2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST

38 Pages·2007·1.8 MB·English

JournaloftheAmericanCollegeofCardiology Vol.51,No.2,2008
©2008bytheAmericanCollegeofCardiologyFoundationandtheAmericanHeartAssociation,Inc. ISSN0735-1097/08/$34.00
PublishedbyElsevierInc. doi:10.1016/j.jacc.2007.10.001
STEMI FOCUSED UPDATE
2007 Focused Update of the ACC/AHA
2004 Guidelines for the Management of
Patients With ST-Elevation Myocardial Infarction
A Report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines
Developed in Collaboration With the Canadian Cardiovascular Society
Endorsed by the American Academy of Family Physicians
2007WritingGrouptoReviewNewEvidenceandUpdatethe
ACC/AHA2004GuidelinesfortheManagementofPatientsWithST-ElevationMyocardialInfarction,
WritingonBehalfofthe2004WritingCommittee
Elliott M. Antman, MD, FACC, FAHA, Charles J. Mullany, MB, MS, FACC
Co-Chair*† David L. Pearle, MD, FACC, FAHA
Mary Hand, MSPH, RN, FAHA, Co-Chair Michael A. Sloan, MD, FACC
Sidney C. Smith, JR, MD, FACC, FAHA§§
Paul W. Armstrong, MD, FACC, FAHA‡§
Eric R. Bates, MD, FACC, FAHA *Chairof2004WritingCommittee;
Lee A. Green, MD, MPH(cid:1) †RecusedfromvotingonSection8:AnticoagulantsasAncillaryTherapyand
Section10:Anticoagulants;
Lakshmi K. Halasyamani, MD¶ ‡RecusedfromvotingonSection5:FacilitatedPCI;
§CanadianCardiovascularSocietyRepresentative;
Judith S. Hochman, MD, FACC, FAHA** (cid:1)AmericanAcademyofFamilyPhysiciansRepresentative;
Harlan M. Krumholz, MD, FACC, FAHA†† ¶AmericanCollegeofPhysiciansRepresentative;
**RecusedfromvotingonSection7:PCIAfterFibrinolysisorforPatients
Gervasio A. Lamas, MD, FACC**
NotUndergoingPrimaryReperfusion;
††PerformanceMeasuresLiaison;
§§RecusedfromvotingonSection13:AntiplateletTherapy
2004 Elliott M. Antman, MD, FACC, FAHA, Chair Harlan M. Krumholz, MD, FACC, FAHA
Writing
Frederick G. Kushner, MD, FACC, FAHA
Committee
Daniel T. Anbe, MD, FACC, FAHA Gervasio A. Lamas, MD, FACC
Members
Paul W. Armstrong, MD, FACC, FAHA Charles J. Mullany, MB, MS, FACC
Eric R. Bates, MD, FACC, FAHA Joseph P. Ornato, MD, FACC, FAHA
Lee A. Green, MD, MPH David L. Pearle, MD, FACC, FAHA
Mary Hand, MSPH, RN, FAHA Michael A. Sloan, MD, FACC
Judith S. Hochman, MD, FACC, FAHA Sidney C. Smith, JR, MD, FACC, FAHA
JACCVol.51,No.2,2008 Antmanetal. 211
January15,2008:210–47 STEMIFocusedUpdate
Task SidneyC.Smith,JR,MD,FACC,FAHA,Chair HarlanM.Krumholz,MD,FACC,FAHA
Force
AliceK.Jacobs,MD,FACC,FAHA,Vice-Chair FrederickG.Kushner,MD,FACC,FAHA
Members
BruceW.Lytle,MD,FACC,FAHA
CynthiaD.Adams,MSN,PHD,FAHA‡‡ RickNishimura,MD,FACC,FAHA
JeffreyL.Anderson,MD,FACC,FAHA‡‡ RichardL.Page,MD,FACC,FAHA
ChristopherE.Buller,MD,FACC BarbaraRiegel,DNSC,RN,FAHA‡‡
MarkA.Creager,MD,FACC,FAHA LynnG.Tarkington,RN
StevenM.Ettinger,MD,FACC ClydeW.Yancy,MD,FACC
JonathanL.Halperin,MD,FACC,FAHA‡‡
SharonA.Hunt,MD,FACC,FAHA‡‡ ‡‡FormerTaskForcememberduringthiswritingeffort
6. ImmediateorEmergencyInvasiveStrategy
TABLE OF CONTENTS
andRescuePCI.........................................220
Preamble .....................................................211 7. PCIAfterFibrinolysisorforPatientsNot
UndergoingPrimaryReperfusion ....................223
1. Introduction .............................................213
7.1. TheLateOpenArteryHypothesis:
1.1. EvidenceReview ...................................213 ClinicalOutcomes..................................223
1.2. OrganizationofCommitteeand 7.2. TheLateOpenArteryHypothesis:
RelationshipsWithIndustry.......................214 AngiographicOutcomes............................223
1.3. ReviewandApproval...............................214 7.3. Conclusion ..........................................223
2. Analgesia ................................................214 8. AncillaryTherapy .......................................224
3. BetaBlockers...........................................215 8.1. Conclusion ..........................................225
9. Thienopyridines.........................................230
3.1. COMMIT/CCS-2(Metoprolol)......................216
3.2. Conclusion ..........................................216 9.1. Conclusion ..........................................231
4. Reperfusion .............................................217 10.Anticoagulants..........................................231
4.1. LogisticsofCare ...................................217 11.InvasiveEvaluation ....................................232
5. FacilitatedPCI ..........................................219
12.SecondaryPrevention.................................232
Thisdocumentisalimitedupdatetothe2004guidelinesupdateandisbasedona 13.AntiplateletTherapy ...................................237
reviewofcertainevidence,notafullliteraturereview.
ThisdocumentwasapprovedbytheAmericanCollegeofCardiologyBoardof
TrusteesinOctober2007andbytheAmericanHeartAssociationScienceAdvisory References...................................................238
andCoordinatingCommitteeOctober2007.
The American College of Cardiology Foundation and the American Heart Appendix1 ...................................................241
Associationrequestthatthisdocumentbecitedasfollows:AntmanEM,HandM,
ArmstrongPW,BatesER,GreenLA,HalasyamaniLK,HochmanJS,Krumholz
HM,LamasGA,MullanyCJ,PearleDL,SloanMA,SmithSCJr.2007focused Appendix2 ...................................................243
updateoftheACC/AHA2004GuidelinesfortheManagementofPatientsWith
ST-ElevationMyocardialInfarction:areportoftheAmericanCollegeofCardiology/
AmericanHeartAssociationTaskForceonPracticeGuidelines(WritingGroupto
Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Preamble
Management of Patients With ST-Elevation Myocardial Infarction). J Am Coll
Cardiol2008;51:210–47.
ThisarticlehasbeencopublishedintheJanuary15,2008,issueofCirculation.
Aprimarychallengeinthedevelopmentofclinicalpractice
Copies:ThisdocumentisavailableontheWorldWideWebsitesoftheAmerican
College of Cardiology (www.acc.org) and the American Heart Association guidelinesiskeepingpacewiththestreamofnewdataupon
(www.americanheart.org).Forcopiesofthisdocument,pleasecontactElsevierInc, which recommendations are based. In an effort to respond
ReprintDepartment,fax[phone],[email protected].
more quickly to new evidence, the American College of
Permissions: Modification, alteration, enhancement and/or distribution of this
documentarenotpermittedwithouttheexpresspermissionoftheAmericanCollege Cardiology/American Heart Association (ACC/AHA)
of Cardiology and the American Heart Association. Please contact the American Task Force on Practice Guidelines has created a new
Heart Association. Instructions for obtaining permission are located at http://
www.americanheart.org/presenter.jhtml?identifier(cid:1)4431.Alinktothe“Permission “focused update” process to revise the existing guideline
RequestForm”appearsontherightsideofthepage. recommendations that are affected by evolving data or
212 Antmanetal. JACCVol.51,No.2,2008
STEMIFocusedUpdate January15,2008:210–47
opinion. Before the initiation of this focused approach, update. Of note, the implications of older studies that have
periodic updates and revisions of existing guidelines re- informed recommendations but have not been repeated in
quired up to 3 years to complete. Now, however, new contemporarysettingsarecarefullyconsidered.
evidence will be reviewed in an ongoing fashion to more The ACC/AHA practice guidelines address patient popu-
efficiently respond to important science and treatment lations(andhealthcareproviders)residinginNorthAmerica.
trends that could have a major impact on patient outcomes As such, drugs that are not currently available in North
andqualityofcare.Evidencewillbereviewedatleasttwice America are discussed in the text without a specific class of
ayear,andupdateswillbeinitiatedonanasneededbasisas recommendation. For studies performed in large numbers of
quickly as possible, while maintaining the rigorous meth- subjects outside of North America, each writing committee
odology that the ACC and AHA have developed during reviewsthepotentialimpactofdifferentpracticepatternsand
their more than 20 years of partnership. patientpopulationsonthetreatmenteffectandontherelevanceto
Theseupdatedguidelinerecommendationsreflectacon- the ACC/AHA target population to determine whether the
sensus of expert opinion following a thorough review that findingsshouldinformaspecificrecommendation.
consisted primarily of late-breaking clinical trials identified TheACC/AHApracticeguidelinesareintendedtoassist
through a broad-based vetting process as important to the healthcareprovidersinclinicaldecisionmakingbydescrib-
relevantpatientpopulationandofothernewdatadeemedto ing a range of generally acceptable approaches for the
haveanimpactonpatientcare(seeSection1.1fordetailson diagnosis, management, and prevention of specific diseases
this focused update). It is important to note that this or conditions. The guidelines attempt to define practices
focusedupdateisnotintendedtorepresentanupdatebased thatmeettheneedsofmostpatientsinmostcircumstances.
on a full literature review from the date of the previous Theultimatejudgmentregardingcareofaparticularpatient
guideline publication. Specific criteria/considerations for must be made by the health care provider and patient in
inclusion of new data include: light of all the circumstances presented by that patient.
• Publication in a peer-reviewed journal Thus, there are circumstances in which deviations from
• Large, randomized, placebo-controlled trial(s) theseguidelinesmaybeappropriate.Clinicaldecisionmak-
• Nonrandomized data deemed important on the basis of ing should consider the quality and availability of expertise
intheareawherecareisprovided.Theseguidelinesmaybe
resultsthatimpactcurrentsafetyandefficacyassumptions
• Strengths/weaknessofresearchmethodologyandfindings used as the basis for regulatory or payer decisions, but the
• Likelihoodofadditionalstudiesinfluencingcurrentfindings ultimategoalisqualityofcareandservingthepatient’sbest
• Impact on current performance measure(s) and/or likeli- interests.
Prescribed courses of treatment in accordance with these
hoodoftheneedtodevelopnewperformancemeasure(s)
• Requests and requirements for review and update from recommendations are only effective if they are followed by
thepatient.Becauselackofpatientadherencemayadversely
the practice community, key stakeholders, and other
affect treatment outcomes, health care providers should
sources free of relationships with industry or other
make every effort to engage the patient in active participa-
potential bias
• Number of previous trials showing consistent results tion with prescribed treatment.
• Need for consistency with other guidelines or guideline TheACC/AHATaskForceonPracticeGuidelinesmakes
everyefforttoavoidanyactual,potential,orperceivedconflict
revisions
of interest arising from industry relationships or personal
Inanalyzingthedataanddevelopingupdatedrecommen- interestsofawritingcommitteemember.Allwritingcommit-
dations and supporting text, the focused update writing tee members and peer reviewers were required to provide
groupusedevidence-basedmethodologiesdevelopedbythe disclosurestatementsofallsuchrelationshipspertainingtothe
ACC/AHA Task Force on Practice Guidelines, which are trialsandotherevidenceunderconsideration(seeAppendixes
described elsewhere (1,2). 1 and 2). Final recommendations were balloted to all writing
The schema for class of recommendation and level of committee members. Writing committee members with sig-
evidenceissummarizedinTable1,whichalsoillustrateshow nificant (greater than $10 000) relevant relationships with
the grading system provides estimates of the size of the industry (RWI) were required to recuse themselves from
treatmenteffectandthecertaintyofthetreatmenteffect.Note votingonthatrecommendation.Writingcommitteemembers
that a recommendation with Level of Evidence B or C does whodidnotparticipatearenotlistedasauthorsofthisfocused
notimplythattherecommendationisweak.Manyimportant update.
clinical questions addressed in guidelines do not lend them- Withtheexceptionoftherecommendationspresentedhere,
selvestoclinicaltrials.Althoughrandomizedtrialsmaynotbe thefullguidelinesremaincurrent.Onlytherecommendations
available, there may be a very clear clinical consensus that a fromtheaffectedsection(s)ofthefullguidelinesareincludedin
particulartestortherapyisusefulandeffective.Boththeclass this focused update. For easy reference, all recommendations
ofrecommendationandlevelofevidencelistedinthefocused from any section of guidelines impacted by a change are
updatesarebasedonconsiderationoftheevidencereviewedin presented with a notation as to whether they remain current,
previous iterations of the guidelines as well as the focused are new, or have been modified. When evidence impacts
JACCVol.51,No.2,2008 Antmanetal. 213
January15,2008:210–47 STEMIFocusedUpdate
Table1. ApplyingClassificationofRecommendationsandLevelofEvidence†
(cid:1)Dataavailablefromclinicaltrialsorregistriesabouttheusefulness/efficacyindifferentsubpopulations,suchasgender,age,historyofdiabetes,historyofpriormyocardialinfarction,historyofheart
failure,andprioraspirinuse.ArecommendationwithLevelofEvidenceBorCdoesnotimplythattherecommendationisweak.Manyimportantclinicalquestionsaddressedintheguidelinesdonot
lendthemselvestoclinicaltrials.Eventhoughrandomizedtrialsarenotavailable,theremaybeaveryclearclinicalconsensusthataparticulartestortherapyisusefuloreffective.†In2003,the
ACC/AHATaskForceonPracticeGuidelinesdevelopedalistofsuggestedphrasestousewhenwritingrecommendations.Allguidelinerecommendationshavebeenwritteninfullsentencesthatexpress
acompletethought,suchthatarecommendation,evenifseparatedandpresentedapartfromtherestofthedocument(includingheadingsabovesetsofrecommendations),wouldstillconveythe
fullintentoftherecommendation.Itishopedthatthiswillincreasereaders’comprehensionoftheguidelinesandwillallowqueriesattheindividualrecommendationlevel.
recommendations in more than 1 set of guidelines, those 1. Introduction
guidelinesareupdatedconcurrently.
The recommendations in this focused update will be con-
1.1. Evidence Review
sidered current until they are superseded by another focused
update or the full-text guidelines are revised. This focused Late-breaking clinical trials presented at the 2005 and 2006
updateispublishedintheJanuary15,2008,issueoftheJournal annualscientificmeetingsoftheACC,AHA,andEuropean
oftheAmericanCollegeofCardiologyandtheJanuary15,2008, Society of Cardiology, as well as selected other data, were
issueofCirculationasanupdatetothefull-textguidelinesand reviewed by the standing guideline writing committee along
is also posted on the ACC (www.acc.org) and AHA (www. withtheparentTaskForceandotherexpertstoidentifythose
americanheart.org)Websites.Copiesofthefocusedupdateare trialsandotherkeydatathatmightimpactguidelinesrecom-
availablefrombothorganizations. mendations. On the basis of the criteria/considerations noted
above, recent trial data and other clinical information were
considered important enough to prompt a focused update of
Sidney C. Smith, Jr., MD, FACC, FAHA the 2004 ACC/AHA Guidelines for the Management of
Chair, ACC/AHA Task Force on Practice Guidelines PatientsWithST-ElevationMyocardialInfarction[seeChen
Alice K. Jacobs, MD, FACC, FAHA ZM et al. (3); Chen ZM et al. (4); ASSENT-4 PCI (5);
Vice-Chair, ACC/AHA Task Force on Practice Guidelines AntmanEMetal.(6);YusufSetal.(7);BhattDLetal.(8);
214 Antmanetal. JACCVol.51,No.2,2008
STEMIFocusedUpdate January15,2008:210–47
SabatineMSetal.(9);BennettJSetal.(10);SmithSCJret will be incorporated into future revisions and/or updates of
al.(11);OAT(12,13)andTOSCA(14)]. the full-text guidelines.
Whenconsideringthenewdataforthisfocusedupdate,the
writinggroupfacedthetaskofweighingevidencefromstudies 1.2. Organization of Committee and
enrolling large numbers of subjects outside North America. Relationships With Industry
Althoughnotingthatpracticepatternsandtherigorappliedto
For this focused update, all members of the 2004 STEMI
datacollection,aswellasthegeneticmakeupofsubjects,might
writing committee were invited to participate; those who
influence the observed magnitude of a treatment effect, the
agreed (referred to as the 2007 focused update writing
writinggroupbelievedthedatawererelevanttoformulationof
group)wererequiredtodiscloseallRWIrelevanttothedata
recommendationsformanagementofST-elevationmyocardial
under consideration (2). Focused update writing group
infarction (STEMI) in North America. The reasons for this
members who had no significant relevant RWI wrote the
decisionincludethat1)abroadarrayofmanagementstrategies
firstdraftofthefocusedupdate;thedraftwasthenreviewed
was represented, including substantial proportions of subjects
andrevisedbythefullwritinggroup.Eachrecommendation
who received some form of reperfusion therapy, 2) concomi-
required a confidential vote by the writing group members
tanttreatmentswithprovenefficacy(e.g., aspirin, betablock-
before external review of the document. Any writing com-
ers, inhibitors of the renin-angiotensin-aldosterone system,
mittee member with a significant (greater than $10 000)
andstatins)wereusedinthemajorityofpatients,and3)itwas
relationship with industry relevant to the recommendation
considered an impractical expectation that the tens of thou-
was recused from voting on that recommendation.
sandsofpatientswithSTEMIneededtomeettheestimated
sample size for contemporary clinical trials be enrolled exclu-
1.3. Review and Approval
sivelyatNorthAmericansites.
To provide clinicians with a comprehensive set of data, Thisdocumentwasreviewedby3outsidereviewersnominated
whenever possible the exact event rates in various treatment bytheACCand3outsidereviewersnominatedbytheAHA,
armsofclinicaltrialsarepresentedtopermitcalculationofthe as well as 1 reviewer each from the American Academy of
absolute risk difference (ARD) and number needed to treat Family Physicians and the Canadian Cardiovascular Society
(NNT) or harm (NNH); the relative treatment effects are (CCS)and58individualcontentreviewers.AllreviewerRWI
described either as odds ratio (OR), relative risk (RR), or information was collected and distributed to the writing
hazard ratio (HR), depending on the format in the original committeeandispublishedinthisdocument(seeAppendix2
publication. fordetails).
Consultthefull-textversionorexecutivesummaryofthe This document was approved for publication by the
2004 ACC/AHA Guidelines for the Management of Pa- governing bodies of the American College of Cardiology
tients With ST-Elevation Myocardial Infarction (15) for Foundation and the American Heart Association and en-
policy on clinical areas not covered by the focused update. dorsedbytheAmericanAcademyofFamilyPhysiciansand
Individualrecommendationsupdatedinthisfocusedupdate the Canadian Cardiovascular Society.
2. Analgesia
Table2. UpdatestoSection6.3.1.3:Analgesia
2004STEMIGuidelineRecommendation 2007STEMIFocusedUpdateRecommendation Comments
ClassI
Morphinesulfate(2to4mgIVwithincrementsof2to 1.Morphinesulfate(2to4mgIVwithincrementsof2to8mgIV 2004recommendation
8mgIVrepeatedat5-to15-minuteintervals)isthe repeatedat5-to15-minuteintervals)istheanalgesicof remainscurrentin
analgesicofchoiceformanagementofpain choiceformanagementofpainassociatedwithSTEMI.(Level 2007Update
associatedwithSTEMI.(LevelofEvidence:C) ofEvidence:C)
2.PatientsroutinelytakingNSAIDs(exceptforaspirin),both Newrecommendation
nonselectiveaswellasCOX-2selectiveagents,beforeSTEMI
shouldhavethoseagentsdiscontinuedatthetimeof
presentationwithSTEMIbecauseoftheincreasedriskof
mortality,reinfarction,hypertension,heartfailure,andmyocardial
ruptureassociatedwiththeiruse.(LevelofEvidence:C)
ClassIII
1.NSAIDs(exceptforaspirin),bothnonselectiveaswellasCOX-2 Newrecommendation
selectiveagents,shouldnotbeadministeredduring
hospitalizationforSTEMIbecauseoftheincreasedriskof
mortality,reinfarction,hypertension,heartfailure,and
myocardialruptureassociatedwiththeiruse.(Levelof
Evidence:C)
COX-2indicatescyclooxygenase-2;IV,intravenous/intravenously;NSAIDs,nonsteroidalanti-inflammatorydrugs;andSTEMI,ST-elevationmyocardialinfarction.
JACCVol.51,No.2,2008 Antmanetal. 215
January15,2008:210–47 STEMIFocusedUpdate
Analysis of retrospective data (16) has raised a question inhibitors and other nonsteroidal anti-inflammatory drugs
aboutthepotentiallyadverseeffectsofmorphineinpatients (NSAIDs) (17–19), these drugs should be discontinued
with unstable angina (UA)/non–ST-elevation myocardial immediately at the time of STEMI (see 2004 STEMI
infarction(NSTEMI).Asaresult,therecommendationfor Guidelines, Section 7.12.5, for additional discussion)
morphine pain relief has been reduced to a Class IIa (3,15,20,21). A substudy analysis from the ExTRACT
recommendation for that patient population. Use of mor- TIMI-25 (Enoxaparin and Thrombolysis Reperfusion for
phine remains a Class I recommendation for patients with Acute Myocardial Infarction Treatment–Thrombolysis in
STEMI, however, because STEMI patients should either MyocardialInfarction)trial(22)demonstratedanincreased
have received reperfusion or are not candidates for reperfu- risk of death, reinfarction, heart failure, or shock among
sion, and continuing pain requires relief in either case patients who were taking NSAIDs within 7 days of enroll-
(Table 2). ment. Longer-term management considerations and a dis-
Because of the known increased risk of cardiovascular cussionofthegradientofriskwiththevariousNSAIDSare
events among patients taking cyclooxygenase-2 (COX-2) foundinSection7.12.5ofthe2004STEMIGuidelines(15).
3. Beta Blockers
Table3. UpdatestoSection6.3.1.5:BetaBlockers
2004STEMIGuidelineRecommendation 2007STEMIFocusedUpdateRecommendation Comments
ClassI
Oralbeta-blockertherapyshouldbeadministered 1.Oralbeta-blockertherapyshouldbeinitiatedinthefirst24hoursforpatients Modifiedrecommendation
promptlytothosepatientswithouta whodonothaveanyofthefollowing:1)signsofheartfailure,2)evidenceof (changedLOEandtext)
contraindication,irrespectiveofconcomitant alowoutputstate,3)increasedrisk*forcardiogenicshock,or4)other
fibrinolytictherapyorperformanceofprimary relativecontraindicationstobetablockade(PRintervalgreaterthan0.24
PCI.(LevelofEvidence:A) seconds,second-orthird-degreeheartblock,activeasthma,orreactive
airwaydisease).(LevelofEvidence:B)
Patientswithearlycontraindicationswithinthe 2.Patientswithearlycontraindicationswithinthefirst24hoursofSTEMI 2004recommendation
first24hoursofSTEMIshouldbereevaluated shouldbereevaluatedforcandidacyforbeta-blockertherapyassecondary remainscurrentin
forcandidacyforbeta-blockertherapyas prevention.(LevelofEvidence:C) 2007Update
secondaryprevention.(LevelofEvidence:C)
PatientswithmoderateorsevereLVfailure 3.PatientswithmoderateorsevereLVfailureshouldreceivebeta-blocker 2004recommendation
shouldreceivebeta-blockertherapyas therapyassecondarypreventionwithagradualtitrationscheme.(Levelof remainscurrentin
secondarypreventionwithagradualtitration Evidence:B) 2007Update
scheme.(LevelofEvidence:B)
ClassIIa
ItisreasonabletoadministerIVbetablockers 1.ItisreasonabletoadministeranIVbetablockeratthetimeofpresentation Modifiedrecommendation
promptlytoSTEMIpatientswithout toSTEMIpatientswhoarehypertensiveandwhodonothaveanyofthe (changedtext)
contraindications,especiallyifa following:1)signsofheartfailure,2)evidenceofalowoutputstate,3)
tachyarrhythmiaorhypertensionispresent. increasedrisk*forcardiogenicshock,or4)otherrelativecontraindications
(LevelofEvidence:B) tobetablockade(PRintervalgreaterthan0.24seconds,second-orthird-
degreeheartblock,activeasthma,orreactiveairwaydisease).(Levelof
Evidence:B)
ClassIII
1.IVbetablockersshouldnotbeadministeredtoSTEMIpatientswhohaveany Newrecommendation
ofthefollowing:1)signsofheartfailure,2)evidenceofalowoutputstate,
3)increasedrisk*forcardiogenicshock,or4)otherrelative
contraindicationstobetablockade(PRintervalgreaterthan0.24seconds,
second-orthird-degreeheartblock,activeasthma,orreactiveairway
disease).(LevelofEvidence:A)
*Riskfactorsforcardiogenicshock(thegreaterthenumberofriskfactorspresent,thehighertheriskofdevelopingcardiogenicshock)areagegreaterthan70years,systolicbloodpressurelessthan
120mmHg,sinustachycardiagreaterthan110bpmorheartratelessthan60bpm,andincreasedtimesinceonsetofsymptomsofSTEMI.
IVindicatesintravenous;LOE,levelofevidence;LV,leftventricular;PCI,percutaneouscoronaryintervention;andSTEMI,ST-elevationmyocardialinfarction.
The 2004 STEMI Guidelines recommendations (Table 3) following 2 later randomized trials of IV beta blockade
were based on studies that showed a reduced incidence of (23,24), a post-hoc analysis of the use of atenolol in the
subsequent reinfarction and recurrent ischemia in patients GUSTO-I (Global Utilization of Streptokinase and TPA
receivingbothfibrinolytictherapyandintravenous(IV)beta for Occluded Coronary Arteries) trial (25), and a review of
blockers. However, uncertainty about the use of IV beta early beta-blocker therapy in myocardial infarction (MI)
blockers in the setting of fibrinolytic therapy has increased (26)thatdidnotfindsignificantreductionsinmortality(15).
216 Antmanetal. JACCVol.51,No.2,2008
STEMIFocusedUpdate January15,2008:210–47
3.1. COMMIT/CCS-2 (Metoprolol) (Table 3), and these situations are discussed below. It is
reasonabletoadministerIVbeta-blockertherapyonDays0
The COMMIT/CCS-2 (Clopidogrel and Metoprolol in
to 1 of hospitalization for STEMI when hypertension is
Myocardial Infarction Trial/Second Chinese Cardiac
present and the patient is not at an increased risk of
Study) (4) randomized 45 852 patients within 24 hours of
cardiogenic shock on the basis of the risk factors defined
onset of suspected MI to receive metoprolol (up to 3 doses
above. Patients with sinus tachycardia or atrial fibrillation
of5mgIVeachinthefirst15minutes,followedby200mg
shouldhaveleftventricular(LV)functionrapidlyevaluated
orally daily) or matching placebo. Fifteen minutes after the
beforeadministrationofIVbetablockers(orothernegative
IV doses, a 50-mg tablet of metoprolol or placebo was
inotropes, such as non-dihydropyridine calcium channel
administeredorallyandrepeatedevery6hoursduringDays
blockers). From Day 2 onward, when beneficial effects on
0 to 1 of hospitalization. From Day 2 onward, 200 mg of
reinfarctionandventricularfibrillationareseen,administra-
controlled-release metoprolol or placebo was administered
tion of 200 mg of controlled-release oral metoprolol daily
orally daily (this is the Food and Drug Administration
appears to be safe in hemodynamically stable patients with
[FDA]-approved regimen for metoprolol in MI) until
STEMI who are free of contraindications. It is prudent to
dischargefromthehospitaloruptoamaximumof4weeks
initiate a dose of 50 mg of metoprolol orally every 6 hours,
in hospital (in survivors, the mean was 15 days). The 2
transitioning to a dose equivalent to 200 mg per day orally
prespecified co-primary outcomes were the composite of
or the maximum tolerated dose. It should be noted that
death, reinfarction, or cardiac arrest and death from any
long-termuseoforalbetablockersisstronglyrecommended
cause during the scheduled treatment period.
(ClassI,LevelofEvidence:A)forsecondarypreventionin
Neither of the co-primary study end points was signifi-
patients at highest risk, such as those with low ejection
cantly reduced by allocation to metoprolol. For every 1000
fraction, heart failure, or postshock, once they have stabi-
patients treated, allocation to metoprolol was associated
lized,withgradualdosetitration(27)(seethe2004STEMI
with 5 fewer episodes of reinfarction, 5 fewer episodes of
Guidelines, Sections 7.4.1 and 7.12.7) (15).
ventricular defibrillation, but 11 more episodes of cardio-
TheresultsoftheCOMMIT-CCS2trialraisequestions
genic shock. The excess of cardiogenic shock was seen
aboutthesafetyofearlyuseofIVbetablockers,particularly
chiefly from Days 0 to 1 after hospitalization, whereas the
in high-risk populations, and led the writing group to
reductions in reinfarction and ventricular fibrillation ap-
reexamine the overall evidence base for beta-blocker ther-
peared from Day 2 onward.
apy.Theevidencebaseforthistherapywasdevelopedmore
Allocation to metoprolol produced an average relative
than 25 years ago in a treatment environment that differs
increase in cardiogenic shock of 30%, with higher rates for
from contemporary practice. Moreover, no study included
those greater than 70 years of age, or with systolic blood
an oral beta blocker–only arm. The writing group consen-
pressurelessthan120mmHg,orwithpresentingheartrate
sus, however, was not to change the classification of the
greaterthan110bpm,orwithKillipclassgreaterthan1.On
current early oral beta-blocker recommendation but to
average across the whole study population, the absolute
restrict it to patients who are not at high risk for compli-
reduction in arrhythmia-related deaths and the absolute
cations. In addition, because of the absence of a study that
increaseincardiogenicshock–relateddeathswereofsimilar
specifically evaluated oral therapy alone, the Level of Evi-
magnitude.Noapparentdifferencewasnotedbetweenthe2
dence has been changed from A to B. Nevertheless, early
treatment groups in the other attributed causes of death,
(within24hours)oralbeta-blockertherapyremainsaClass
either individually or in aggregate. Metoprolol allocation
I recommendation for those patients who are not at high
was associated with significantly more persistent hypoten-
risk for complications. Whether this change should affect
sion and more cases of bradycardia.
currentperformancemeasuresisbeyondthescopeofthis
Though patients at high or low risk could be identified,
document. The findings of potential risk of beta-blocker
the authors noted that they were not able to identify any
therapy in COMMIT emphasize the importance of
subgroups in which the benefits clearly outweighed the
continually monitoring these patients throughout hospi-
risks.
talization for signs and symptoms of complications of
3.2. Conclusion
therapy, as noted in other sections of the original
Thisfocusedupdateexpandsontheconceptsintroducedin guidelines (Sections 6.3.1.5, 7.4.1, and 7.12.7). Because
the 2004 STEMI Guidelines, underscoring the potential of the uncertainty about the benefit of oral beta blockers
risk of administering IV beta blockers to patients with early on (e.g., in COMMIT-CCS 2, Days 0 to 1), the
severe heart failure or cardiogenic shock. There are several writing group recommends further research and addi-
circumstances in which it can be useful (Class IIa) to tional examination at the time of the next revision to the
administer an IV beta blocker acutely to a STEMI patient STEMI Guidelines.
JACCVol.51,No.2,2008 Antmanetal. 217
January15,2008:210–47 STEMIFocusedUpdate
4. Reperfusion
Table4. UpdatestoSection6.3.1.6:Reperfusion
2004STEMIGuidelineRecommendation 2007STEMIFocusedUpdateRecommendation Comments
ClassI
PrimaryPCIshouldbeperformedasquicklyaspossible 1.STEMIpatientspresentingtoahospitalwithPCIcapabilityshouldbe Modifiedrecommendation
withthegoalofamedicalcontact–to-balloonor treatedwithprimaryPCIwithin90minutesoffirstmedicalcontact (changedLOEandtext)
door-to-balloonintervalofwithin90minutes.(Level (seeFigure1)asasystemsgoal.(LevelofEvidence:A)
ofEvidence:B)
STEMIpatientspresentingtoafacilitywithoutthe 2.STEMIpatientspresentingtoahospitalwithoutPCIcapabilityand Modifiedrecommendation
capabilityforexpert,promptinterventionwith whocannotbetransferredtoaPCIcenterandundergoPCIwithin (changedLOEandtext)
primaryPCIwithin90minutesoffirstmedical 90minutesoffirstmedicalcontact(seeFigure1)shouldbetreated
contactshouldundergofibrinolytictherapyunless withfibrinolytictherapywithin30minutesofhospitalpresentation
contraindicated.(LevelofEvidence:A) asasystemsgoalunlessfibrinolytictherapyiscontraindicated.
(LevelofEvidence:B)
PCIindicatesprimarycoronaryintervention;LOE,levelofevidence;andSTEMI,ST-elevationmyocardialinfarction.
4.1. Logistics of Care laboratoryoranatomicalchallenges(issuesofarterial,coronary,
or lesion access) that prolong the PCI procedure. In the
Regardlessofthemodeofreperfusion,theoverarchingconcept
absenceofsuchcircumstances,however,reperfusionshouldbe
istominimizetotalischemictime,whichisdefinedasthetime
achieved as soon as possible within this time, and many
fromonsetofsymptomsofSTEMItoinitiationofreperfusion
hospitals with refined systems are approaching median door-
therapy.Itisincreasinglyclearthat2typesofhospitalsystems
to-balloon times of 60 to 70 minutes. Discussions about
providereperfusiontherapy:thosewithpercutaneouscoronary
intervention(PCI)capabilityandthosewithoutPCIcapabil- measurement,particularlywithrespecttoinclusioncriteriaand
ity. When PCI capability is available, the best outcomes are the appropriate time to end measurement, are beyond the
achievedbyofferingthisstrategy24hoursperday,7daysper scope of this document and are being considered by groups
week(28).Thesystemsgoalshouldbeafirstmedicalcontact– that are focusing on how to improve the alignment between
to-balloontimewithin90minutes(Table4,Figure1).There what is measured and patient outcomes. The focus on mea-
should be an ongoing program of outcomes analysis and surement should not displace the emphasis on improving
periodic case review to identify process-of-care strategies that processes that will facilitate more rapid treatment that is
willcontinuallyimprovetimetotreatmentandfacilitaterapid deliveredsafelyandappropriately.Thiscommitteecontinues
and appropriate treatment. A comprehensive effort in this toendorsetheconceptthatfastertimestoreperfusionand
regard is the AHA Mission Lifeline program, a community- bettersystemsofcareareassociatedwithimportantreductions
based national initiative to improve the quality of care and inmorbidityandmortalityratesinpatientswithSTEMI.An
outcomes of patients with STEMI by improving health care underutilized but effective strategy for improving systems of
system readiness and response to STEMI (29). The “Door- careforSTEMIpatientsistoexpandtheuseofprehospital
to-Balloon (D2B): An Alliance for Quality” campaign 12-lead electrocardiography programs by emergency medical
(www.d2balliance.org),launchedbytheACCincollaboration systems(EMS)thatprovideadvancedlifesupport(33,34).
withmanyorganizations,includingtheAHA,aimstoimprove The emphasis on primary PCI should not obscure the
the timeliness of primary PCI. The goal is to increase the importance of fibrinolytic therapy. Many hospital systems in
percentageofpatientswhoreceivetimelyprimaryPCI,withan NorthAmericadonothavethecapabilityofmeetingthetime
emphasisonhavingatleast75%ofpatientstreatedwithin90 goal for primary PCI (35). Therefore, because of the critical
minutes of presentation at the hospital, with a recommenda- importance of time to treatment from onset of symptoms of
tionfortheuseofevidence-basedstrategiestoreduceneedless STEMI in reducing morbidity and mortality, fibrinolytic
delays (30). The 75% goal was set in recognition that some therapyispreferred.Inthesesettings,transferprotocolsneedtobe
patients have clinically relevant non–system-based delays that inplaceforarrangingrescuePCIwhenclinicallyindicated(36).
do not represent quality-of-care issues. In hospitals without For fibrinolytic therapy, the system goal is to deliver the
PCI capability, immediate transfer for primary PCI is a drugwithin30minutesofthetimethatthepatientpresentsto
treatment option when the expected door-to-balloon time is thehospital(Table4).ThefocusforprimaryPCIisfromfirst
within90minutesoffirstmedicalcontact(31,32). medicalcontactbecauseinregionalizationstrategies,extratime
It is important to note that the door-to-balloon goal is a maybetakentotransportpatientstoacenterthatperformsthe
systems goal that may not be possible to achieve for an procedure.Consequently,itisimportanttoconsiderthetime
individual patient because of patient variables (uncertainty fromfirstmedicalcontact.Thewritinggroupdoesbelievethat
about diagnosis, evaluation and treatment of other life- every effort should be made to reduce the time from first
threateningconditions,obtaininginformedconsent,etc.)that medicalcontacttofibrinolytictherapywhenthatisconsidered
delay the patient’s arrival in the interventional cardiology theappropriatereperfusionstrategy.
218 Antmanetal. JACCVol.51,No.2,2008
STEMIFocusedUpdate January15,2008:210–47
Figure1. OptionsforTransportationofSTEMIPatientsandInitialReperfusionTreatmentGoals
ReperfusioninpatientswithSTEMIcanbeaccomplishedbypharmacological(fibrinolysis)orcatheter-based(primaryPCI)approaches.Theoverarchinggoalistokeeptotal
ischemictimewithin120minutes(ideallywithin60minutes)fromsymptomonsettoinitiationofreperfusiontreatment.Withinthiscontext,thefollowingaregoalsforthemed-
icalsystem*basedonthemodeofpatienttransportationandthecapabilitiesofthereceivinghospital:
MedicalSystemGoals:EMSTransport(Recommended):
•IfEMShasfibrinolyticcapabilityandthepatientqualifiesfortherapy,prehospitalfibrinolysisshouldbestartedwithin30minutesofarrivalofEMSonthescene.
•IfEMSisnotcapableofadministeringprehospitalfibrinolysisandthepatientistransportedtoanon–PCI-capablehospital,thedoor-to-needletimeshouldbewithin30minutes
forpatientsforwhomfibrinolysisisindicated.
•IfEMSisnotcapableofadministeringprehospitalfibrinolysisandthepatientistransportedtoaPCI-capablehospital,theEMSarrival-to-balloontimeshouldbewithin90minutes.
•IfEMStakesthepatienttoanon–PCI-capablehospital,itisappropriatetoconsideremergencyinterhospitaltransferofthepatienttoaPCI-capablehospitalformechanical
revascularizationif
XThereisacontraindicationtofibrinolysis.
XPCIcanbeinitiatedpromptlywithin90minutesfromEMSarrival-to-balloontimeatthePCI-capablehospital.†
XFibrinolysisisadministeredandisunsuccessful(i.e.,“rescuePCI”).
PatientSelf-Transport(Discouraged):
•Ifthepatientarrivesatanon–PCI-capablehospital,thedoor-to-needletimeshouldbewithin30minutesofarrivalattheemergencydepartment.
•IfthepatientarrivesataPCI-capablehospital,thedoor-to-balloontimeshouldbewithin90minutes.
•Ifthepatientpresentstoanon–PCI-capablehospital,itisappropriatetoconsideremergencyinterhospitaltransferofthepatienttoaPCI-capablehospitalif
XThereisacontraindicationtofibrinolysis.
XPCIcanbeinitiatedwithin90minutesafterthepatientpresentedtotheinitialreceivinghospitalorwithin60minutescomparedwithwhenfibrinolysiswithafibrin-specific
agentcouldbeinitiatedattheinitialreceivinghospital.
XFibrinolysisisadministeredandisunsuccessful(i.e.,“rescuePCI”).
*ThemedicalsystemgoalistofacilitaterapidrecognitionandtreatmentofpatientswithSTEMIsothatdoor-to-needle(ormedicalcontact-to-needle)forinitiationoffibrinolytic
therapycanbeachievedwithin30minutesordoor-to-balloon(ormedicalcontact-to-balloon)forPCIcanbeachievedwithin90minutes.Thesegoalsshouldnotbeunderstoodas
“ideal”timesbutratherthelongesttimesthatshouldbeconsideredacceptableforagivensystem.Systemsthatareabletoachieveevenmorerapidtimesfortreatmentof
patientswithSTEMIshouldbeencouraged.Note“medicalcontact”isdefinedas“timeofEMSarrivalonscene”afterthepatientcallsEMS/9-1-1or“timeofarrivalatthe
emergencydepartmentdoor”(whetherPCI-capableornon–PCI-capablehospital)whenthepatienttransportshimself/herselftothehospital.
†EMSArrival¡Transporttonon–PCI-capablehospital¡Arrivalatnon–PCI-capablehospitaltotransfertoPCI-capablehospital¡ArrivalatPCI-capablehospital-to-balloontime(cid:1)90
minutes.
EMSindicatesemergencymedicalsystem;PCI,percutaneouscoronaryintervention;andSTEMI,ST-elevationmyocardialinfarction.
Modifiedwithpermissionfrom(90)andfrom(15).
JACCVol.51,No.2,2008 Antmanetal. 219
January15,2008:210–47 STEMIFocusedUpdate
5. Facilitated PCI
Table5. UpdatestoSection6.3.1.6.4.4:FacilitatedPCI
2004STEMIGuideline
Recommendation 2007STEMIFocusedUpdateRecommendation Comments
ClassIIb
FacilitatedPCImightbeperformedasa 1.FacilitatedPCIusingregimensotherthanfull-dosefibrinolytictherapymightbe Modifiedrecommendation
reperfusionstrategyinhigher-risk consideredasareperfusionstrategywhenallofthefollowingarepresent: (changedLOEandtext)
patientswhenPCIisnotimmediately a.Patientsareathighrisk,b.PCIisnotimmediatelyavailablewithin90
availableandbleedingriskislow. minutes,andc.Bleedingriskislow(youngerage,absenceofpoorlycontrolled
(LevelofEvidence:B) hypertension,normalbodyweight).(LevelofEvidence:C)
ClassIII
1.Aplannedreperfusionstrategyusingfull-dosefibrinolytictherapyfollowedby Newrecommendation
immediatePCImaybeharmful.(LevelofEvidence:B)
LOEindicateslevelofevidence;PCI,percutaneouscoronaryintervention,andSTEMI,ST-elevationmyocardialinfarction.
Facilitated PCI refers to a strategy of planned immediate botic therapy suboptimal for the facilitated PCI group.
PCI after administration of an initial pharmacological Moreover,themediantreatmentdelaybetweenadministra-
regimen intended to improve coronary patency before the tion of tenecteplase and PCI was only 104 minutes, and
procedure. These regimens have included high-dose hepa- mortalityrateswerehigherinPCIcenters.Theevidenceon
rin,plateletglycoprotein(GP)IIb/IIIainhibitors,full-dose whether earlier (prehospital) administration of fibrinolytic
orreduced-dosefibrinolytictherapy,andthecombinationof therapy, better antithrombotic therapy, longer delays to
a GP IIb/IIIa inhibitor with a reduced-dose fibrinolytic PCI,orselectiveuseofPCIasarescuestrategywouldmake
agent (e.g., fibrinolytic dose typically reduced 50%). Facil- the facilitated PCI strategy beneficial is unclear. These
itated PCI should be differentiated from primary PCI issues require further study. On the basis of these data,
without fibrinolytic therapy, from primary PCI with a GP however, facilitated PCI offered no clinical benefit.
IIb/IIIa inhibitor started at the time of PCI, from early or
Keeleyandcoworkersperformedaquantitativereviewof
delayed PCI after successful fibrinolytic therapy, and from
17 trials that compared facilitated PCI with primary PCI
rescuePCIafterunsuccessfulfibrinolytictherapy.Potential
(38) (Figure 2). Nine trials involved GP IIb/IIIa inhibitors
advantages of facilitated PCI include earlier time to reper- alone(n(cid:1)1148),6trialswithfibrinolytictherapy(including
fusion,smallerinfarctsize,improvedpatientstability,lower ASSENT-4PCI)(n(cid:1)2953),and2trialswithafibrinolytic
infarct artery thrombus burden, greater procedural success agentplusaGPIIb/IIIainhibitor(n(cid:1)399).FacilitatedPCI
rates,higherTIMI(ThrombolysisinMyocardialInfarction
with fibrinolytic therapy had significantly higher rates of
trial)flowrates,andimprovedsurvivalrates.Potentialrisks
mortality, nonfatal reinfarction, urgent target-vessel revas-
includeincreasedbleedingcomplications,especiallyinolder
cularization,totalandhemorrhagicstroke,andmajorbleed-
patients. Potential limitations include additional cost (37).
ingcomparedwithprimaryPCI.Therewerenodifferences
Despite the potential advantages, clinical trials of facili-
inefficacyorsafetywhenfacilitatedPCIwithaGPIIb/IIIa
tated PCI have not demonstrated any benefit in reducing
inhibitor was compared with primary PCI.
infarctsizeorimprovingoutcomes.Thelargestofthesewas
Aplannedreperfusionstrategyusingfull-dosefibrinolytic
theASSENT-4PCI(AssessmentoftheSafetyandEfficacy
therapyfollowedbyimmediatePCImaybeharmful(Table
of a New Treatment Strategy with Percutaneous Coronary
5).Nevertheless,selectiveuseofthefacilitatedstrategywith
Intervention)trial(5),inwhich1667patientswererandom-
regimens other than full-dose fibrinolytic therapy in sub-
ized to receive full-dose tenecteplase and PCI versus pri-
groupsofpatientsathighrisk(largeMIorhemodynamicor
maryPCI.Thetrialwasterminatedprematurelybecauseof
electrical instability) with low risk of bleeding who present
a higher in-hospital mortality rate in the facilitated PCI
group (6% vs. 3%; p(cid:1)0.01). The primary end point, a to hospitals without PCI capability might be performed
composite of death, shock, and congestive heart failure when transfer delays for primary PCI are anticipated.
within90days,wassignificantlyhigherwithfacilitatedPCI Although quantitative analysis showed no advantage for
than with primary PCI (18.6% vs. 13.4%; p(cid:1)0.0045), and pretreatment with a GP IIb/IIIa inhibitor, it did not
there was a trend toward a higher 90-day mortality rate document any major disadvantage either. The use of GP
(6.7% vs. 4.9%; p(cid:1)0.14). Defenders of the facilitated PCI IIb/IIIa inhibitors, particularly abciximab, during primary
strategypointoutthattheabsenceofaninfusionofheparin PCI is well established (55). Further trials of reduced-dose
afterbolusadministrationandtheabsenceofaloadingdose fibrinolytictherapy,withorwithoutGPIIb/IIIainhibitors,
of clopidogrel, plus prohibition of GP IIb/IIIa inhibitors areinprogressandmayyielddifferentefficacyand/orsafety
except in bail-out situations, made adjunctive antithrom- results.