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 Copyright © 2009 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/120/22/2271 An erratum has been published regarding this article. Please see the attached page for: http://circ.ahajournals.org/content/121/12/e257.full.pdf Data Supplement (unedited) at: http://circ.ahajournals.org/content/suppl/2010/02/01/CIRCULATIONAHA.109.192663.DC1.html Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published inCirculation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in thePermissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/ Downloaded from http://circ.ahajournals.org/ by guest on October 24, 2012 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 Downloaded from http://circ.ahajou2r2na7l1s.org/ by guest on October 24, 2012 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 Downloaded from http://circ.ahajournals.org/ by guest on October 24, 2012 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 Downloaded from http://circ.ahajournals.org/ by guest on October 24, 2012 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- Downloaded from http://circ.ahajournals.org/ by guest on October 24, 2012 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). Downloaded from http://circ.ahajournals.org/ by guest on October 24, 2012 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 Downloaded from http://circ.ahajournals.org/ by guest on October 24, 2012 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 Downloaded from http://circ.ahajournals.org/ by guest on October 24, 2012 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) Downloaded from http://circ.ahajournals.org/ by guest on October 24, 2012 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 Downloaded from http://circ.ahajournals.org/ by guest on October 24, 2012