2009 Focused Updates: ACC/AHA Guidelines for the

39 Pages·2010·0.73 MB·English

2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With
ST-Elevation Myocardial Infarction (Updating the 2004 Guideline and 2007 Focused
Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention
(Updating the 2005 Guideline and 2007 Focused Update) : A Report of the American
College of Cardiology Foundation/American Heart Association Task Force on Practice
Guidelines
Frederick G. Kushner, Mary Hand, Sidney C. Smith, Jr, Spencer B. King III, Jeffrey L.
Anderson, Elliott M. Antman, Steven R. Bailey, Eric R. Bates, James C. Blankenship, Donald E.
Casey, Jr, Lee A. Green, Judith S. Hochman, Alice K. Jacobs, Harlan M. Krumholz, Douglass
A. Morrison, Joseph P. Ornato, David L. Pearle, Eric D. Peterson, Michael A. Sloan, Patrick L.
Whitlow and David O. Williams
Circulation. 2009;120:2271-2306; originally published online November 18, 2009;
doi: 10.1161/CIRCULATIONAHA.109.192663
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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AHA Scientific Statement
2009 Focused Updates: ACC/AHA Guidelines for the
Management of Patients With ST-Elevation Myocardial
Infarction (Updating the 2004 Guideline and 2007 Focused
Update) and ACC/AHA/SCAI Guidelines on Percutaneous
Coronary Intervention (Updating the 2005 Guideline and 2007
Focused Update)
A Report of the American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines
Frederick G. Kushner, MD, FACC, FAHA, FSCAI, Co-Chair; Mary Hand, MSPH, RN, FAHA, Co-Chair*;
Sidney C. Smith, Jr, MD, FACC, FAHA, Chair; Spencer B. King III, MD, MACC, FSCAI, Co-Chair;
Jeffrey L. Anderson, MD, FACC, FAHA; Elliott M. Antman, MD, FACC, FAHA;
Steven R. Bailey, MD, FACC, FSCAI; Eric R. Bates, MD, FACC, FAHA;
James C. Blankenship, MD, FACC, FSCAI; Donald E. Casey, Jr, MD, MPH, MBA;
Lee A. Green, MD, MPH; Judith S. Hochman, MD, FACC, FAHA;
Alice K. Jacobs, MD, FACC, FAHA, FSCAI; Harlan M. Krumholz, MD, SM, FACC, FAHA;
Douglass A. Morrison, MD, PhD, FACC, FSCAI; Joseph P. Ornato, MD, FACC, FAHA;
David L. Pearle, MD, FACC, FAHA; Eric D. Peterson, MD, MPH, FACC, FAHA;
Michael A. Sloan, MD, MS, FACC, FAHA; Patrick L. Whitlow, MD, FACC, FAHA;
David O. Williams, MD, FACC, FAHA, FSCAI
*TheopinionsexpressedinthisarticleshouldnotbeconstruedasnecessarilyrepresentinganofficialpositionoftheUSDepartmentofHealthandHumanServices,
theAgencyforHealthcareResearchandQuality,ortheUSGovernment,bywhomM.Handisemployed.
†RecusedfromSection3,Thienopyridines;Section4,ParenteralAnticoagulants;Section5,TriageandTransferforPCI.
‡RecusedfromSection3,Thienopyridines;Section4,ParenteralAnticoagulants.
§RecusedfromSection6,IntensiveGlucoseControl.
(cid:1)RecusedfromSection2,GlycoproteinIIb/IIIaReceptorAntagonists;Section3,Thienopyridines.
¶RecusedfromSection3,Thienopyridines.
#RecusedfromSection3,Thienopyridines;Section7,ThrombusAspiration;Section8,UseofStents;Section11,PCIforLeftMainCoronaryArteryDisease.
**RecusedfromSection3,Thienopyridines.
††SocietyforCardiovascularAngiographyandInterventionsRepresentative.
‡‡RecusedfromSection10,FractionalFlowReserve.
§§RecusedfromSection3,Thienopyridines;Section5,TriageandTransferforPCI;Section8,UseofStents.
(cid:1)(cid:1)FormerTaskForcememberduringthiswritingeffort.
ThisdocumentwasapprovedbytheAmericanCollegeofCardiologyFoundationBoardofTrusteesinSeptember2009,bytheAmericanHeartAssociation
ScienceAdvisoryandCoordinatingCommitteeinSeptember2009,andbytheSocietyforCardiovascularAngiographyandInterventionsBoardofTrusteesinOctober
2009.
TheAmericanHeartAssociationrequeststhatthisdocumentbecitedasfollows:KushnerFG,HandM,SmithSCJr,KingSB3rd,AndersonJL,
AntmanEM,BaileySR,BatesER,BlankenshipJC,CaseyDJJr,GreenLA,HochmanJS,JacobsAK,KrumholzHM,MorrisonDA,OrnatoJP,Pearle
DL,PetersonED,SloanMA,WhitlowPL,WilliamsDO.2009Focusedupdates:ACC/AHAguidelinesforthemanagementofpatientswithST-elevation
myocardialinfarction(updatingthe2004guidelineand2007focusedupdate)andACC/AHA/SCAIguidelinesonpercutaneouscoronaryintervention
(updatingthe2005guidelineand2007focusedupdate):areportoftheAmericanCollegeofCardiologyFoundation/AmericanHeartAssociationTask
ForceonPracticeGuidelines.Circulation.2009;120:2271–2306.
ThisarticlehasbeencopublishedintheJournaloftheAmericanCollegeofCardiologyandCatheterizationandCardiovascularInterventions.
Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.acc.org), the American Heart
Association (my.americanheart.org), and the Society for Cardiovascular Angiography and Interventions (scai.org). A copy of the document is also
availableathttp://www.americanheart.org/presenter.jhtml?identifier(cid:1)3003999byselectingeitherthe“topiclist”linkorthe“chronologicallist”link(No.
KJ-0734).Topurchaseadditionalreprints,[email protected].
ExpertpeerreviewofAHAScientificStatementsisconductedattheAHANationalCenter.FormoreonAHAstatementsandguidelinesdevelopment,
visithttp://www.americanheart.org/presenter.jhtml?identifier(cid:1)3023366.
Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express
permission of the American Heart Association. Instructions for obtaining permission are located at http://www.americanheart.org/presenter.jhtml?
identifier(cid:1)4431.Alinktothe“PermissionRequestForm”appearsontherightsideofthepage.
(Circulation.2009;120:2271-2306.)
©2009AmericanCollegeofCardiologyFoundationandAmericanHeartAssociation,Inc.
Circulationisavailableathttp://circ.ahajournals.org DOI:10.1161/CIRCULATIONAHA.109.192663
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2272 Circulation December 1, 2009
STEMI WRITING GROUP MEMBERS
Frederick G. Kushner, MD, FACC, FAHA, FSCAI, Co-Chair; Mary Hand, MSPH, RN, FAHA, Co-Chair*;
Elliott M. Antman, MD, FACC, FAHA†; Eric R. Bates, MD, FACC, FAHA‡;
Donald E. Casey, Jr, MD, MPH, MBA; Lee A. Green, MD, MPH§;
Judith S. Hochman, MD, FACC, FAHA(cid:1); Harlan M. Krumholz, MD, SM, FACC, FAHA;
Joseph P. Ornato, MD, FACC, FAHA¶; David L. Pearle, MD, FACC, FAHA;
Michael A. Sloan, MD, MS, FACC, FAHA; Sidney C. Smith, Jr, MD, FACC, FAHA
PCI WRITING GROUP MEMBERS
Sidney C. Smith, Jr, MD, FACC, FAHA, Chair; Spencer B. King III, MD, MACC, FSCAI, Co-Chair#;
Jeffrey L. Anderson, MD, FACC, FAHA**; Steven R. Bailey, MD, FACC, FSCAI††‡‡;
James C. Blankenship, MD, FACC, FSCAI††; Alice K. Jacobs, MD, FACC, FAHA, FSCAI§§;
Douglass A. Morrison, MD, PhD, FACC, FSCAI††; Eric D. Peterson, MD, MPH, FACC, FAHA**;
Patrick L. Whitlow, MD, FACC, FAHA; David O. Williams, MD, FACC, FAHA, FSCAI**
ACCF/AHA TASK FORCE MEMBERS
Alice K. Jacobs, MD, FACC, FAHA, Chair 2009–2011; Sidney C. Smith, Jr, MD, FACC, FAHA,
Immediate Past Chair 2006–2008(cid:1)(cid:1); Jeffrey L. Anderson, MD, FACC, FAHA, Vice Chair;
Christopher E. Buller, MD, FACC; Mark A. Creager, MD, FACC, FAHA;
Steven M. Ettinger, MD, FACC; Robert A. Guyton, MD, FACC, FAHA;
Jonathan L. Halperin, MD, FACC, FAHA; Harlan M. Krumholz, MD, SM, FACC, FAHA(cid:1)(cid:1);
Frederick G. Kushner, MD, FACC, FAHA; Rick Nishimura, MD, FACC, FAHA(cid:1)(cid:1);
Richard L. Page, MD, FACC, FAHA(cid:1)(cid:1); Lynn G. Tarkington, RN;
William G. Stevenson, MD, FACC, FAHA; Clyde W. Yancy, MD, FACC, FAHA
Table of Contents 8. RecommendationsfortheUseofStentsinSTEMI. .2288
8.1. Stent Selection for STEMI. . . . . . . . . ..2288
2009 STEMI and PCI Focused Updates. . . . . . . ..2273 PCI Focused Update Section. . . . . . . . . . . . . ..2289
Preamble . . . . . . . . . . . . . . . . . . . . . . . ..2273 9. Recommendation for Angiography in Patients
1. Introduction . . . . . . . . . . . . . . . . . . . ..2274 With Chronic Kidney Disease. . . . . . . . . . ..2289
1.1. Methodology and Evidence Review . . . . ..2274 9.1. AngiographyinPatientsWithChronic
1.2. Organization of Committee and Relationships KidneyDisease. . . . . . . . . . . . . . . . . .2289
With Industry and Other Entities. . . . . . ..2275 10. Recommendations for Use of Fractional
1.3. Document Review and Approval. . . . . . ..2275 Flow Reserve. . . . . . . . . . . . . . . . . . . ..2289
STEMI and PCI Focused Update Section. . . . . . ..2276 10.1. Fractional Flow Reserve. . . . . . . . . . ..2289
2. Recommendations for the Use of 11. Recommendations for PCI for Unprotected
Glycoprotein IIb/IIIa Receptor Antagonists. . . ..2276 Left Main Coronary Artery Disease. . . . . . . ..2290
2.1. Glycoprotein IIb/IIIa Receptor Antagonists . .2276 11.1. Unprotected Left Main Coronary
3. RecommendationsfortheUseofThienopyridines . .2277 Artery Disease. . . . . . . . . . . . . . . ..2290
3.1. Thienopyridines. . . . . . . . . . . . . . . ..2277 12. Recommendations for the Timing of Angiography
3.1.1. AdditionalThienopyridineInformation. .2280 and Antiplatelet Therapy in UA/NSTEMI . . . ..2292
3.1.2. Choice of Thienopyridine for PCI 12.1. Timing of Angiography. . . . . . . . . . ..2292
in STEMI . . . . . . . . . . . . . . ..2281 12.2. Timing of GP IIb/IIIa Receptor Antagonist
3.2. Proton Pump Inhibitors and Therapy in UA/NSTEMI Patients
Dual-Antiplatelet Therapy for ACS . . . . ..2281 Undergoing Angiography . . . . . . . . . ..2292
4. Recommendations for the Use of Appendix 1. Author Relationships With Industry and
Parenteral Anticoagulants . . . . . . . . . . . . ..2282 Other Entities—ST-Elevation Myocardial
4.1. Parenteral Anticoagulants. . . . . . . . . . ..2282 Infarction . . . . . . . . . . . . . . . ..2294
5. RecommendationsforTriageandTransferforPCI . . .2283 Appendix 2. AuthorRelationshipsWithIndustryand
5.1. Triage and Transfer for PCI . . . . . . . . ..2283 OtherEntities—PercutaneousCoronary
5.1.1. STEMI Patients Who Are Candidates Intervention . . . . . . . . . . . . . . . . ..2295
for Reperfusion . . . . . . . . . . . ..2283 Appendix 3.Reviewer Relationships With Industry
6. Recommendations for Intensive Glucose and Other Entities—2009 STEMI and
Control in STEMI . . . . . . . . . . . . . . . . ..2286 PCI Focused Updates . . . . . . . . . ..2296
6.1. Intensive Glucose Control . . . . . . . . . ..2286 Appendix 4. DosingTableforAntiplateletandAnticoagulant
7. Recommendation for Thrombus Aspiration TherapyDiscussedinThisFocused
During PCI for STEMI . . . . . . . . . . . . . ..2287 UpdatetoSupportPCIinSTEMI . . . . ..2299
7.1. Thrombus Aspiration . . . . . . . . . . . . ..2287 Appendix 5. Triage and Transfer for PCI . . . . . ..2301
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Kushner et al 2009 Focused Updates: STEMI and PCI Guidelines 2273
Appendix 6. OutcomesofPCIVersusCABGfor sizeofthetreatmenteffectandanestimateofthecertaintyof
UnprotectedLeftMainCoronary the treatment effect. Note that a recommendation with level
ArteryDisease . . . . . . . . . . . . . . ..2301 of evidence B or C does not imply that the recommendation
References . . . . . . . . . . . . . . . . . . . . . . ..2302 is weak. Many important clinical questions addressed in
guidelinesdonotlendthemselvestoclinicaltrials.Although
2009 STEMI and PCI Focused Updates
randomized trials may not be available, there may be a very
Preamble clear clinical consensus that a particular test or therapy is
A primary challenge in the development of clinical practice useful and effective. Both the classification of recommenda-
guidelines is keeping pace with the stream of new data on tions and level of evidence listed in the focused updates are
which recommendations are based. In an effort to respond basedonconsiderationoftheevidencereviewedinprevious
promptly to new evidence, the American College of Cardi- iterations of the guideline and the focused update. Of note,
ologyFoundation/AmericanHeartAssociation(ACCF/AHA) the implications of older studies that have informed recom-
Task Force on Practice Guidelines has created a “focused mendations but have not been repeated in contemporary
update” process to revise the existing guideline recommen- settings are considered carefully.
dationsthatareaffectedbyevolvingdataoropinion.Before TheACCF/AHApracticeguidelinesaddresspatientpopula-
the initiation of this focused approach, periodic updates and tions(andhealthcareproviders)residinginNorthAmerica.As
revisions of existing guidelines required up to 3 years to such,drugsthatarenotcurrentlyavailableinNorthAmericaare
complete. Now, however, new evidence will be reviewed in discussedinthetextwithoutaspecificclassofrecommendation.
an ongoing fashion to more efficiently respond to important For studies performed in large numbers of subjects outside of
science and treatment trends that could have a major impact NorthAmerica,eachwritinggroupreviewsthepotentialimpact
on patient outcomes and quality of care. Evidence will be of different practice patterns and patient populations on the
reviewedatleasttwiceayear,andupdateswillbeinitiatedon treatmenteffectandontherelevancetotheACCF/AHAtarget
anas-neededbasisasquicklyaspossible,whilemaintaining population to determine whether the findings should inform a
the rigorous methodology that the ACCF and AHA have specificrecommendation.
developed during their 25 years of partnership. TheACCF/AHApracticeguidelinesareintendedtoassist
These updated guideline recommendations reflect a con- healthcare providers in clinical decision making by describ-
sensusofexpertopinionafterathoroughreviewprimarilyof ing a range of generally acceptable approaches for the
diagnosis, management, and prevention of specific diseases
late-breaking clinical trials identified through a broad-based
orconditions.Theguidelinesattempttodefinepracticesthat
vetting process as being important to the relevant patient
meet the needs of most patients in most circumstances. The
population,aswellasareviewofothernewdatadeemedto
ultimatejudgmentregardingcareofaparticularpatientmust
haveanimpactonpatientcare(seeSection1.1,Methodology
bemadebythehealthcareproviderandpatientinlightofall
andEvidenceReview,fordetails).Thisfocusedupdateisnot
the circumstances presented by that patient. Thus, there are
intended to represent an update based on a full literature
circumstancesinwhichdeviationsfromtheseguidelinesmay
review from the date of the previous guideline publication.
beappropriate.Clinicaldecisionmakingshouldconsiderthe
Specific criteria/considerations for inclusion of new data
qualityandavailabilityofexpertiseintheareawherecareis
include the following:
provided. These guidelines may be used as the basis for
● publication in a peer-reviewed journal; regulatory or payer decisions, but the ultimate goals are
● large randomized, placebo-controlled trial(s); quality of care and serving the patient’s best interests.
● nonrandomized data deemed important on the basis of Prescribed courses of treatment in accordance with these
resultsthataffectcurrentsafetyandefficacyassumptions; recommendations are effective only if they are followed by
● strength/weakness of research methodology and findings; the patient. Because a lack of patient adherence may ad-
● likelihoodofadditionalstudiesinfluencingcurrentfindings; versely affect treatment outcomes, healthcare providers
● impact on current performance measure(s) and/or likeli- should engage the patient in active participation with the
hood of need to develop new performance measure(s); prescribed treatment.
● requests and requirements for review and update from the TheACCF/AHATaskForceonPracticeGuidelinesmakes
practice community, key stakeholders, and other sources every effort to avoid actual, potential, or perceived conflicts
free of relationships with industry or other potential bias; ofinterestthatmayariseasaresultofindustryrelationships
● number of previous trials showing consistent results; and or personal interests among the writing committee. Specifi-
● needforconsistencywithanewguidelineorguidelinerevision. cally, all members of the writing committee, as well as
reviewers of the document, are asked to disclose all such
In analyzing the data and developing updated recommen- relevant relationships pertaining to the trials and other evi-
dationsandsupportingtext,thefocusedupdatewritinggroup dence under consideration (see Appendixes 1, 2, and 3). All
usedevidence-basedmethodologiesdevelopedbytheACCF/ guidelinerecommendationsrequireaconfidentialvotebythe
AHATaskForceonPracticeGuidelines,whicharedescribed writing group and must be approved by a consensus of the
elsewhere.1 members voting. Members who recused themselves from
The schema for classification of recommendations and votingarenotedonthetitlepageofthisdocument.Members
level of evidence is summarized in Table 1, which also mustrecusethemselvesfromvotingonanyrecommendations
illustrateshowthegradingsystemprovidesanestimateofthe to which their relationships with industry and other entities
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2274 Circulation December 1, 2009
Table1. ApplyingClassificationofRecommendationsandLevelofEvidence
*Dataavailablefromclinicaltrialsorregistriesabouttheusefulness/efficacyindifferentsubpopulations,suchasgender,age,historyofdiabetes,historyofprior
myocardialinfarction,historyofheartfailure,andprioraspirinuse.ArecommendationwithLevelofEvidenceBorCdoesnotimplythattherecommendationisweak.
Manyimportantclinicalquestionsaddressedintheguidelinesdonotlendthemselvestoclinicaltrials.Eventhoughrandomizedtrialsarenotavailable,theremay
beaveryclearclinicalconsensusthataparticulartestortherapyisusefuloreffective.
†In 2003, the ACCF/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline
recommendationshavebeenwritteninfullsentencesthatexpressacompletethought,suchthatarecommendation,evenifseparatedandpresentedapartfrom
therestofthedocument(includingheadingsabovesetsofrecommendations),wouldstillconveythefullintentoftherecommendation.Itishopedthatthiswill
increasereaders’comprehensionoftheguidelinesandwillallowqueriesattheindividualrecommendationlevel.
apply.Writinggroupmemberswhodidnotparticipatearenot focused update or the full-text guidelines are revised. This
listed as authors of this focused update. The work of the focusedupdateispublishedintheDecember1,2009,issues
writing group was supported exclusively by the ACCF and of the Journal of the American College of Cardiology and
AHA without commercial support. Writing group members Circulation as an update to the full-text guideline, and it is
volunteered their time for this effort. also posted on the American College of Cardiology (ACC;
With the exception of the recommendations presented here, www.acc.org),AHA(my.americanheart.org),andSocietyfor
the full-text guidelines remain current.2,3 Only the recommen- Cardiovascular Angiography and Interventions (SCAI;
dationsfromtheaffectedsection(s)ofthefull-textguidelinesare
scai.org) World Wide Web sites.
included in this focused update. Recommendations from any
Alice K. Jacobs, MD, FACC, FAHA
section of a guideline affected by a change are presented with
Chair, ACCF/AHA Task Force on Practice Guidelines
notation as to whether they are new or have been modified;
however, recommendations that remain unchanged in each
1. Introduction
sectionarenotincludedinthisfocusedupdate.Whenevidence
affectsrecommendationsinmorethan1setofguidelines,those 1.1. Methodology and Evidence Review
guidelinesareupdatedconcurrentlywheneverpossible. Late-breaking clinical trials presented at the 2007 and 2008
The recommendations in this focused update will be annual scientific meetings of the ACC, AHA, Transcatheter
considered current until they are superseded by another CardiovascularTherapeutics,theEuropeanSocietyofCardi-
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Kushner et al 2009 Focused Updates: STEMI and PCI Guidelines 2275
ology, and the 2009 annual scientific sessions of the ACC America. The writing group also notes that the AHA/ACCF
were reviewed by the standing guideline writing committee and the Heart Rhythm Society have published updated
alongwiththeparentTaskForceandotherexpertstoidentify recommendationsforthestandardizationandinterpretationof
those trials and other key data that may impact guideline the electrocardiogram with a separate section on acute
recommendations. On the basis of the criteria/considerations ischemia/infarction.24
notedabove,recenttrialdataandotherclinicalinformationwere To provide clinicians with a comprehensive set of data,
consideredimportantenoughtopromptafocusedupdateofthe wheneverpossible,theexacteventratesinvarioustreatment
ACC/AHA 2004 Guidelines for the Management of Patients arms of clinical trials are presented to permit calculation of
With ST-Elevation Myocardial Infarction and the ACC/AHA the absolute risk difference and number needed to treat
2005GuidelinesforPercutaneousCoronaryIntervention,inclu- (NNT) or harm; the relative treatment effects are described
siveoftheirrespective2007focusedupdates.2–5 either as odds ratio, relative risk (RR), or hazard ratio (HR)
TheST-elevationmyocardialinfarction(STEMI)andper- depending on the format used in the original publication.
cutaneous coronary intervention (PCI) writing groups to- Alongwithallotherstatisticalpointestimates,theconfidence
getherconsideredthefollowingstudies:Twometa-analyses, interval (CI) for those statistics are added when available.
“A Comparison of Abciximab and Small Molecule Glyco- Consultthefull-textorexecutivesummaryversionsofthe
protein IIb/IIIa Inhibitors in Patients Undergoing Primary ACC/AHA2004GuidelinesfortheManagementofPatients
Percutaneous Coronary Intervention,”6 and “Benefits From With ST-Elevation Myocardial Infarction or the ACC/AHA/
SmallMoleculeAdministrationasComparedWithAbcix- SCAI 2005 Guidelines for Percutaneous Coronary Interven-
imab Among Patients With ST-Segment Elevation Myo- tion, as well as their respective 2007 focused updates, for
cardial Infarction Treated With Primary Angioplasty,”7 policy on clinical areas not covered by the present focused
FINESSE (Facilitated PCI in Patients With ST-Elevation update.2–5Unchangedrecommendationsfrompreviousitera-
MyocardialInfarction),8theHORIZONS-AMI(Harmonizing tions of the guidelines are not listed in this document and
OutcomesWithRevascularizationandStentsinAcuteMyo- remain current policy. Individual recommendations updated
cardial Infarction),9 BRAVE-3 (Bavarian Reperfusion Alter- in this focused update will be incorporated into future
natives Evaluation-3),10 MULTISTRATEGY (Multicentre revisions of the full-text guidelines.
Evaluation of Single High-Dose Bolus Tirofiban Versus
1.2. Organization of Committee and Relationships With
AbciximabWithSirolimus-ElutingStentorBareMetalStent
Industry and Other Entities
in Acute Myocardial Infarction Study),11 ON-TIME 2 (On-
For this focused update, all members of the 2004 STEMI
going Tirofiban in Myocardial Infarction Evaluation),12
guideline,2007STEMIfocusedupdate,2005PCIguideline,
TRITON-TIMI 38 (Trial to Assess Improvement in Thera-
and 2007 PCI focused update writing committees were
peutic Outcomes by Optimizing Platelet Inhibition With
invited to participate; those who agreed (referred to as the
Prasugrel–Thrombolysis in Myocardial Infarction),13
2009 Focused Update Writing Group) were required to
TRANSFER-AMI (Trial of Routine ANgioplasty and Stent-
disclose all relationships with industry and other entities
ing after Fibrinolysis to Enhance Reperfusion in Acute
relevanttothedataunderconsideration.Thepoliciesusedfor
Myocardial Infarction),14 CARESS-in-AMI (Combined Ab-
relationships with industry were those in effect at the initial
ciximab Reteplase Stent Study in Acute Myocardial Infarc-
meeting of this committee, which included disclosure of
tion),15 NICE-SUGAR (Normoglycemia in Intensive Care
relationships12monthspriortoinitiationandachairwithno
Evaluation—Survival Using Glucose Algorithm Regula-
relevant relationships except in a situation where more than
tion),16 TAPAS (Thrombus Aspiration during Percutaneous
onechairisnamed.Inthiscircumstance,onechairwillhave
coronary intervention in Acute myocardial infarction
no relevant relationships and the other may have relation-
Study),17andEXPIRA(ThrombectomyWithExportCatheter
ships. Each recommendation required a confidential vote by
in Infarct-Related Artery During Primary Percutaneous Cor-
the writing group members before and after external review
onary Intervention).18 Additionally, the PCI writing group
ofthedocument.Anywritinggroupmemberwitharelation-
considered the CARE (Cardiac Angiography in Renally
ship with industry relevant to the recommendation was
ImpairedPatients),19FAME(FractionalFlowReserveversus
recused from voting on that recommendation. The PCI
Angiography for Multivessel Evaluation) study,20 SYNTAX
writing group included 2 representatives from SCAI.
(SynergyBetweenPercutaneousInterventionWithTaxusand
Cardiac Surgery),21 Early ACS (Early versus Delayed, Pro- 1.3. Document Review and Approval
visional Eptifibatide in Acute Coronary Syndromes),22 and This document was reviewed by 3 official reviewers nomi-
TIMACS (Timing of Intervention in Patients With Acute natedbytheACCFand4officialreviewersnominatedbythe
Coronary Syndromes) studies.23 When considering the new AHA,1officialreviewernominatedbytheSCAI,6review-
dataforthisfocusedupdate,thewritinggroupfacedthetask ersfromtheACCFInterventionalCouncil,2reviewersfrom
of weighing evidence from studies that had enrolled large the ACCF Imaging Council, and 22 content reviewers. All
numbersofsubjectsoutsideNorthAmerica.Althoughnoting reviewerinformationonrelationshipswithindustryandother
thatpracticepatternsandtherigorappliedtodatacollection, entities was collected and distributed to the writing commit-
aswellasthegeneticmakeupofsubjects,mayinfluencethe tee and is published in Appendix 3. This document was
observedmagnitudeofatreatment’seffect,thewritinggroup approved for publication by the governing bodies of the
believedthedatawererelevanttotheformulationofrecom- ACCF,theAHA,andtheSCAI(specifically,thePCIportion
mendations for management of STEMI and PCI in North of the guideline).
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2276 Circulation December 1, 2009
Table2. RecommendationsfortheUseofGlycoproteinIIb/IIIaReceptorAntagonists
2004/2005/2007Recommendations:2004STEMI
GuidelineSection6.3.1.6.8.2.3;Also2005PCI
GuidelineSection6.2.2 2009JointSTEMI/PCIFocusedUpdateRecommendations Comments
ClassIIa
1. Itisreasonabletostarttreatmentwithabciximab 1. ItisreasonabletostarttreatmentwithglycoproteinIIb/IIIa Modifiedrecommendation
asearlyaspossiblebeforeprimaryPCI(withor receptorantagonists(abciximab9,11(cid:2)LevelofEvidence:A(cid:3), (classof
withoutstenting)inpatientswithSTEMI.(Levelof tirofiban11,12(cid:2)LevelofEvidence:B(cid:3)oreptifibatide6,7,9(cid:2)Levelof recommendation
Evidence:B) Evidence:B(cid:3))atthetimeofprimaryPCI(withorwithoutstenting) changedfromIIbtoIIa
inselectedpatientswithSTEMI. fortirofibanand
eptifibatide).
ClassIIb
1. Treatmentwithtirofibanoreptifibatidemaybe 1. TheusefulnessofglycoproteinIIb/IIIareceptorantagonists(aspart Modifiedrecommendation
consideredbeforeprimaryPCI(withorwithout ofapreparatorypharmacologicalstrategyforpatientswithSTEMI (textmodified;levelof
stenting)inpatientswithSTEMI.(Levelof beforetheirarrivalinthecardiaccatheterizationlaboratoryfor evidencechangedfrom
Evidence:C) angiographyandPCI)isuncertain.8,10(LevelofEvidence:B) CtoB).
STEMI and PCI Focused Update Section receiving high-dose tirofiban (25 mcg/kg bolus followed by
0.15 mcg/kg per min for 18 hours) at first medical contact
2. Recommendations for the Use of Glycoprotein
before transport for primary PCI were also treated with
IIb/IIIa Receptor Antagonists
unfractionatedheparin(UFH;5000U),clopidogrel(600mg),
(See Table 2 and Appendix 4.)
and ASA. Patients in the high-dose tirofiban group had
2.1. Glycoprotein IIb/IIIa Receptor Antagonists improved ST-segment resolution (primary end point) before
In considering the use of intravenous glycoprotein (GP) and1hourafterPCI(P(cid:1)0.003)comparedwiththosereceiv-
IIb/IIIa receptor antagonists for STEMI, the writing group ing placebo (NNT(cid:1)100). However, there was no significant
noted that much of the evidence favoring the use of these difference in Thrombolysis In Myocardial Infarction (TIMI)
agentswasestablishedintheerabeforedualoralantiplatelet grade 3 flow or blush grade and no significant difference in
therapyandlargelybyplacebo-controlledcomparisons.Con- major bleeding or minor bleeding. There was no significant
temporary management of STEMI patients involves a com- difference in death, recurrent MI, or urgent target-vessel
plexarrayofantithrombotics,includingdualoralantiplatelet revascularization (TVR) between the tirofiban and placebo
therapy (aspirin [acetylsalicylic acid; ASA] plus a thienopy- groups at 30 days.25
ridine) and an anticoagulant. There is a paucity of trials In the HORIZONS-AMI trial,9 patients undergoing pri-
adequately powered for assessment of clinical end points that mary PCI for STEMI were randomized to treatment with
have reevaluated the current relative role of intravenous GP UFH plus a GP IIb/IIIa receptor antagonist (abciximab or
IIb/IIIareceptorantagonistswithrespecttootherpharmacolog- double-boluseptifibatide)ortobivalirudinalonewithprovi-
icaltherapyinSTEMIpatients.Accordingly,areevaluationof sional IIb/IIIa. Aspirin and a thienopyridine were adminis-
thevalueofGPIIb/IIIaantagonistsinSTEMIisappropriate,but tered before catheterization. (See the full discussion of the
theabilitytodrawdefinitiveconclusionsislimited. trial under Section 4, Recommendations for the Use of
At least 3 trials evaluated GP IIb/IIIa antagonists as ParenteralAnticoagulants.)Sevenhundredfifty-sevenofthe
adjuncts to oral antiplatelet therapy in the setting of primary 1661 patients who received UFH received a double bolus of
PCI.ThefindingsofthesetrialsquestionwhetherGPIIb/IIIa eptifibatideandinfusion,whereas53of1661inthebivaliru-
antagonists provide significant additional benefit to STEMI din arm received eptifibatide. At 30 days, rates of major
patients who have received dual-antiplatelet therapy before bleedingandtotaladverseeventswerehigheramongpatients
catheterization. In the BRAVE-3 study, 800 patients pres- treated with GP IIb/IIIa antagonists and heparin than among
entingwithin24hoursofaSTEMIwerepretreatedwith600 those given bivalirudin alone.
mg of clopidogrel and then randomly assigned in a double- Two meta-analyses of randomized trials were published
blind manner to receive either abciximab or placebo in the that compared small-molecule GP IIb/IIIa antagonists with
intensive care unit before being sent for PCI.10 The primary abciximab in STEMI patients undergoing primary PCI.6,7 In
end point was infarct size measured by single photon emis- each case, there was no statistically significant difference in
sion computed tomography before hospital discharge. At 30 30-day mortality, reinfarction, or major TIMI bleeding, and
days,thecompositeofdeath,recurrentmyocardialinfarction therewasnosignificantdifferenceindeathorreinfarctionat
(MI),stroke,orurgentrevascularizationoftheinfarct-related 8 months between groups. There was also no statistically
artery was not significantly different in the 2 groups (abcix- significantdifferenceinpostproceduralTIMIflowgrade3or
imab 5%, placebo 3.8%; 95% CI 0.7 to 2.6; P(cid:1)0.4). There ST-segment resolution. On the basis of these studies, the
wasnosignificantdifferenceininfarctsizeormajorbleeding. present writing group judged that the totality of evidence
ON-TIME2wasarandomized,placebo-controlled,multi- indicatesthatthevariousGPIIb/IIIaantagonistsdemonstrate
center European trial that included 491 patients receiving similar effectiveness in the setting of primary PCI.
high-dose tirofiban and 493 receiving placebo within a MULTISTRATEGY was an open-label, multicenter, ran-
median of 76 minutes from onset of symptoms.12 Patients domized European trial with a 2-by-2 factorial design that
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Kushner et al 2009 Focused Updates: STEMI and PCI Guidelines 2277
randomized 745 STEMI patients undergoing primary PCI to 3.1. Thienopyridines
high-dose bolus tirofiban versus abciximab infusion and Since the publication of the last guidelines,4,5 evidence has
sirolimus-eluting stent versus bare-metal stent (BMS).11 The emerged about prasugrel, a thienopyridine that achieves
prespecifiedprimaryendpointsweretheachievementof50% greater inhibition of platelet aggregation than clopidogrel.27
resolution of ST-segment elevation at 90 minutes after PCI, Thepivotaltrialforprasugrel,TRITON-TIMI38,focusedon
powered for noninferiority, and the rate of major adverse patients with ACS who were referred for PCI.
cardiacevents(MACE)at8months,poweredforsuperiority. TRITON-TIMI38randomlyassigned13608patientswith
AllpatientsreceivedASAattheusualdoses,clopidogrel300 moderate- to high-risk ACS, 3534 of whom had STEMI, to
mgorallythen75mgperday,andUFH.Therewasasimilar receive prasugrel (6813 patients received a 60-mg loading
rateofatleast50%ST-segmentresolutionat90minutesafter dose and a 10-mg daily maintenance dose) or clopidogrel
primaryPCIwithabciximabandtirofiban(RR1.020;97.5% (6795 patients received a 300-mg loading dose and a 75-mg
CI 0.958 to 1.086; P(cid:1)0.001 for noninferiority). Rates of daily maintenance dose) for an average follow-up of 14.5
MACE, including all-cause death, clinical reinfarction, or months. Aspirin was prescribed within 24 hours of PCI.
TVR, and hemorrhagic (major and minor bleeding) compli- Clinicalendpointswereassessedat30and90daysandthen
cations were similar. The incidence of severe or moderate every 3 to 15 months.27
thrombocytopenia was more common with abciximab than Prasugrel was associated with a significant 2.2% absolute
with tirofiban (4.0% versus 0.8%, P(cid:1)0.004). reduction and a 19% relative reduction in the primary
In an analysis of the predictors of stent thrombosis after efficacy end point, a composite of the rate of death due to
primary PCI in acute MI presented at the 2009 ACC Scien- cardiovascularcauses(includingarrhythmia,congestiveheart
tific Sessions, titled “Predictors of Stent Thrombosis After failure, shock, and sudden or unwitnessed death), nonfatal
Primary Angioplasty in Acute Myocardial Infarction: The MI, or nonfatal stroke during the follow-up period. The
HORIZONS-AMI Trial,”69 there was no significant differ- primary efficacy end point occurred in 9.9% of patients
ence in the 1-year rate of stent thrombosis with the heparin
receiving prasugrel and 12.1% of patients receiving clopi-
plus GP IIb/IIIa receptor antagonists compared with eptifi-
dogrel (HR for prasugrel versus clopidogrel 0.81; 95% CI
batide and abciximab (3.6% versus 2.8%, P(cid:1)0.93), which 0.73 to 0.90; P(cid:4)0.001). A significant reduction in the
suggests that eptifibatide has the same impact as abciximab
primaryendpointwasseenintheprasugrelgroupbythefirst
on stent thrombosis incidence.
prespecified time point, which was 3 days (4.7% in the
Oneinvestigation,FINESSE,addressedtheissueoftiming
prasugrel group versus 5.6% in the clopidogrel group; HR
of GP IIb/IIIa antagonist administration. This double-blind, 0.82;95%CI0.71to0.96;P(cid:1)0.01),andpersistedthroughout
randomized, placebo-controlled study of 2453 patients with
thefollow-upperiod.FromDay3totheendofthestudy,the
STEMI explored the use of pre-PCI treatment with a half-
primaryendpointhadoccurredin5.6%ofpatientsreceiving
dose fibrinolytic agent plus abciximab, pre-PCI abciximab
prasugrel and in 6.9% of patients receiving clopidogrel (HR
alone, and abciximab at the time of PCI.8 The primary end 0.80; 95% CI 0.70 to 0.93; P(cid:1)0.003). Prasugrel decreased
pointwasthecompositeofdeathduetoallcauses,ventricular
cardiovascular death, MI, and stroke by 138 events
fibrillation that occurred more than 48 hours after random-
(NNT(cid:1)46).27 The rate of MI with subsequent death due to
ization, cardiogenic shock, and congestive heart failure dur-
cardiovascularcauseswasalsoreducedintheprasugrelgroup
ing the first 90 days after randomization. The results of the
(P(cid:1)0.02). The difference in the primary end point was
trialarediscussedinSection5.1,TriageandTransferforPCI.
largelyrelatedtothedifferenceinratesofnonfatalMI(7.3%
This trial showed no benefit (and a tendency toward excess
for prasugrel versus 9.5% for clopidogrel; HR 0.76; 95% CI
bleeding) with prehospital abciximab compared with abcix-
0.67to0.85;P(cid:4)0.001).Therewerenosignificantdifferences
imab at the time of PCI. The writing group concluded there
inthe2treatmentgroupsintheratesofstrokeorofdeathdue
wasnobenefitofadministrationofabciximabbeforeprimary
tocardiovascularcausesnotprecededbyrecurrentMI(at15
PCI, alone or in combination with reteplase. On the basis of
months,thenonfatalstrokeratewas1.0%forbothprasugrel
this trial and ON-TIME 2, the writing group concluded that
and clopidogrel; HR for prasugrel(cid:1)1.02; CI 0.71 to 1.45;
the use of GP IIb/IIIa antagonists before primary PCI is of
P(cid:1)0.93; the rate of deaths due to cardiovascular causes not
uncertain benefit.
precededbyrecurrentMIwas2.1%forprasugrelversus2.4%
Given the results of the studies cited above, the writing
for clopidogrel; HR 0.89; CI 0.70 to 1.12; P(cid:1)0.31). There
group concluded that in the setting of dual-antiplatelet ther-
weresignificantreductionsintheratesofischemiceventsin
apy with UFH or bivalirudin as the anticoagulant, current
the prasugrel group compared with the clopidogrel group:
evidence indicates that adjunctive use of a GP IIb/IIIa
Rates of MI were 7.4% for prasugrel versus 9.7% for
antagonistcanbeusefulatthetimeofprimaryPCIbutcannot
be recommended as routine therapy. These agents might clopidogrel (P(cid:4)0.001); urgent TVR rates were 2.5% for
provide more benefit in selective use, for example, for the prasugrel versus 3.7% for clopidogrel (P(cid:4)0.001); and rates
patientwithalargethrombusburdenorforpatientswhohave ofstentthrombosiswere1.1%forprasugrelversus2.4%for
not received adequate thienopyridine loading. clopidogrel (HR 0.48; 95% CI 0.36 to 0.64; P(cid:4)0.001).
Prasugrelwasassociatedwithasignificantincreaseinthe
3. Recommendations for the Use of rateofbleeding,notably,TIMImajorhemorrhage,whichwas
Thienopyridines observedin2.4%ofpatientstakingprasugrelandin1.8%of
(See Table 3 and Appendix 4.) patientstakingclopidogrel(HRforprasugrelversusclopidogrel
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2278 Circulation December 1, 2009
Table3. RecommendationsfortheUseofThienopyridines
Comments(AllModified
RecommendationsArefor
STEMIRecommendations PCIRecommendations 2009JointSTEMI/PCIFocusedUpdateRecommendations PatientsWithACS)
ClassI
2004STEMIGuidelines, 2007PCIUpdate,Table14
Section7.4.4
4. Forpatientswhohaveundergone 4. Aloadingdoseofclopidogrel,*generally 1. AloadingdoseofthienopyridineisrecommendedforSTEMIpatientsfor Modifiedrecommendation
diagnosticcardiaccatheterization 600mg,shouldbeadministeredbefore whomPCIisplanned.Regimensshouldbe1ofthefollowing: (changedtext).
andforwhomPCIisplanned, orwhenPCIisperformed.(Levelof a. Atleast300to600mgofclopidogrel†shouldbegivenasearlyas
clopidogrelshouldbestartedand Evidence:C)InpatientsundergoingPCI possiblebeforeoratthetimeofprimaryornonprimaryPCI.(Levelof
continuedforatleast1month within12to24hoursofreceiving Evidence:C)
afterbaremetalstent fibrinolytictherapy,aclopidogreloral b. Prasugrel60mgshouldbegivenassoonaspossibleforprimary
implantationandforseveral loadingdoseof300mgmaybe PCI.26,27(LevelofEvidence:B)
monthsafterdrug-elutingstent considered.(LevelofEvidence:C) c. ForSTEMIpatientsundergoingnonprimaryPCI,thefollowing
implantation(3monthsfor regimensarerecommended:
sirolimus,6monthsfor (i) Ifthepatienthasreceivedfibrinolytictherapyandhasbeengiven
paclitaxel)andforupto12 clopidogrel,clopidogrelshouldbecontinuedasthethienopyridine
monthsinpatientswhoarenot ofchoice(LevelofEvidence:C);
athighriskforbleeding.(Level (ii) Ifthepatienthasreceivedfibrinolytictherapywithouta
ofEvidence:B) thienopyridine,aloadingdoseof300to600mg‡ofclopidogrel
shouldbegivenasthethienopyridineofchoice(Levelof
Evidence:C);
(iii) Ifthepatientdidnotreceivefibrinolytictherapy,eitheraloading
doseof300to600mgofclopidogrelshouldbegivenor,once
thecoronaryanatomyisknownandPCIisplanned,aloading
doseof60mgofprasugrelshouldbegivenpromptlyandno
laterthan1hourafterthePCI.26,27(LevelofEvidence:B)
5. Forallpost-PCIstentedpatientsreceiving 2. Thedurationofthienopyridinetherapyshouldbeasfollows: Modifiedrecommendation
aDES,clopidogrel75mgdailyshouldbe a. Inpatientsreceivingastent(BMSordrug-elutingstent[DES])during (pertainstoSTEMIand
givenforatleast12monthsifpatients PCIforACS,clopidogrel75mgdaily†27–29(LevelofEvidence:B)or unstableangina
arenotathighriskofbleeding.For prasugrel10mgdaily§27(LevelofEvidence:B)shouldbegivenfor (cid:2)UA(cid:3)/non-STEMI
post-PCIpatientsreceivingaBMS, atleast12months; (cid:2)NSTEMI(cid:3)basedon
clopidogrelshouldbegivenfora b. Iftheriskofmorbiditybecauseofbleedingoutweighstheanticipated TRITON-TIMI38).
minimumof1monthandideallyupto benefitaffordedbythienopyridinetherapy,earlierdiscontinuation
12months(unlessthepatientisat shouldbeconsidered.(LevelofEvidence:C)
increasedriskofbleeding;thenitshould
begivenforaminimumof2weeks).
(LevelofEvidence:B)
2007STEMIUpdate,Section9
2. Inpatientstakingclopidogrelin 3. InpatientstakingathienopyridineinwhomCABGisplannedandcan Modifiedrecommendation
whomCABGisplanned,thedrug bedelayed,itisrecommendedthatthedrugbediscontinuedtoallow (addedprasugrel).
shouldbewithheldforatleast5 fordissipationoftheantiplateleteffect.(LevelofEvidence:C)The
daysandpreferablyfor7days periodofwithdrawalshouldbeatleast5daysinpatientsreceiving
unlesstheurgencyfor clopidogrel2,30(LevelofEvidence:B)andatleast7daysinpatients
revascularizationoutweighsthe receivingprasugrel†27(LevelofEvidence:C),unlesstheneedfor
risksofexcessbleeding.(Level revascularizationand/orthenetbenefitofthethienopyridineoutweighs
ofEvidence:B) thepotentialrisksofexcessbleeding.31(LevelofEvidence:C)
ClassIIa
2004STEMIGuidelines,Section 2007PCIUpdate,Table14
7.4.4 1. Ifclopidogrelisgivenatthetimeof Deletedrecommendation
procedure,supplementationwithGP
IIb/IIIareceptorantagonistscanbe
beneficial.(LevelofEvidence:B)
2. Forpatientswithanabsolute Deletedrecommendation
contraindicationtoaspirin,itis
reasonabletogivea300-mgto600-mg
loadingdoseofclopidogrel,administered
atleast6hoursbeforePCI,and/orGP
IIb/IIIaantagonists,administeredatthe
timeofPCI.(LevelofEvidence:C)
ClassIIb
2004STEMIGuidelines,Section 2007PCIUpdate,Table14
7.4.4 1. Continuationofclopidogreltherapy 1. Continuationofclopidogrelorprasugrel§beyond15monthsmaybe Modifiedrecommendation
beyond1yearmaybeconsideredin consideredinpatientsundergoingDESplacement.27(LevelofEvidence:C) (changedtext).
patientsundergoingDESplacement.
(LevelofEvidence:C)
(Continued)
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Kushner et al 2009 Focused Updates: STEMI and PCI Guidelines 2279
Table3. Continued
Comments(AllModified
RecommendationsArefor
STEMIRecommendations PCIRecommendations 2009JointSTEMI/PCIFocusedUpdateRecommendations PatientsWithACS)
ClassIII
1. InSTEMIpatientswithapriorhistoryofstrokeandtransientischemic Newrecommendation
attackforwhomprimaryPCIisplanned,prasugrelisnotrecommended
aspartofadual-antiplatelettherapyregimen.(LevelofEvidence:C)
*AvailabledataforprasugreluseareforPCIforacutecoronarysyndrome(ACS)andnotelectivePCI.RecommendationsforelectivePCIwithclopidogreluseare
notbeingupdatedinthisguidelinefocusedupdate.
†Theoptimumloadingdoseofclopidogrelhasnotbeenestablished.Randomizedtrialsestablishingitsefficacyandprovidingdataonbleedingrisksusedaloading
doseof300mgorallyfollowedbyadailyoraldoseof75mg.26,27Higheroralloadingdosessuchas600mgormorethan900mg36ofclopidogrelmorerapidlyinhibit
plateletaggregationandachieveahigherabsolutelevelofinhibitionofplateletaggregation,buttheadditiveclinicalefficacyandsafetyofhigheroralloadingdoses
havenotbeenrigorouslyestablished.ThenecessityforgivingaloadingdoseofclopidogrelbeforePCIisdrivenbythepharmacokineticsofclopidogrel,forwhich
severalhoursarerequiredtoachievedesiredlevelsofplateletinhibition.Forpost-PCIpatientsreceivingastent(BMSorDES),adailymaintenancedoseshouldbe
givenforatleast12monthsandforupto15monthsunlesstheriskofbleedingoutweighstheanticipatednetbenefitaffordedbyathienopyridine.
‡Clopidogrelloadingdoseafterfibrinolytictherapy:Forpatientsgivenfibrin-andnon–fibrin-specificfibrinolyticdrugswhoareundergoingPCIwithin24hours,300
mg; for patients given a fibrin-specific fibrinolytic undergoing PCI after more than 24 hours, 300 to 600 mg; for patients given a non–fibrin-specific fibrinolytic
undergoingPCIbetween24and48hours,300mg;forpatientsgivenanon–fibrin-specificfibrinolyticundergoingPCIafter48hours,300to600mg.
§Patientsweighing(cid:4)60kghaveanincreasedexposuretotheactivemetaboliteofprasugrelandanincreasedriskofbleedingona10-mgonce-dailymaintenance
dose.Considerationshouldbegiventoloweringthemaintenancedoseto5mginpatientswhoweigh(cid:4)60kg.Theeffectivenessandsafetyofthe5-mgdosehave
notbeenstudiedprospectively.Forpost-PCIpatientsreceivingastent(BMSorDES),adailymaintenancedoseshouldbegivenforatleast12monthsandforup
to15monthsunlesstheriskofbleedingoutweighstheanticipatednetbenefitaffordedbyathienopyridine.Donotuseprasugrelinpatientswithactivepathological
bleedingorahistoryoftransientischemicattackorstroke.Inpatients(cid:1)75yearsofage,prasugrelisgenerallynotrecommendedbecauseoftheincreasedriskof
fatalandintracranialbleedinganduncertainbenefit,exceptinhigh-risksituations(patientswithdiabetesorahistoryofpriorMI)inwhichitseffectappearstobe
greateranditsusemaybeconsidered.DonotstartprasugrelinpatientslikelytoundergourgentCABG.Whenpossible,discontinueprasugrelatleast7daysbefore
anysurgery.Additionalriskfactorsforbleedingincludebodyweight(cid:4)60kg,propensitytobleed,andconcomitantuseofmedicationsthatincreasetheriskofbleeding
(eg,warfarin,heparin,fibrinolytictherapy,orchronicuseofnonsteroidalanti-inflammatorydrugs).
1.32; 95% CI 1.03 to 1.68, P(cid:1)0.03), which represented an A post hoc analysis suggested there were 3 subgroups of
increaseintherelativerateofmajorbleedingof32%.Fromthe ACSpatientswhodidnothaveafavorablenetclinicalbenefit
standpoint of safety, prasugrel was associated with an in- (defined as the rate of death due to any cause, nonfatal MI,
crease of 35 TIMI major and non–coronary artery bypass nonfatal stroke, or non–CABG-related nonfatal TIMI major
graft bleeds (number needed to harm(cid:1)167).27 Also, greater bleeding) from the use of prasugrel or who had net harm:
ratesoflife-threateningbleedingwereevidentintheprasug- Patients with a history of stroke or transient ischemic attack
rel group than in the clopidogrel group: 1.4% versus 0.9%, (TIA) before enrollment had net harm from prasugrel (HR
respectively (HR for prasugrel 1.52; 95% CI 1.08 to 2.13; 1.54;95%CI1.02to2.32;P(cid:1)0.04),patients75yearsofage
P(cid:1)0.01), which included nonfatal bleeding (1.1% versus andolderhadnonetbenefitfromprasugrel(HR0.99;95%CI
0.9%; HR for prasugrel 1.25; 95% CI 0.87 to 1.81; 0.81to1.21;P(cid:1)0.92);andpatientswithabodyweightofless
P(cid:1)0.23) and fatal bleeding (0.4% versus 0.1%; HR for than60kghadnonetbenefitfromprasugrel(HR1.03;95%
prasugrel 4.19; 95% CI 1.58 to 11.11; P(cid:1)0.002). In the CI0.69to1.53;P(cid:1)0.89).Inbothtreatmentgroups,patients
few patients who underwent coronary artery bypass graft with at least 1 of these risk factors had higher rates of
(CABG),TIMImajorbleedingthrough15monthswasalso bleedingthanthosewithoutthem.27Apharmacokineticanal-
greaterwithprasugrelthanwithclopidogrel(13.4%versus ysis showed greater exposure to the active metabolite of
3.2%,respectively;HRforprasugrel4.73;95%CI1.90to prasugrelforpatientswhoweighedlessthan60kgandwho
11.82; P(cid:4)0.001).27 Despite the increase in bleeding, the were 75 years old or older.38
net clinical-benefit end point, which included all-cause The US Food and Drug Administration (FDA) approved
mortality, ischemic events, and major bleeding events, prasugrel in July 2009 and incorporated the aforementioned
favored prasugrel.27 subgroup findings into its labeling by citing a contraindica-
Prasugrel showed superior efficacy in major prespecified tionagainstprasugreluseinpatientswithahistoryofTIAor
subgroupsintheoverallACSpopulation.Thebenefittendedto stroke and active pathological bleeding. The FDA further
be greater among the 3146 patients with diabetes (12.2% of recommends that consideration be given to lowering the
whomhadtheprimaryendpointintheprasugrelgroupversus maintenancedoseofprasugrelto5mginpatientswhoweigh
17.0%intheclopidogrelgroup;HR0.70;95%CI0.58to0.85; lessthan60kg,withanotethattheeffectivenessandsafety
P(cid:4)0.001) than among the 10462 patients without diabetes ofthe5-mgdosehavenotbeenstudiedprospectivelytodate.
(9.2%ofwhomhadtheprimaryendpointintheprasugrelgroup The FDA labeling information includes a general warning
versus10.6%intheclopidogrelgroup;HR0.86;95%CI0.76to againsttheuseofprasugrelinpatientsolderthan75yearsof
0.98;P(cid:1)0.02).Therateofdefiniteorprobablestentthrombosis age because of concerns of an increased risk of fatal and
wassignificantlyreducedintheprasugrelgroupcomparedwith intracranial bleeding and uncertain benefit, except in high-
theclopidogrelgroup,asnoted.27 risk situations (patients with diabetes or a history of prior
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