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  2017ESCfocusedupdateondualantiplatelettherapyincoronaryarterydiseasedevelopedincollaborationwithEACTS The Task Force for dual antiplatelet therapy in coronary arterydisease of the European Society of Cardiology (ESC) and of theEuropean Association for Cardio-Thoracic Surgery (EACTS) Authors/Task Force Members: Marco Valgimigli* (Chairperson) (Switzerland),He´ctor Bueno (Spain), Robert A. Byrne (Germany), Jean-Philippe Collet (France),Francesco Costa (Italy), Anders Jeppsson 1 (Sweden), Peter Ju¨ni (Canada),Adnan Kastrati (Germany), Philippe Kolh (Belgium), Laura Mauri (USA),Gilles Montalescot (France), Franz-Josef Neumann (Germany),Mate Petricevic 1 (Croatia), Marco Roffi (Switzerland), Philippe Gabriel Steg(France), Stephan Windecker (Switzerland), and Jose Luis Zamorano (Spain) Additional Contributor: Glenn N. Levine (USA)Document Reviewers: Lina Badimon (CPG Review Coordinator) (Spain), Pascal Vranckx (CPG ReviewCoordinator) (Belgium), Stefan Agewall (Norway), Felicita Andreotti (Italy), Elliott Antman (USA),Emanuele Barbato (Italy), Jean-Pierre Bassand (France), Raffaele Bugiardini (Italy), Mustafa Cikirikcioglu 1 (Switzerland), Thomas Cuisset (France), Michele De Bonis (Italy), Victora Delgado (The Netherlands),Donna Fitzsimons (UK), Oliver Gaemperli (Switzerland), Nazzareno Galie` (Italy), Martine Gilard (France), * Corresponding author: Marco Valgimigli, Cardiology, Inselspital, Freiburgstrasse 8, 3010 Bern, Switzerland. Tel: þ 41316323077, Fax: þ 41107035258, E-mail: marco.valgimigli@insel.ch. ESC Committee for Practice Guidelines (CPG) and National Cardiac Societies document reviewers: listed in the Appendix. 1 Representing the EACTSESC entities having participated in the development of this document:Associations : Acute Cardiovascular Care Association (ACCA), European Association of Preventive Cardiology (EAPC), European Association of Percutaneous Cardiovascular Interventions (EAPCI). Working Groups : Cardiovascular Pharmacotherapy, Cardiovascular Surgery, Coronary Pathophysiology and Microcirculation, Peripheral Circulation, Pulmonary Circulation andRight Ventricular Function, Thrombosis, Valvular Heart Disease.The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESCGuidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to OxfordUniversity Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC ( journals.permissions@oxfordjournals.org). Disclaimer  . The ESC Guidelines represent the views of the ESC and were produced after careful consideration of the scientific and medical knowledge and the evidence availableat the time of their publication. The ESC is not responsible in the event of any contradiction, discrepancy and/or ambiguity between the ESC Guidelines and any other official recom-mendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encour-aged to take the ESC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or  therapeutic medical strategies; however, the ESC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate andaccurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the ESC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competentpublic health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also thehealth professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.The article has been co-published with permission in the European Heart Journal [DOI: 10.1093/eurheartj/ehx419] on behalf of the European Society of Cardiology andEuropean Journal of Cardio-Thoracic Surgery [DOI 10.1093/ejcts/ezx334] on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved in respectof European Heart Journal, V C European Society of Cardiology 2017. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’sstyle. Either citation can be used when citing this article.For permissions, please email journals.permissions@oup.com. European Heart Journal (2018)  39 , 213–254  ESC GUIDELINES doi:10.1093/eurheartj/ehx419 D ownl   o a d  e d f  r  om h  t   t   p s :  /   /   a c  a d  emi   c . o u p. c  om /   e ur h  e ar  t   j   /   ar  t  i   c l   e- a b  s  t  r  a c  t   /   3  9  /   3  /  2 1  3  /  4  0  9  5  0 4  3  b  y  g u e s  t   on1 4 A  u g u s  t  2  0 1  9   .................................................................................................. Christian W. Hamm (Germany), Borja Ibanez (Spain), Bernard Iung (France), Stefan James (Sweden), Juhani Knuuti (Finland), Ulf Landmesser (Germany), Christophe Leclercq (France), Maddalena Lettino(Italy), Gregory Lip (UK), Massimo Francesco Piepoli (Italy), Luc Pierard (Belgium),Markus Schwerzmann (Switzerland), Udo Sechtem (Germany), Iain A. Simpson (UK), Miguel Sousa Uva  1 (Portugal), Eugenio Stabile (Italy), Robert F. Storey (UK), Michal Tendera (Poland), Frans Van de Werf (Belgium), Freek Verheugt (The Netherlands), and Victor Aboyans (CPG Supervisor) (France)The disclosure forms of all experts involved in the development of this focused update are available onthe ESC website http://www.escardio.org/guidelines.The Addendaand ClinicalCasescompanion documentofthisfocused updateareavailable at:www.escardio.org/Guidelines/Clinical-Practice-Guidelines/2017-focused-update-on-dual-antiplatelet-therapy-dapt Web addenda Online publish-ahead-of-print 26 August 2017 ................................................................................................................................................................................................... Keywords  Guidelines  ã  Aspirin  ã  Clopidogrel  ã  Ticagrelor   ã  Prasugrel  ã  Dual antiplatelet therapy  ã  Acute coronarysyndromes  ã  Coronary artery bypass grafting  ã  Coronary artery disease  ã  Drug-eluting stents  ã  Myocardialinfarction  ã  Stent thrombosis  ã  Bleeding  ã  Percutaneous coronary intervention  ã  Recommendation ã  Revascularization  ã  Risk stratification  ã  Stents  ã  Stable angina  ã  Stable coronary artery disease  ã  Oralanticoagulant  ã  Triple therapy  ã  DAPT score  ã  PRECISE-DAPT score  ã  Non-cardiac surgery Table of Contents Abbreviationsandacronyms.. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2151.Preamble... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2162.Introduction.. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2182.1 Short-andlong-termoutcomesafterpercutaneouscoronaryintervention.. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2192.2 Riskofstentthrombosisin relation tostenttype. .. ... ... .. ... .2192.3 Short-andlong-termoutcomesaftercoronaryarterybypasssurgery.. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2192.4 Short-andlong-termoutcomesaftermedicallymanagedacutecoronarysyndrome. .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2193.Efficacy andsafety ofdual antiplatelettherapy andrisk stratificationtools.. ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2193.1 Dualantiplatelettherapyforthepreventionofstent thrombosis. .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2193.2 Dualantiplatelettherapyforthepreventionofspontaneousmyocardialinfarction.. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2193.3 Dualantiplatelettherapyandmortality rate. .. ... .. ... ... .. ... .2193.4Safetyofdualantiplatelettherapy .. .. ... ... .. ... .. ... ... .. ... .2193.5 Riskstratificationtoolsforischaemiaandbleedingrisks .. .. ... .2193.6 TypeofP2Y 12 inhibitorandtimingofinitiation... .. ... ... .. ... .2213.7 Measuresto minimize bleedingwhileondualantiplatelettherapy . .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2233.8 SwitchingbetweenoralP2Y 12 inhibitors. ... .. ... .. ... ... .. ... .2254.Dualantiplatelettherapyandpercutaneouscoronaryintervention... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2264.1 Dualantiplatelettherapyafterpercutaneouscoronaryinterventionforstablecoronaryarterydisease. .. ... .. ... ... .. ... .2264.2 Dualantiplatelettherapyafterpercutaneouscoronaryinterventionforacute coronarysyndrome.. ... .. ... .. ... ... .. ... .2314.3Gapsintheevidence . .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .2335.Dual antiplatelettherapy andcardiacsurgery. ... .. ... ... .. ... .. ...2345.1Dual antiplatelettherapyin patientstreatedwith coronaryartery bypasssurgery forstablecoronaryarterydisease . .. ... .. ...2345.2Dual antiplatelettherapyin patientstreatedwith coronaryartery bypasssurgery foracute coronarysyndrome .. ... .. ... .. ...2345.3Dual antiplatelettherapyforprevention of graftocclusion. .. ...2375.4Gapsinthe evidence .. ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...2376.Dual antiplatelettherapy forpatientswith medicallymanagedacutecoronarysyndrome ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...2377.Dual antiplatelettherapy forpatientswith indicationfororalanticoagulation. ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...2387.1Risk stratificationandstrategiestoimproveoutcomeafter percutaneouscoronaryintervention. ... ... .. ... .. ... ... .. ... .. ...2387.2Durationoftripletherapy .. ... .. ... ... .. ... .. ... ... .. ... .. ...2397.3Cessationofallantiplateletagents... ... .. ... .. ... ... .. ... .. ...2427.4Typeofanticoagulants. ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...2427.5Typeofstent.. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...2428.Electivenon-cardiac surgeryin patientsondualantiplatelet therapy... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...2429.Genderconsiderationandspecialpopulations... .. ... ... .. ... .. ...2459.1Genderspecificities ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...2459.2Diabetesmellitus. .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...2459.3Lower-extremitiesarterydisease ... ... .. ... .. ... ... .. ... .. ...2459.4Complexpercutaneouscoronaryintervention ... ... .. ... .. ...2489.5Dual antiplatelettherapydecision makingin patientswithstentthrombosis . ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...2489.6Patientswho developbleedingwhileontreatment... .. ... .. ...24810.Keymessages.. .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...24911.Evidenced-based‘todo andnotto do’messages . ... ... .. ... .. ...24912.WebaddendaandClinicalCasescompaniondocument .. ... .. ...25113.Appendix .. ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...25114.References . ... .. ... .. ... ... .. ... .. ... ... .. ... .. ... ... .. ... .. ...252 214  ESC Guidelines D ownl   o a d  e d f  r  om h  t   t   p s :  /   /   a c  a d  emi   c . o u p. c  om /   e ur h  e ar  t   j   /   ar  t  i   c l   e- a b  s  t  r  a c  t   /   3  9  /   3  /  2 1  3  /  4  0  9  5  0 4  3  b  y  g u e s  t   on1 4 A  u g u s  t  2  0 1  9   ............................................................................................................................................................................ Abbreviations and acronyms ABC Age, Biomarkers (GDF-15, cTnT-hs, andhaemoglobin), and Clinical history(previous bleeding)ACCA Acute Cardiovascular Care AssociationACCOAST A Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention Or as Pretreatment At the Time of Diagnosisin Patients with Non-ST-ElevationMyocardial InfarctionACS Acute coronary syndromeADP Adenosine 5’-diphosphateAF Atrial fibrillationANTARCTIC Platelet Function Monitoring to AdjustAntiplatelet Therapy in Elderly PatientsStented for an Acute Coronary SyndromeARCTIC-Interruption Assessment by a Double Randomisation of aConventional Antiplatelet Strategy Versus aMonitoring-Guided Strategy for Drug-Eluting Stent Implantation and, of TreatmentInterruption Versus Continuation 1Year After Stenting-InterruptionART Arterial Revascularisation TrialASA Acetylsalicylic acidATACAS Aspirin and Tranexamic Acid for Coronary Artery SurgeryATLANTIC Administration of Ticagrelor in the CathLab or in the Ambulance for New STElevation Myocardial Infarction to Open the Coronary ArteryBARC Bleeding Academic Research Consortium b.i.d Bis in die  (twice a day)BMS Bare-metal stentCABG Coronary artery bypass graft surgeryCAD Coronary artery diseaseCHADS 2  Cardiac failure, Hypertension, Age,Diabetes, Stroke (Doubled)CHA 2 DS 2 -VASc Cardiac failure, Hypertension, Age >_ 75 (2points), Diabetes, Stroke (2 points)  –  Vascular disease, Age 65  –  74, Sex categoryCHARISMA Clopidogrel for High AtherothromboticRisk and Ischemic Stabilization,Management, and AvoidanceCI Confidence intervalCOGENT Clopidogrel and the Optimization of Gastrointestinal Events TrialCORONARY CABG Off or On Pump RevascularizationStudyCPG Committee for Practice GuidelinesCrCl Creatinine clearanceCREDO Clopidogrel for the Reduction of EventsDuring ObservationCRUSADE Can Rapid risk stratification of Unstableangina patients Suppress ADverseoutcomes with Early implementation of  the ACC/AHA GuidelinesCURE Clopidogrel in Unstable Angina to PreventRecurrent EventsCYP Cytochrome P450DAPT Dual antiplatelet therapyDES Drug-eluting stentEACTS European Association for Cardio-ThoracicSurgeryEAPC European Association of PreventiveCardiologyEAPCI European Association of PercutaneousCardiovascular InterventionsESC European Society of CardiologyEXAMINATION Clinical Evaluation of the Xience-V stentin Acute Myocardial INfArcTIONEXCELLENT Efficacy of Xience/Promus Versus Cypher  to Reduce Late Loss After StentingFDA Food and Drug AdministrationGUSTO Global Use of Strategies to OpenOccluded Coronary ArteriesHAS-BLED Hypertension, Abnormal renal and liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly(> 65years), Drugs and alcoholHR Hazard ratioI-LOVE-IT 2 Evaluate Safety and Effectiveness of theTivoli DES and the Firebird DES for Treatment of Coronary RevascularizationINR International normalized ratioISAR Intracoronary Stenting andAntithrombotic RegimenISAR-SAFE Intracoronary Stenting andAntithrombotic Regimen: Safety andEfficacy of 6Months Dual AntiplateletTherapy After Drug-Eluting StentingISAR-TRIPLE Intracoronary Stenting andAntithrombotic Regimen  –  Testing of a 6- Week Versus a 6-Month ClopidogrelTreatment Regimen in Patients WithConcomitant Aspirin and OralAnticoagulant Therapy Following Drug-Eluting StentingITALIC Is There a Life for DES After Discontinuation of ClopidogrelIVUS XPL Impact of Intravascular UltrasoundGuidance on Outcomes of XIENCEPRIME Stents in Long LesionsLATE Late coronary Arterial Thrombotic EventsLEAD Lower-extremities artery diseaseLEADERS-FREE Prospective randomized comparison of  the BioFreedom biolimus A9 drug-coatedstent versus the gazelle bare-metal stentin patients at high bleeding risk LVEF Left ventricular ejection fractionMACCE Major adverse cardiac andcerebrovascular eventsMACE Major adverse cardiovascular events ESC Guidelines  215 D ownl   o a d  e d f  r  om h  t   t   p s :  /   /   a c  a d  emi   c . o u p. c  om /   e ur h  e ar  t   j   /   ar  t  i   c l   e- a b  s  t  r  a c  t   /   3  9  /   3  /  2 1  3  /  4  0  9  5  0 4  3  b  y  g u e s  t   on1 4 A  u g u s  t  2  0 1  9   .......................................................................................................................................................................... MATRIX Minimizing Adverse Haemorrhagic Eventsby TRansradial Access Site and SystemicImplementation of angioXMI Myocardial infarctionNACE Net adverse clinical eventsNCDR National Cardiovascular Data RegistryNNT Number needed to treatNOAC Non-vitamin K oral anticoagulantNORSTENT NORwegian coronary STENT trialNSTE-ACS Non-ST elevation acute coronary syndromeNSTEMI Non-ST-segment elevation myocardialinfarctionOAC Oral anticoagulant o.d. Omni die  (once a day)OPTIMIZE Optimized Duration of ClopidogrelTherapy Following Treatment With theZotarolimus-Eluting Stent in Real-WorldClinical PracticeOR Odds ratioPARIS Patterns of Nonadherence to AntiplateletRegimens in Stented PatientsPCI Percutaneous coronary interventionPEGASUS-TIMI 54 Prevention of Cardiovascular Events inPatients with Prior Heart Attack UsingTicagrelor Compared to Placebo on aBackground of Aspirin  –  Thrombolysis inMyocardial Infarction 54PIONEER AF-PCI Rivaroxaban and a dose- adjusted oralvitamin K antagonist treatment strategy insubjects with atrial fibrillation whoundergo percutaneous coronaryinterventionPLATO PLATelet inhibition and patient OutcomesPPI Proton pump inhibitor PRECISE-DAPT PREdicting bleeding Complications Inpatients undergoing Stent implantationand subsEquent Dual Anti PlateletTherapyPRODIGY PROlonging Dual antiplatelet treatmentafter Grading stent-induced intimalhYperplasia studyPROTECT Patient-Related Outcomes With Endeavor vs Cypher Stenting q.d. Quaque die  (one a day)RCT Randomized controlled trialREDUAL-PCI Evaluation of Dual Therapy WithDabigatran vs. Triple Therapy With Warfarin in Patients With AFib ThatUndergo a PCI With StentingRESET Real Safety and Efficacy of 3-Month DualAntiplatelet Therapy Following Endeavor Zotarolimus-Eluting Stent ImplantationROOBY Veterans Affairs Randomized On/Off Bypass trialRR Relative risk RRR Relative risk reductionSECURITY Second Generation Drug-Eluting StentImplantation Followed by Six- VersusTwelve-Month Dual Antiplatelet TherapySTEMI ST-segment elevation myocardialinfarctionSTREAM STrategic Reperfusion Early After Myocardial InfarctionSYNTAX Synergy Between Percutaneous CoronaryIntervention With Taxus and CardiacSurgeryTIA Transient ischaemic attack TIMI Thrombolysis In Myocardial InfarctionTL-PAS Taxus Liberte´ Post Approval StudyTRA 2  P-TIMI 50 Thrombin Receptor Antagonist inSecondary Prevention of Atherothrombotic Ischemic EventsTRACER Thrombin Receptor Antagonist for Clinical Event Reduction in AcuteCoronary SyndromeTRILOGY ACS Targeted Platelet Inhibition to Clarify theOptimal Strategy to Medically ManageAcute Coronary SyndromesTRITON-TIMI 38 Trial to Assess Improvement in TherapeuticOutcomes by Optimizing Platelet Inhibitionwith Prasugrel  –  Thrombolysis in MyocardialInfarctionTROPICAL-ACS Testing Responsiveness to PlateletInhibition on Chronic AntiplateletTreatment For Acute CoronarySyndromes TrialVA Veterans’ AdministrationVKA Vitamin K antagonist WOEST What is the Optimal antiplatElet andanticoagulant therapy in patients withOAC and coronary StenTingZES Zotarolimus-eluting stentZEUS Zotarolimus-eluting Endeavor sprint stentin Uncertain DES Candidates24/7 24h a day, seven days a week  1. Preamble Guidelines and Focused Updates written under the auspices of theEuropean Society of Cardiology’s (ESC) Committee for PracticeGuidelines (CPG) summarize and evaluate available evidence with the aim of assisting health professionals in selecting the best manage-ment strategies for an individual patient with a given condition. TheCPG Guidelines’ and Focused Updates’ recommendations shouldfacilitatedecisionmakingofhealthprofessionalsintheirdailypractice.However, the final decisions concerning an individual patient must bemade by the responsible health professional(s) in consultation with the patientand caregiverasappropriate.A great number of guidelines and focused updates have beenissued in recent years by the ESC and by the EuropeanAssociation for Cardio-Thoracic Surgery (EACTS) as well as byother societies and organizations. Because of the impact on 216  ESC Guidelines D ownl   o a d  e d f  r  om h  t   t   p s :  /   /   a c  a d  emi   c . o u p. c  om /   e ur h  e ar  t   j   /   ar  t  i   c l   e- a b  s  t  r  a c  t   /   3  9  /   3  /  2 1  3  /  4  0  9  5  0 4  3  b  y  g u e s  t   on1 4 A  u g u s  t  2  0 1  9 
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