStratificationBeforeDischargeforPatients
7.2.2.CardiogenicShock:Recommendation... e186
WithanIschemia-GuidedStrategyofNSTE-ACS:
Recommendations ........................ e170 7.3. DiabetesMellitus:Recommendation.........e186
4.5.1.NoninvasiveTestSelection ............ e170 7.3.1.AdjunctiveTherapy ................. e187
4.5.2.SelectionforCoronaryAngiography..... e170
7.4. Post–CABG:Recommendation .............. e187
5.MYOCARDIALREVASCULARIZATION .......... e171
7.5. PerioperativeNSTE-ACSRelatedtoNoncardiac
5.1. PercutaneousCoronaryIntervention.......... e171 Surgery:Recommendations ................e188
5.1.1.PCI—GeneralConsiderations: 7.6. CKD:Recommendations...................e188
Recommendation .....................e171
7.6.1.AntiplateletTherapy ................ e189
5.1.2.PCI—AntiplateletandAnticoagulant
Therapy .............................e171 7.7. Women:Recommendations ................e189
5.1.2.1. OralandIntravenousAntiplatelet
7.8. Anemia,Bleeding,andTransfusion:
Agents:Recommendations ........ e171
Recommendations .......................e190
5.1.2.2. GPIIb/IIIaInhibitors:
Recommendations ...............e172 7.9. Thrombocytopenia ....................... e191
5.1.2.3. AnticoagulantTherapyinPatients
UndergoingPCI:Recommendations ..e173 7.10. CocaineandMethamphetamineUsers:
Recommendations ....................... e191
5.2. TimingofUrgentCABGinPatientsWithNSTE-ACS
inRelationtoUseofAntiplateletAgents: 7.11. Vasospastic(Prinzmetal)Angina:
Recommendations ........................ e174 Recommendations ....................... e192
6.LATEHOSPITALCARE,HOSPITALDISCHARGE, 7.12. ACSWithAngiographicallyNormalCoronary
ANDPOSTHOSPITALDISCHARGECARE........ e175 Arteries:Recommendation................. e193
6.1. GeneralPrinciples(CardioprotectiveTherapyand 7.13. Stress(Takotsubo)Cardiomyopathy:
SymptomManagement).................... e175 Recommendations ....................... e193
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7.14. Obesity.................................e194 comparative-effectiveness data become available (5).
The relationships between CPGs and data standards,
7.15. PatientsTakingAntineoplastic/
ImmunosuppressiveTherapy...............e194 appropriate use criteria, and performance measures are
addressedelsewhere(4).
IntendedUse—CPGsproviderecommendationsapplicable
8.QUALITYOFCAREANDOUTCOMESFORACS—USE
to patients with or at risk of developing cardiovascular
OFPERFORMANCEMEASURESANDREGISTRIES.. e194
disease. The focus is on medical practice in the United
8.1. UseofPerformanceMeasuresandRegistries: States, but CPGs developed in collaboration with other
Recommendation .........................e194
organizations may have a broader target. Although CPGs
maybeusedtoinformregulatoryorpayerdecisions,the
9.SUMMARYANDEVIDENCEGAPS .............. e194
intent is to improve the quality of care and be aligned
withthepatient’sbestinterest.
REFERENCES ................................. e195 Evidence Review—Guideline writing committee (GWC)
members are charged with reviewing the literature;
APPENDIX1
weighing the strength and quality of evidence for or
AuthorRelationshipsWithIndustry against particular tests, treatments, or procedures; and
andOtherEntities(Relevant) ................... e216 estimatingexpectedhealthoutcomeswhendataexist.In
analyzing the data and developing CPGs, the GWC uses
APPENDIX2
evidence-based methodologies developed by the Task
ReviewerRelationshipsWithIndustry Force (6). A key component of the ACC/AHA CPG meth-
andOtherEntities(Relevant) ................... e219 odology is the development of recommendations on the
basis of all available evidence. Literature searches focus
APPENDIX3 on randomized controlled trials (RCTs) but also include
registries, nonrandomized comparative and descriptive
Abbreviations ................................e224
studies, case series, cohort studies, systematic reviews,
andexpertopinion.Onlyselectedreferencesarecitedin
APPENDIX4
the CPG. To ensure that CPGs remain current, new data
AdditionalTables ............................. e225 arereviewedbiannuallybytheGWCsandtheTaskForce
to determine if recommendations should be updated or
PREAMBLE modified. In general, a target cycle of 5 years is planned
forfullrevisions(1).
The American College of Cardiology (ACC) and the Guideline-Directed Medical Therapy—Recognizing ad-
American Heart Association (AHA) are committed to the vances in medical therapy across the spectrum of car-
prevention and management of cardiovascular diseases diovasculardiseases,theTaskForcedesignatedtheterm
through professional education and research for clini- “guideline-directed medical therapy” (GDMT) to repre-
cians, providers, and patients. Since 1980, the ACC and sentrecommendedmedicaltherapyasdefinedmainlyby
AHA have shared a responsibility to translate scientific Class I measures, generally a combination of lifestyle
evidence into clinical practice guidelines (CPGs) with modificationanddrug-anddevice-basedtherapeutics.As
recommendations to standardize and improve car- medical science advances, GDMT evolves, and hence
diovascular health. These CPGs, based on systematic GDMT is preferred to “optimal medical therapy.” For
methods to evaluate and classify evidence, provide a GDMT and all other recommended drug treatment regi-
cornerstoneofqualitycardiovascularcare. mens,thereadershouldconfirmthedosagewithproduct
In response to published reports from the Institute of insert material and carefully evaluate for contraindica-
Medicine (1,2) and the ACC/AHA’s mandate to evaluate tions and possible drug interactions. Recommendations
new knowledge and maintain relevance at the point of arelimitedtotreatments,drugs,anddevicesapprovedfor
care, the ACC/AHA Task Force on Practice Guidelines clinicaluseintheUnitedStates.
(Task Force) began modifying its methodology. This Class of Recommendation and Level of Evidence—Once
modernization effort is published in the 2012 Methodol- recommendationsarewritten,theClassofRecommendation
ogy Summit Report (3) and 2014 perspective article (4). (COR;i.e.,thestrengththeGWCassignstotherecommenda-
The latter recounts the history of the collaboration, tion, which encompasses the anticipated magnitude and
changes over time, current policies, and planned initia- judgedcertaintyofbenefitinproportiontorisk)isassignedby
tives to meet the needs of an evolving healthcare envi- theGWC.Concurrently,theLevelofEvidence(LOE)ratesthe
ronment. Recommendations on value in proportion to scientificevidencesupportingtheeffectoftheinterventionon
resource utilization will be incorporated as high-quality thebasisonthetype,quality,quantity,andconsistencyofdata
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TABLE 1 ApplyingClassificationofRecommendationsandLevelofEvidence
ArecommendationwithLevelofEvidenceBorCdoesnotimplythattherecommendationisweak.Manyimportantclinicalquestionsaddressedintheclinicalpracticeguidelinesdonot
lendthemselvestoclinicaltrials.Althoughrandomizedtrialsareunavailable,theremaybeaveryclearclinicalconsensusthataparticulartestortherapyisusefuloreffective.
*Dataavailablefromclinicaltrialsorregistriesabouttheusefulness/efficacyindifferentsubpopulations,suchassex,age,historyofdiabetesmellitus,historyofpriormyocardial
infarction,historyofheartfailure,andprioraspirinuse.
†Forcomparative-effectivenessrecommendations(ClassIandIIa;LevelofEvidenceAandBonly),studiesthatsupporttheuseofcomparatorverbsshouldinvolvedirectcomparisons
ofthetreatmentsorstrategiesbeingevaluated.
from clinical trials and other reports (Table 1) (4). Unless otherentities(RWI).AllGWCmembersandreviewersare
otherwisestated,recommendationsarepresentedinorderby required to fully disclose current industry relationships
the COR and then the LOE. Where comparative data exist, or personal interests from 12 months before initiation
preferredstrategiestakeprecedence.Whenmorethan1drug, of the writing effort. Management of RWI involves
strategy,ortherapyexistswithinthesameCORandLOEand selectingabalancedGWCandrequiresthatboththechair
therearenocomparativedata,optionsarelistedalphabetically. and a majority of GWC members have no relevant RWI
RelationshipsWithIndustryandOtherEntities—TheACC (see Appendix 1 for the definition of relevance). GWC
and AHA exclusively sponsor the work of GWCs without members are restricted with regard to writing or voting
commercial support, and members volunteer their time on sections to which their RWI apply. In addition, for
for this activity. The Task Force makes every effort to transparency, GWC members’ comprehensive disclosure
avoid actual, potential, or perceived conflicts of interest information is available as an online supplement. Com-
that might arise through relationships with industry or prehensive disclosure information for the Task Force is
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2014AHA/ACCNSTE-ACSGuideline DECEMBER 23, 2014:e139–228
available as an additional supplement. The Task Force receptorinhibitor,percutaneouscoronaryintervention,renin-
strives to avoid bias by selecting experts from a broad angiotensin-aldosterone inhibitors, secondary prevention,
array of backgrounds representing different geographic smoking cessation, statins, stent, thienopyridines, troponins,
regions, sexes, ethnicities, races, intellectual perspec- unstable angina, and weight management. Additionally, the
tives/biases, and scopes of clinical practice. Selected or- GWCrevieweddocumentsrelatedtonon–ST-elevationacute
ganizations and professional societies with related coronarysyndrome(NSTE-ACS)previouslypublishedbythe
interests andexpertise are invited to participate as part- ACC and AHA. References selected and published in this
nersorcollaborators. documentarerepresentativeandnotall-inclusive.
IndividualizingCareinPatientsWithAssociatedConditions
and Comorbidities—The ACC and AHA recognize the 1.2. OrganizationoftheGWC
complexity of managing patients with multiple condi- TheGWCwascomposedofclinicians,cardiologists,internists,
tions, compared with managing patients with a single interventionists, surgeons, emergency medicine specialists,
disease, and the challenge is compounded when CPGs family practitioners, and geriatricians. The GWC included
forevaluationortreatmentofseveralcoexistingillnesses representativesfromtheACCandAHA,AmericanAcademyof
are discordant or interacting (7). CPGs attempt to define Family Physicians, American College of Emergency Physi-
practicesthatmeettheneedsofpatientsinmost,butnot cians,AmericanCollegeofPhysicians,SocietyforCardiovas-
all,circumstancesanddonotreplaceclinicaljudgment. cular Angiography and Interventions (SCAI), and Society of
Clinical Implementation—Management in accordance ThoracicSurgeons(STS).
with CPG recommendations is effective only when fol-
1.3. DocumentReviewandApproval
lowed; therefore, to enhance their commitment to treat-
mentandcompliancewithlifestyleadjustment,clinicians Thisdocumentwasreviewedby2officialreviewerseach
should engage the patient to participate in selecting nominatedbytheACCandAHA;1reviewereachfromthe
interventions on the basis of the patient’s individual American Academy of Family Physicians, American Col-
valuesandpreferences,takingassociatedconditionsand lege of Emergency Physicians, SCAI, and STS; and 37
comorbidities into consideration (e.g., shared decision individual content reviewers (including members of the
making).Consequently,therearecircumstancesinwhich American Association of Clinical Chemistry, ACC Heart
deviationsfromtheseguidelinesareappropriate. Failure and Transplant Section Leadership Council, ACC
TherecommendationsinthisCPGaretheofficialpolicyof Cardiovascular Imaging Section Leadership Council, ACC
theACCandAHAuntiltheyaresupersededbyapublished Interventional Section Leadership Council, ACC Preven-
addendum,focusedupdate,orrevisedfull-textCPG. tionofCardiovascularDiseaseCommittee,ACCSurgeons’
JeffreyL.Anderson,MD,FACC,FAHA Council, Association of International Governors, and
Chair,ACC/AHATaskForceonPracticeGuidelines Department of Health and Human Services). Reviewers’
RWIinformationwasdistributedtotheGWCandispub-
1. INTRODUCTION lishedinthisdocument(Appendix2).
This document was approved for publication by the
1.1. MethodologyandEvidenceReview governing bodies of the ACC and the AHA and endorsed
The recommendations listed in this CPG are, whenever bytheAmericanAssociationforClinicalChemistry,SCAI,
possible,evidencebased.Anextensiveevidencereviewwas andtheSTS.
conducted through October 2012, and other selected refer-
1.4. ScopeoftheCPG
ences published through April 2014 were reviewed by the
GWC. Literature included was derived from research The2014NSTE-ACSCPGisafullrevisionofthe2007ACCF/
involvinghumansubjects,publishedinEnglish,andindexed AHACPGforthemanagementofpatientswithunstableangina
in MEDLINE (through PubMed), EMBASE, the Cochrane (UA) and non–ST-elevation myocardial infarction (NSTEMI)
Library,AgencyforHealthcareResearchandQualityReports, and the 2012 focused update (8). The new title, “Non–ST-
andotherselecteddatabasesrelevanttothisCPG.Therele- ElevationAcuteCoronarySyndromes,”emphasizesthecon-
vantdataareincludedinevidencetablesintheOnlineData tinuumbetweenUAandNSTEMI.Atpresentation,patients
Supplement. Key search words included but were not withUAandNSTEMIcanbeindistinguishableandarethere-
limitedtothefollowing:acutecoronarysyndrome,anticoag- foreconsideredtogetherinthisCPG.
ulanttherapy,antihypertensives,anti-ischemictherapy,anti- In the United States, NSTE-ACS affects >625,000
platelet therapy, antithrombotic therapy, beta blockers, patientsannually,*oralmostthreefourthsofallpatients
biomarkers, calcium channel blockers, cardiac rehabilitation, withacutecoronarysyndrome(ACS)(9).Inselectingthe
conservativemanagement,diabetesmellitus,glycoproteinIIb/
IIIainhibitors,heartfailure,invasivestrategy,lifestylemodifi-
cation,myocardialinfarction,nitrates,non–ST-elevation,P2Y12 *Estimateincludessecondarydischargediagnoses.
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initial approach to care, the term “ischemia-guided guide the clinician in improving outcomes for patients
strategy” has replaced the previous descriptor, “initial with NSTE-ACS. Table 2 lists documents deemed per-
conservative management,” to more clearly convey the tinent to this effort and is intended for use as a re-
physiologicalrationaleofthisapproach. source, thus obviating the need to repeat extant CPG
The task of the 2014 GWC was to establish a contem- recommendations.
poraryCPGfortheoptimalmanagementofpatientswith The GWC abbreviated the discussion sections to
NSTE-ACS.Itincorporatesbothestablishedandnewevi- include an explanation of salient information related to
dence from published clinical trials, as well as informa- therecommendations.Incontrasttotextbookdeclaratory
tion from basic science and comprehensive review presentations, explanations were supplemented with
articles. These recommendations were developed to evidencetables.TheGWCalsoprovidedabriefsummary
TABLE 2 AssociatedCPGsandStatements
PublicationYear
Title Organization (Reference)
CPGs
Stableischemicheartdisease ACC/AHA/AATS/PCNA/SCAI/STS 2014(10)*
2012(11)
Atrialfibrillation AHA/ACC/HRS 2014(12)
Assessmentofcardiovascularrisk ACC/AHA 2013(13)
Heartfailure ACC/AHA 2013(14)
Lifestylemanagementtoreducecardiovascularrisk AHA/ACC 2013(15)
Managementofoverweightandobesityinadults AHA/ACC/TOS 2013(16)
ST-elevationmyocardialinfarction ACC/AHA 2013(17)
Treatmentofbloodcholesteroltoreduceatheroscleroticcardiovascularriskinadults ACC/AHA 2013(18)
AcutemyocardialinfarctioninpatientspresentingwithST-segmentelevation ESC 2012(19)
Device-basedtherapy ACC/AHA/HRS 2013(20)
Thirduniversaldefinitionofmyocardialinfarction ESC/ACC/AHA/WHF 2012(21)
AcutecoronarysyndromesinpatientspresentingwithoutpersistentST-segmentelevation ESC 2011(22)
Coronaryarterybypassgraftsurgery ACC/AHA 2011(23)
Hypertrophiccardiomyopathy ACC/AHA 2011(24)
Effectiveness-basedguidelinesforthepreventionofcardiovasculardiseaseinwomen AHA/ACC 2011(25)
Percutaneouscoronaryintervention ACC/AHA/SCAI 2011(26)
Secondarypreventionandriskreductiontherapyforpatientswithcoronaryandother AHA/ACC 2011(27)
atheroscleroticvasculardisease
Assessmentofcardiovascularriskinasymptomaticadults ACC/AHA 2010(28)
Myocardialrevascularization ESC 2010(29)
Unstableanginaandnon–ST-elevationmyocardialinfarction NICE 2010(30)†
Guidelinesforcardiopulmonaryresuscitationandemergencycardiovascularcare—part9: AHA 2010(31)
postcardiacarrestcare
Seventhreportofthejointnationalcommitteeonprevention,detection,evaluation,and NHLBI 2003(32)
treatmentofhighbloodpressure
Statements
Keydataelementsanddefinitionsformeasuringtheclinicalmanagementandoutcomesof ACC/AHA 2013(33)
patientswithacutecoronarysyndromesandcoronaryarterydisease
Practicalclinicalconsiderationsintheinterpretationoftroponinelevations ACC 2012(34)
Testingoflow-riskpatientspresentingtotheemergencydepartmentwithchestpain AHA 2010(35)
Primarypreventionofcardiovasculardiseasesinpeoplewithdiabetesmellitus AHA/ADA 2007(36)
Preventionandcontrolofinfluenza CDC 2005(37)
*Thefull-textSIHDCPGisfrom2012(11).Afocusedupdatewaspublishedin2014(10).
†Minormodificationsweremadein2013.Forafullexplanationofthechanges,seehttp://publications.nice.org.uk/unstable-angina-and-nstemi-cg94/changes-after-publication.
AATSindicatesAmericanAssociationforThoracicSurgery;ACC,AmericanCollegeofCardiology;ADA,AmericanDiabetesAssociation;AHA,AmericanHeartAssociation;CDC,Centers
forDiseaseControlandPrevention;CPG,clinicalpracticeguideline;ESC,EuropeanSocietyofCardiology;HRS,HeartRhythmSociety;NHLBI,NationalHeart,Lung,andBloodInstitute;
NICE,NationalInstituteforHealthandClinicalExcellence;PCNA,PreventiveCardiovascularNursesAssociation;SCAI,SocietyforCardiovascularAngiographyandInterventions;SIHD,
stableischemicheartdisease;STS,SocietyofThoracicSurgeons;TOS,TheObesitySociety;andWHF,WorldHeartFederation.
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e146 Amsterdametal. JACC VOL. 64, NO. 24, 2014
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of the relevant recommendations and references related myocardial oxygen supply and/or increased myocardial
tosecondarypreventionratherthandetailedreiteration. oxygendemand(intheabsenceofadirectcoronaryartery
Throughout, the goal was to provide the clinician with process)asaMItype2(Appendix4,TableAandSection
concise,evidence-basedcontemporaryrecommendations 3.4foranadditionaldiscussiononthediagnosisofMI).
and the supporting documentation to encourage their
2.2. EpidemiologyandPathogenesis
application.
2.2.1. Epidemiology
2. OVERVIEW OF ACS
IntheUnitedStates,themedianageatACSpresentation
is68years(interquartilerange56to79),andthemale-to-
2.1. DefinitionofTerms
femaleratioisapproximately3:2(40).Somepatientshave
ACShasevolvedasausefuloperationaltermthatrefersto a history of stable angina, whereas in others, ACS is the
a spectrum of conditions compatible with acute myocar- initialpresentationofcoronaryarterydisease(CAD).Itis
dialischemiaand/orinfarctionthatareusuallyduetoan estimatedthatintheUnitedStates,eachyear,>780,000
abruptreductionincoronarybloodflow(Figure1).Akey persons will experience an ACS. Approximately 70% of
branch point is ST-segment elevation (ST-elevation) or these will have NSTE-ACS (9). Patients with NSTE-ACS
new left bundle-branch block on the electrocardiogram typically have more comorbidities, both cardiac and
(ECG), which is an indication for immediate coronary noncardiac,thanpatientswithSTEMI.
angiography to determine if there is an indication for
reperfusiontherapytoopenalikelycompletelyoccluded 2.2.2. Pathogenesis
coronary artery. Separate CPGs have been developed for The hallmark of ACS is the sudden imbalance between
ST-elevationmyocardialinfarction(STEMI)(17). myocardial oxygen consumption (MVO ) and demand,
2
The absence of persistent ST-elevation is suggestive whichisusuallytheresultofcoronaryarteryobstruction.
of NSTE-ACS (except in patients with true posterior The imbalance may also be caused by other conditions,
myocardial infarction [MI], Sections 3.3.2.4, 4.3.2, and including excessive myocardial oxygen demand in the
7.2.2).NSTE-ACScanbefurthersubdividedonthebasisof setting of a stable flow-limiting lesion; acute coronary
cardiac biomarkers of necrosis (e.g., cardiac troponin, insufficiency due to other causes (e.g., vasospastic
Sections3.2.4and3.4).Ifcardiacbiomarkersareelevated [Prinzmetal] angina [Section 7.11], coronary embolism,
and the clinical context is appropriate, the patient is coronary arteritis); noncoronary causes of myocardial
considered to have NSTEMI (34); otherwise, the patient oxygen supply-demand mismatch (e.g., hypotension,
is deemed to have UA. ST depression, transient ST- severe anemia, hypertension, tachycardia, hypertrophic
elevation, and/or prominent T-wave inversions may be cardiomyopathy, severe aortic stenosis); nonischemic
present but are not required for a diagnosis of NSTEMI. myocardial injury (e.g., myocarditis, cardiac contusion,
Abnormalities on the ECG and elevated troponins in cardiotoxicdrugs);andmultifactorialcausesthatarenot
isolationareinsufficienttomakethediagnosisofACSbut mutually exclusive (e.g., stress[Takotsubo] cardiomyop-
must be interpreted in the appropriate clinical context. athy [Section 7.13], pulmonary embolism, severe heart
Thus, UA and NSTEMI are closely related conditions failure[HF],sepsis)(41).
whosepathogenesisandclinicalpresentationsaresimilar
3. INITIAL EVALUATION AND MANAGEMENT
but vary in severity. The conditions differ primarily by
whethertheischemiaissevereenoughtocausemyocar-
dial damage leading to detectable quantities of myocar- 3.1. ClinicalAssessmentandInitialEvaluation:
dial injury biomarkers. The term “possible ACS” is often Recommendation
assignedduringinitialevaluationiftheECGisunreveal- CLASSI
ing and troponin data are not yet available. UA can pre- 1. Patients with suspected ACS should be risk stratified based
sent without any objective data of myocardial ischemic onthelikelihoodofACSandadverseoutcome(s)todecideon
injury (normal ECG and normal troponin), in which case the need for hospitalization and assist in the selection of
theinitialdiagnosisdependssolelyonthepatient’sclin- treatmentoptions(42–44).(LevelofEvidence:B)
ical history and the clinician’s interpretation and judg-
Patients with suspected ACS must be evaluated rapidly to
ment. However, with the increasing sensitivity of
identify those with a life-threatening emergency versus
troponin assays, biomarker-negative ACS (i.e., UA) is
those with a more benign condition. The goalof the initial
becoming rarer (39). The pathogenesis of ACS is consid-
evaluationfocusesonanswering2questions:
ered in the “Third Universal Definition of Myocardial
Infarction” (21). This statement defines MI caused by a 1. What is the likelihood that the symptoms and signs
primary coronary artery process such as spontaneous representACS?
plaque rupture as MI type 1 and one related to reduced 2. Whatisthelikelihoodofadverseclinicaloutcome(s)?
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DECEMBER 23, 2014:e139–228 2014AHA/ACCNSTE-ACSGuideline
FIGURE1 AcuteCoronarySyndromes
ThetophalfofthefigureillustratestheprogressionofplaqueformationandonsetandcomplicationsofNSTE-ACS,withmanagementateachstage.The
numberedsectionofanarterydepictstheprocessofatherogenesisfrom1)normalarteryto2)extracellularlipidinthesubintimato3)fibrofattystageto4)
procoagulantexpressionandweakeningofthefibrouscap.ACSdevelopswith5)disruptionofthefibrouscap,whichisthestimulusforthrombogenesis.6)
Thrombusresorptionmaybefollowedbycollagenaccumulationandsmoothmusclecellgrowth.Thrombusformationandpossiblecoronaryvasospasm
reducebloodflowintheaffectedcoronaryarteryandcauseischemicchestpain.Thebottomhalfofthefigureillustratestheclinical,pathological,elec-
trocardiographic,andbiomarkercorrelatesinACSandthegeneralapproachtomanagement.Flowreductionmayberelatedtoacompletelyocclusive
thrombus(bottomhalf,rightside)orsubtotallyocclusivethrombus(bottomhalf,leftside).MostpatientswithST-elevation(thickwhitearrowinbottom
panel)developQwMI,andafew(thinwhitearrow)developNQMI.ThosewithoutST-elevationhaveeitherUAorNSTEMI(thickredarrows),adistinction
basedoncardiacbiomarkers.MostpatientspresentingwithNSTEMIdevelopNQMI;afewmaydevelopQwMI.Thespectrumofclinicalpresentations
includingUA,NSTEMI,andSTEMIisreferredtoasACS.ThisNSTE-ACSCPGincludessectionsoninitialmanagementbeforeNSTE-ACS,attheonsetofNSTE-
ACS,andduringthehospitalphase.Secondarypreventionandplansforlong-termmanagementbeginearlyduringthehospitalphase.Patientswith
noncardiacetiologiesmakeupthelargestgrouppresentingtotheEDwithchestpain(dashedarrow).
*Elevatedcardiacbiomarker(e.g.,troponin),Section3.4.
ACSindicatesacutecoronarysyndrome;CPG,clinicalpracticeguideline;Dx,diagnosis;ECG,electrocardiogram;ED,emergencydepartment;MI,myocardial
infarction;NQMI,non–Q-wavemyocardialinfarction;NSTE-ACS,non–ST-elevationacutecoronarysyndromes;NSTEMI,non–ST-elevationmyocardial
infarction;QwMI,Q-wavemyocardialinfarction;STEMI,ST-elevationmyocardialinfarction;andUA,unstableangina.
ModifiedwithpermissionfromLibbyetal.(38).
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e148 Amsterdametal. JACC VOL. 64, NO. 24, 2014
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Risk assessment scores and clinical prediction algorithms 3.2. DiagnosisofNSTE-ACS
using clinical history, physical examination, ECG, and DifferentialdiagnosisofNSTE-ACSincludes(41):
cardiac troponins have been developed to help identify
(cid:2) Nonischemic cardiovascular causes of chest pain
patientswithACSatincreasedriskofadverseoutcome(s).
(e.g., aortic dissection, expanding aortic aneurysm,
Common risk assessment tools include the TIMI (Throm-
pericarditis,pulmonaryembolism)
bolysis In Myocardial Infarction) risk score (42), the PUR-
(cid:2) Noncardiovascular causes of chest, back, or upper
SUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina:
abdominaldiscomfortinclude:
Receptor Suppression Using Integrilin Therapy) risk score
o Pulmonary causes (e.g., pneumonia, pleuritis,
(43), the GRACE (Global Registry of Acute Coronary
pneumothorax)
Events) risk score (44), and the NCDR-ACTION (National
o Gastrointestinal causes (e.g., gastroesophageal re-
Cardiovascular Data Registry-Acute Coronary Treatment
flux, esophageal spasm, peptic ulcer, pancreatitis,
and Intervention Outcomes Network) registry (https://
biliarydisease)
www.ncdr.com/webncdr/action/). These assessment tools
have been applied with variable efficacy to predict out- o Musculoskeletal causes (e.g., costochondritis, cervi-
calradiculopathy)
comes in patients presenting to the emergency depart-
ment (ED) with undifferentiated chest pain (“pain” o Psychiatricdisorders
o Otheretiologies(e.g.,sicklecellcrisis,herpeszoster)
encompasses not only pain, but also symptoms such as
discomfort,pressure,andsqueezing)(45–48).TheSanchis Inaddition,theclinicianshoulddifferentiateNSTE-ACSfrom
score (49), Vancouver rule (50), Heart (History, ECG, Age, acute coronary insufficiency due to a nonatherosclerotic
RiskFactors,andTroponin)score(51),HEARTS3score(52), causeandnoncoronarycausesofmyocardialoxygensupply-
and Hess prediction rule (53) were developed specifically demandmismatch(41)(Section2.2.2).
for patients in the ED with chest pain. Although no
definitive study has demonstrated the superiority of risk
3.2.1. History
assessmentscoresorclinicalpredictionrulesoverclinician
NSTE-ACS most commonly presents as a pressure-type
judgment, determination of the level of risk on initial
chest pain that typically occurs at rest or with minimal
evaluation is imperative to guide patient management,
exertion lasting $10 minutes (41). The pain most
including the need for additional diagnostic testing and
frequently starts in the retrosternal area and can radiate
treatment. See Section 3.2.2 for a discussion of risk strat-
ification variables. toeitherorbotharms,theneck,orthejaw.Painmayalso
occur in these areas independent of chest pain. Patients
SeeOnlineDataSupplement1foradditionalinformation
with NSTE-ACS may also present with diaphoresis, dys-
onclinicalassessmentandinitialevaluation.
pnea, nausea, abdominal pain, or syncope. Unexplained
new-onset or increased exertional dyspnea is the most
3.1.1. EDorOutpatientFacilityPresentation:Recommendations
common angina equivalent. Less common presentations
CLASSI include nausea and vomiting, diaphoresis, unexplained
1. Patients with suspected ACS and high-risk features such as fatigue,andsyncope.Factorsthatincreasetheprobability
continuingchestpain,severedyspnea,syncope/presyncope, ofNSTE-ACSareolderage,malesex,positivefamilyhis-
orpalpitationsshouldbereferredimmediatelytotheEDand tory of CAD, and the presence of peripheral arterial
transported by emergencymedical services when available. disease, diabetes mellitus, renal insufficiency, prior MI,
(LevelofEvidence:C)
and prior coronary revascularization. Although older pa-
tients($75yearsofage)andwomenusuallypresentwith
CLASSIIb typical symptoms of ACS, the frequency of atypical pre-
1. Patients with less severe symptoms may be considered for sentationsisincreasedinthesegroupsaswellasinpatients
referraltotheED,achestpainunit,orafacilitycapableof with diabetes mellitus, impaired renal function, and
performing adequate evaluation depending on clinical dementia(54,55).Atypicalsymptoms,includingepigastric
circumstances.(LevelofEvidence:C) pain,indigestion,stabbingorpleuriticpain,andincreasing
dyspneaintheabsenceofchestpainshouldraiseconcern
PatientswithsuspectedACSandhigh-riskfeaturesshouldbe
forNSTE-ACS(56).Psychiatricdisorders(e.g.,somatoform
transportedtotheEDbyemergencymedicalserviceswhen
disorders,panicattack,anxietydisorders)arenoncardiac
available.Hospitalsandoutpatientfacilitiesshouldprovide
causesofchestpainthatcanmimicACS(57).
clearly visible signage directing patients transported by
private vehicle to the appropriate triage area. Outpatient
facilities should have the capacity for ECG and cardiac 3.2.2. PhysicalExamination
troponin measurements with immediate ED referral for ThephysicalexaminationinNSTE-ACScanbenormal,but
thoseconsideredtohaveACS. signsofHFshouldexpeditethediagnosisandtreatment
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