Reviews21 July 2015
A Systematic Review and Meta-analysis
    Author, Article, and Disclosure Information



    The appropriate duration of dual-antiplatelet therapy (DAPT) after drug-eluting stent (DES) placement remains controversial.


    To summarize data on clinical outcomes with longer- versus shorter-duration DAPT after DES placement in adults with coronary artery disease.

    Data Sources:

    Ovid MEDLINE and EMBASE, 1996 to 27 March 2015, and manual screening of references.

    Study Selection:

    Randomized, controlled trials comparing longer- versus shorter-duration DAPT after DES placement.

    Data Extraction:

    Two reviewers screened potentially eligible articles; extracted data on populations, interventions, and outcomes; assessed risk of bias; and used the Grading of Recommendations Assessment, Development and Evaluation guidelines to rate overall confidence in effect estimates.

    Data Synthesis:

    Among 1010 articles identified, 9 trials including 29 531 patients were eligible; data were complete for 28 808 patients. Moderate-quality evidence showed that longer-duration DAPT decreased risk for myocardial infarction (risk ratio [RR], 0.73 [95% CI, 0.58 to 0.92]) and increased mortality (RR, 1.19 [CI, 1.04 to 1.36]). High-quality evidence showed that DAPT increased risk for major bleeding (RR, 1.63 [CI, 1.34 to 1.99]).


    Confidence in estimates were decreased owing to imprecision for most outcomes (particularly myocardial infarction), risk of bias from limited blinding in 7 of 9 studies, indirectness due to variability in use of first- and second-generation stents, and off-protocol use of DAPT in some studies.


    Extended DAPT is associated with approximately 8 fewer myocardial infarctions per 1000 treated patients per year but 6 more major bleeding events than shorter-duration DAPT. Because absolute effects are very small and closely balanced, decisions regarding the duration of DAPT therapy must take into account patients' values and preference.

    Primary Funding Source:



    • 1. Fajadet JWijns WLaarman GJKuck KHOrmiston JMünzel Tet alENDEAVOR II InvestigatorsRandomized, double-blind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial. Circulation2006;114:798-806. [PMID: 16908773] CrossrefMedlineGoogle Scholar
    • 2. Moses JWLeon MBPopma JJFitzgerald PJHolmes DRO'Shaughnessy Cet alSIRIUS InvestigatorsSirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med2003;349:1315-23. [PMID: 14523139] CrossrefMedlineGoogle Scholar
    • 3. Stone GWEllis SGCox DAHermiller JO'Shaughnessy CMann JTet alTAXUS-IV InvestigatorsA polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med2004;350:221-31. [PMID: 14724301] CrossrefMedlineGoogle Scholar
    • 4. Windecker SKolh PAlfonso FCollet JPCremer JFalk Vet alAuthors/Task Force members2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J2014;35:2541-619. [PMID: 25173339] doi:10.1093/eurheartj/ehu278 CrossrefMedlineGoogle Scholar
    • 5. Levine GNBates ERBlankenship JCBailey SRBittl JACercek Bet al2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation2011;124:e574-651. [PMID: 22064601] doi:10.1161/CIR.0b013e31823ba622 CrossrefMedlineGoogle Scholar
    • 6. Vandvik POLincoff AMGore JMGutterman DDSonnenberg FAAlonso-Coello Pet alAmerican College of Chest PhysiciansPrimary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest2012;141:e637S-68S. [PMID: 22315274] doi:10.1378/chest.11-2306 CrossrefMedlineGoogle Scholar
    • 7. Daemen JWenaweser PTsuchida KAbrecht LVaina SMorger Cet alEarly and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet2007;369:667-78. [PMID: 17321312] CrossrefMedlineGoogle Scholar
    • 8. Eisenstein ELAnstrom KJKong DFShaw LKTuttle RHMark DBet alClopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA2007;297:159-68. [PMID: 17148711] CrossrefMedlineGoogle Scholar
    • 9. Pfisterer MBrunner-LaRocca HPBuser PTRickenbacher PHunziker PMueller Cet alBASKET-LATE InvestigatorsLate clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol2006;48:2584-91. [PMID: 17174201] CrossrefMedlineGoogle Scholar
    • 10. Faxon DPLawler EYoung MGaziano MKinlay SProlonged clopidogrel use after bare metal and drug-eluting stent placement: the Veterans Administration drug-eluting stent study. Circ Cardiovasc Interv2012;5:372-80. [PMID: 22668555] doi:10.1161/CIRCINTERVENTIONS.111.967257 CrossrefMedlineGoogle Scholar
    • 11. Collet JPSilvain JBarthélémy ORangé GCayla GVanBelle Eet alARCTIC investigatorsDual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Lancet2014;384:1577-85. [PMID: 25037988] doi:10.1016/S0140-6736(14)60612-7 CrossrefMedlineGoogle Scholar
    • 12. Feres FCosta RAAbizaid ALeon MBMarin-Neto JABotelho RVet alOPTIMIZE Trial InvestigatorsThree vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA2013;310:2510-22. [PMID: 24177257] doi:10.1001/jama.2013.282183 CrossrefMedlineGoogle Scholar
    • 13. Gwon HCHahn JYPark KWSong YBChae IHLim DSet alSix-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study. Circulation2012;125:505-13. [PMID: 22179532] doi:10.1161/CIRCULATIONAHA.111.059022 CrossrefMedlineGoogle Scholar
    • 14. Lee CWAhn JMPark DWKang SJLee SWKim YHet alOptimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial. Circulation2014;129:304-12. [PMID: 24097439] doi:10.1161/CIRCULATIONAHA.113.003303 CrossrefMedlineGoogle Scholar
    • 15. Park SJPark DWKim YHKang SJLee SWLee CWet alDuration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med2010;362:1374-82. [PMID: 20231231] doi:10.1056/NEJMoa1001266 CrossrefMedlineGoogle Scholar
    • 16. Valgimigli MBorghesi MTebaldi MVranckx PParrinello GFerrari RPROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY InvestigatorsShould duration of dual antiplatelet therapy depend on the type and/or potency of implanted stent? A pre-specified analysis from the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY). Eur Heart J2013;34:909-19. [PMID: 23315904] doi:10.1093/eurheartj/ehs460 CrossrefMedlineGoogle Scholar
    • 17. Mauri LKereiakes DJYeh RWDriscoll-Shempp PCutlip DESteg PGet alDAPT Study InvestigatorsTwelve or 30 monthsj of dual antiplatelet therapy after drug-eluting stents. N Engl J Med2014;371:2155-66. [PMID: 25399658] doi:10.1056/NEJMoa1409312 CrossrefMedlineGoogle Scholar
    • 18. Ferreira-González IBusse JWHeels-Ansdell DMontori VMAkl EABryant DMet alProblems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials. BMJ2007;334:786. [PMID: 17403713] CrossrefMedlineGoogle Scholar
    • 19. Lim EBrown AHelmy AMussa SAltman DGComposite outcomes in cardiovascular research: a survey of randomized trials. Ann Intern Med2008;149:612-7. [PMID: 18981486] LinkGoogle Scholar
    • 20. Higgins JPAltman DGGøtzsche PCJüni PMoher DOxman ADet alCochrane Bias Methods GroupThe Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ2011;343:d5928. [PMID: 22008217] doi:10.1136/bmj.d5928 CrossrefMedlineGoogle Scholar
    • 21. Guyatt GHOxman ADVist GEKunz RFalck-Ytter YAlonso-Coello Pet alGRADE Working GroupGRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ2008;336:924-6. [PMID: 18436948] doi:10.1136/bmj.39489.470347.AD CrossrefMedlineGoogle Scholar
    • 22. Guyatt GHOxman ADVist GKunz RBrozek JAlonso-Coello Pet alGRADE guidelines: 4. Rating the quality of evidence—study limitations (risk of bias). J Clin Epidemiol2011;64:407-15. [PMID: 21247734] doi:10.1016/j.jclinepi.2010.07.017 CrossrefMedlineGoogle Scholar
    • 23. Guyatt GHOxman ADKunz RBrozek JAlonso-Coello PRind Det alGRADE guidelines 6. Rating the quality of evidence—imprecision. J Clin Epidemiol2011;64:1283-93. [PMID: 21839614] doi:10.1016/j.jclinepi.2011.01.012 CrossrefMedlineGoogle Scholar
    • 24. Guyatt GHOxman ADKunz RWoodcock JBrozek JHelfand Met alGRADE Working GroupGRADE guidelines: 7. Rating the quality of evidence—inconsistency. J Clin Epidemiol2011;64:1294-302. [PMID: 21803546] doi:10.1016/j.jclinepi.2011.03.017 CrossrefMedlineGoogle Scholar
    • 25. Guyatt GHOxman ADKunz RWoodcock JBrozek JHelfand Met alGRADE Working GroupGRADE guidelines: 8. Rating the quality of evidence—indirectness. J Clin Epidemiol2011;64:1303-10. [PMID: 21802903] doi:10.1016/j.jclinepi.2011.04.014 CrossrefMedlineGoogle Scholar
    • 26. Guyatt GHOxman ADMontori VVist GKunz RBrozek Jet alGRADE guidelines: 5. Rating the quality of evidence—publication bias. J Clin Epidemiol2011;64:1277-82. [PMID: 21802904] doi:10.1016/j.jclinepi.2011.01.011 CrossrefMedlineGoogle Scholar
    • 27. Akl EAJohnston BCAlonso-Coello PNeumann IEbrahim SBriel Met alAddressing dichotomous data for participants excluded from trial analysis: a guide for systematic reviewers. PLoS One2013;8:e57132. [PMID: 23451162] doi:10.1371/journal.pone.0057132 CrossrefMedlineGoogle Scholar
    • 28. Akl EABriel MYou JJSun XJohnston BCBusse JWet alPotential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review. BMJ2012;344:e2809. [PMID: 22611167] doi:10.1136/bmj.e2809 CrossrefMedlineGoogle Scholar
    • 29. Kim BKHong MKShin DHNam CMKim JSKo YGet alRESET InvestigatorsA new strategy for discontinuation of dual antiplatelet therapy: the RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation). J Am Coll Cardiol2012;60:1340-8. [PMID: 22999717] doi:10.1016/j.jacc.2012.06.043 CrossrefMedlineGoogle Scholar
    • 30. Gilard MBarragan PNoryani AANoor HAMajwal THovasse Tet al6- versus 24-month dual antiplatelet therapy after implantation of drug-eluting stents in patients nonresistant to aspirin: the randomized, multicenter ITALIC trial. J Am Coll Cardiol2015;65:777-86. [PMID: 25461690] doi:10.1016/j.jacc.2014.11.008 CrossrefMedlineGoogle Scholar
    • 31. Borenstein MHHedges LVHiggins JPTRothstein HRIntroduction to Meta-analysis. Chichester, United Kingdom: J Wiley; 2008. Google Scholar
    • 32. IntHout JIoannidis JPBorm GFThe Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method. BMC Med Res Methodol2014;14:25. [PMID: 24548571] doi:10.1186/1471-2288-14-25 CrossrefMedlineGoogle Scholar
    • 33. Colombo AChieffo AFrasheri AGarbo RMasotti-Centol MSalvatella Net alSecond-generation drug-eluting stent implantation followed by 6- versus 12-month dual antiplatelet therapy: the SECURITY randomized clinical trial. J Am Coll Cardiol2014;64:2086-97. [PMID: 25236346] doi:10.1016/j.jacc.2014.09.008 CrossrefMedlineGoogle Scholar
    • 34. Schulz-Schüpke SByrne RATen Berg JMNeumann FJHan YAdriaenssens Tet alon behalf of the Intracoronary Stenting and Antithrombotic Regimen: Safety And EFficacy of 6 Months Dual Antiplatelet Therapy After Drug-Eluting Stenting (ISAR-SAFE) trial investigators.ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 versus 12 months of clopidogrel therapy after drug-eluting stenting. Eur Heart J2015. [PMID: 25616646] CrossrefMedlineGoogle Scholar
    • 35. Kirtane AJGupta AIyengar SMoses JWLeon MBApplegate Ret alSafety and efficacy of drug-eluting and bare metal stents: comprehensive meta-analysis of randomized trials and observational studies. Circulation2009;119:3198-206. [PMID: 19528338] doi:10.1161/CIRCULATIONAHA.108.826479 CrossrefMedlineGoogle Scholar
    • 36. Kirtane AJLeon MBBall MWBajwa HSSketch MHColeman PSet alENDEAVOR IV InvestigatorsThe "final" 5-year follow-up from the ENDEAVOR IV trial comparing a zotarolimus-eluting stent with a paclitaxel-eluting stent. JACC Cardiovasc Interv2013;6:325-33. [PMID: 23523453] doi:10.1016/j.jcin.2012.12.123 CrossrefMedlineGoogle Scholar
    • 37. Stone GWRizvi ANewman WMastali KWang JCCaputo Ret alSPIRIT IV InvestigatorsEverolimus-eluting versus paclitaxel-eluting stents in coronary artery disease. N Engl J Med2010;362:1663-74. [PMID: 20445180] doi:10.1056/NEJMoa0910496 CrossrefMedlineGoogle Scholar
    • 38. Palmerini TBenedetto UBacchi-Reggiani LRiva DDBiondi-Zoccai GFeres Fet alMortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials. Lancet2015. [PMID: 25777667] doi:10.1016/S0140-6736(15)60263-X CrossrefMedlineGoogle Scholar