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Dual Antiplatelet Therapy Duration After the Placement of a Drug-Eluting Stent: What Are the Data?

  • Coronary Artery Disease (D Feldman, Section Editor)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Opinion statement

The data supporting the immediate use of dual antiplatelet therapy (DAPT) post implantation of drug-eluting stents (DESs) is irrefutable. DAPT in this early period is necessary to prevent stent thrombosis during endothelialization of the stent, a process known to be delayed when DESs are placed. In addition, DAPT helps prevent thrombosis from plaque rupture that occurs outside of the initial stented area and/or at neo-atherosclerotic lesions within a previously coated stent. The ACC/AHA current guidelines (Levine et al. J Am Coll Cardiol. 58(24):e44–122, 2011) recommend 12 months of DAPT post DES implantation. As the result of several randomized clinical trials (Task Force on Myocardial Revascularization of the European Society of Cardio-Thoracic Surgery (EACTS) et al. Eur Heart J. 31(20):2501–55, 2010) showing the safety of a shorter duration of DAPT, the European Heart Society altered their recommendations to 6–12 months of DAPT post DES implantation. However, recent data from the DAPT trial (Mauri et al. N Engl J Med. 371(23):2156–66, 2014) clearly demonstrated less ischemic events with 30 months of DAPT. This trial and others have established that an increased DAPT duration increases bleeding risk which, in turn, increases subsequent morbidity and mortality. The current conundrum lies in defining the optimal time of DAPT post DES to adequately reduce ischemic events while minimizing bleeding risks. Future studies are required to better stratify patients into low and high risk for both ischemic and bleeding risks to assess whether shorter or longer courses of DAPT are the most appropriate for any specific patients. Until then, instead of a “one size fits all” approach to patients who receive DESs, the treating physician must consider both procedural and patient factors when deciding the optimal duration of DAPT for each patient.

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References and Recommended Reading

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  1. Stettler C et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet. 2007;370(9591):937–48.

    Article  CAS  PubMed  Google Scholar 

  2. Kotani J et al. Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic findings. J Am Coll Cardiol. 2006;47(10):2108–11.

    Article  CAS  PubMed  Google Scholar 

  3. Nakazawa G et al. Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: an autopsy study. Circulation. 2008;118(11):1138–45.

    Article  PubMed  Google Scholar 

  4. Ueda Y et al. Neointimal coverage of stents in human coronary arteries observed by angioscopy. J Am Coll Cardiol. 1994;23(2):341–6.

    Article  CAS  PubMed  Google Scholar 

  5. Joner M et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol. 2006;48(1):193–202.

    Article  PubMed  Google Scholar 

  6. Chen ZM et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366(9497):1607–21.

    Article  CAS  PubMed  Google Scholar 

  7. Mehta SR et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001;358(9281):527–33.

    Article  CAS  PubMed  Google Scholar 

  8. Sabatine MS et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA. 2005;294(10):1224–32.

    Article  CAS  PubMed  Google Scholar 

  9. Yusuf S et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345(7):494–502.

    Article  CAS  PubMed  Google Scholar 

  10. Butler MJ et al. The effect of intended duration of clopidogrel use on early and late mortality and major adverse cardiac events in patients with drug-eluting stents. Am Heart J. 2009;157(5):899–907.

    Article  CAS  PubMed  Google Scholar 

  11. Eisenstein EL et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA. 2007;297(2):159–68.

    Article  CAS  PubMed  Google Scholar 

  12. Pfisterer M et al. Late 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 Cardiol. 2006;48(12):2584–91.

    Article  CAS  PubMed  Google Scholar 

  13. van Werkum JW et al. Predictors of coronary stent thrombosis: the Dutch Stent Thrombosis Registry. J Am Coll Cardiol. 2009;53(16):1399–409.

    Article  PubMed  Google Scholar 

  14. Levine GN et al. 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. J Am Coll Cardiol. 2011;58(24):e44–122.

    Article  PubMed  Google Scholar 

  15. Wijns W et al. Task Force on Myocardial Revascularization of the European Society of Cardio-Thoracic Surgery (EACTS) et al. Guidelines on myocardial revascularization. Eur Heart J. 2010;31(20):2501–55.

  16. Iwata Y et al. Incidence of premature discontinuation of antiplatelet therapy after sirolimus-eluting stent implantation. Circ J. 2008;72(2):340–1.

    Article  PubMed  Google Scholar 

  17. Spertus JA et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation. 2006;113(24):2803–9.

    Article  CAS  PubMed  Google Scholar 

  18. Varenhorst C et al. Duration of dual antiplatelet treatment with clopidogrel and aspirin in patients with acute coronary syndrome. Eur Heart J. 2014;35(15):969–78.

    Article  CAS  PubMed  Google Scholar 

  19. Kedhi E et al. Stent thrombosis: insights on outcomes, predictors and impact of dual antiplatelet therapy interruption from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE trials. Eur Interv. 2012;8(5):599–606.

    Google Scholar 

  20. Park SJ et al. Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med. 2010;362(15):1374–82.

    Article  CAS  PubMed  Google Scholar 

  21. Valgimigli M et al. Short- versus long-term duration of dual-antiplatelet therapy after coronary stenting: a randomized multicenter trial. Circulation. 2012;125(16):2015–26.

    Article  CAS  PubMed  Google Scholar 

  22. Lee CW et al. Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial. Circulation. 2014;129(3):304–12.

    Article  CAS  PubMed  Google Scholar 

  23. Galper BZ, Mauri L. Antiplatelet therapy after coronary stenting. Curr Treat Options Cardiovasc Med. 2013;15(1):1–10. A review article making the observation that prolonging dual antiplatelet therapy seemed to improve the outcomes of the patients involved and that while newer agents such as ticagrelor and prasugrel seem more effective in diminishing the risk of cardiac events post PCI, they have been associated with higher chances of bleeding. They recommend that until larger and better-powered studies are available to evaluate stent thrombosis, myocardial infarction, bleeding and death, dual antiplatelet therapy ought to be used for at the least 6 to 12 months. They also question whether duration of therapy should or will be dependent on the nature of newer generation stents.

  24. Mauri L et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371(23):2156–66. This is the first published double-blinded, randomized controlled trial, powered to evaluate if dual antiplatelet therapy post drug-eluting stent placement demonstrates a reduced risk of stent thrombosis or myocardial ischemic event. It demonstrated statistically significant reduction in stent thrombosis and major cardiovascular events, with an increased moderate-severe risk of bleeding and mortality with prolonged dual antiplatelet therapy.

    Article  Google Scholar 

  25. Colombo A, Chieffo A. Dual antiplatelet therapy after drug-eluting stents—how long to treat? N Engl J Med. 2014;371(23):2225–6. An editorial accompanying and summarizing the DAPT study, questions whether there is in fact “mandatory” and “possibly beneficial” periods post drug-eluting stent placement for dual antiplatelet therapy. Recommendations included individualization of DAPT duration given increased mortality and bleeding risk with prolonged therapy despite lower rates of stent thrombosis.

    Article  CAS  PubMed  Google Scholar 

  26. Garratt KN et al. Prasugrel plus aspirin beyond 12 months is associated with improved outcomes after taxus liberte paclitaxel-eluting coronary stent placement. Circulation. 2014;313(1):62–73.

    Google Scholar 

  27. Fiedler KA et al. Randomised, double-blind trial on the value of tapered discontinuation of clopidogrel maintenance therapy after drug-eluting stent implantation. Intracoronary Stenting and Antithrombotic Regimen: CAUTION in Discontinuing Clopidogrel Therapy—ISAR-CAUTIO. Thromb Haemost. 2014;111(6):1041–9. Double-blinded, randomized controlled trial to assess abrupt discontinuation of clopidogrel vs. gradual 4-week taper, 90 days after the drug-eluting stent had been placed. This trial was stopped prematurely as a result of slow enrollment, attributed to the lack of routine follow-up at the time of discontinuation, and no significant difference was noted in composite of cardiac death, myocardial infarction, stent thrombosis, stroke, major bleed, or ACS requiring re-hospitalization.

  28. Gwon HC et al. Six-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. Circulation. 2012;125(3):505–13.

    Article  CAS  PubMed  Google Scholar 

  29. Kim BK et al. A 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 Cardiol. 2012;60(15):1340–8.

    Article  CAS  PubMed  Google Scholar 

  30. Camenzind E et al. Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial. Lancet. 2012;380(9851):1396–405.

  31. Feres F et al. Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510–22.

    CAS  PubMed  Google Scholar 

  32. Gilard M, et al. Six-month versus 24-month dual antiplatelet therapy after implantation of drug eluting stents in patients non-resistant to aspirin: ITALIC, a randomized multicenter trial. J Am Coll Cardiol. 2014.

  33. El-Hayek G et al. Meta-analysis of randomized clinical trials comparing short-term versus long-term dual antiplatelet therapy following drug-eluting stents. Am J Cardiol. 2014;114(2):236–42. Meta-analysis of randomized controlled trials comparing short (<6 months) vs. long (≥12 months) duration dual antiplatelet therapy after drug-eluting stent placement, with close attention to the EXCELLENT, RESET, PRODIGY, and OPTIMIZE trials. A higher, albeit non-significant, rate of stent thrombosis in the shorter duration group was noted, and no significant difference in adverse cardiac events was demonstrated; there was a significant increased risk of major bleeding with the prolonged group. In several of the trials, stent thrombosis was noted to occur early in the course of the study, thus making them unable to attribute the events to short duration of DAPT.

  34. Dafni U. Landmark analysis at the 25-year landmark point. Circ Cardiovasc Qual Outcomes. 2011;4(3):363–71.

    Article  PubMed  Google Scholar 

  35. Colombo A et al. Second generation drug-eluting stents implantation followed by six versus twelve-month—dual antiplatelet therapy- the SECURITY randomized clinical trial. J Am Coll Cardiol. 2014;64(20):2086–97.

    Article  CAS  PubMed  Google Scholar 

  36. Holmes Jr DR. Art and science. J Am Coll Cardiol. 2014;64(20):2098–100.

    Article  PubMed  Google Scholar 

  37. Byrne RA et al. Rationale and design of a randomized, double-blind, placebo-controlled trial of 6 versus 12 months clopidogrel therapy after implantation of a drug-eluting stent: the Intracoronary Stenting and Antithrombotic Regimen: Safety And EFficacy of 6 Months Dual Antiplatelet Therapy After Drug-Eluting Stenting (ISAR-SAFE) study. Am Heart J. 2009;157(4):620–4 e2.

  38. Iakovou I et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005;293(17):2126–30.

    Article  CAS  PubMed  Google Scholar 

  39. Kuchulakanti PK et al. Correlates and long-term outcomes of angiographically proven stent thrombosis with sirolimus- and paclitaxel-eluting stents. Circulation. 2006;113(8):1108–13.

    Article  CAS  PubMed  Google Scholar 

  40. Ong AT et al. Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after bare-metal, sirolimus, or paclitaxel stent implantation. J Am Coll Cardiol. 2005;45(6):947–53.

    Article  CAS  PubMed  Google Scholar 

  41. Park DW et al. Frequency of and risk factors for stent thrombosis after drug-eluting stent implantation during long-term follow-up. Am J Cardiol. 2006;98(3):352–6.

    Article  PubMed  Google Scholar 

  42. Kastrati A, et al. Intracoronary stenting and angiographic results strut thickness effect on restenosis outcome (ISAR-STEREO) Trial. Vestn Rentgenol Radiol. 2012;(2):52–60.

  43. Kereiakes DJ et al. Thrombosis and drug-eluting stents: a critical appraisal. Rev Cardiovasc Med. 2004;5(1):9–15.

    Article  PubMed  Google Scholar 

  44. Orford JL et al. Frequency and correlates of coronary stent thrombosis in the modern era: analysis of a single center registry. J Am Coll Cardiol. 2002;40(9):1567–72.

    Article  PubMed  Google Scholar 

  45. Silva JA et al. Primary stenting in acute myocardial infarction: influence of diabetes mellitus in angiographic results and clinical outcome. Am Heart J. 1999;138(3 Pt 1):446–55.

    Article  CAS  PubMed  Google Scholar 

  46. Roy P et al. The potential clinical utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention with drug-eluting stents. Eur Heart J. 2008;29(15):1851–7.

    Article  CAS  PubMed  Google Scholar 

  47. Doostzadeh J et al. Recent progress in percutaneous coronary intervention: evolution of the drug-eluting stents, focus on the XIENCE V drug-eluting stent. Coron Artery Dis. 2010;21(1):46–56.

    Article  PubMed  Google Scholar 

  48. Lange RA, Hillis LD. Second-generation drug-eluting coronary stents. N Engl J Med. 2010;362(18):1728–30.

    Article  CAS  PubMed  Google Scholar 

  49. Valgimigli M et al. Should 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 J. 2013;34(12):909–19.

    Article  CAS  PubMed  Google Scholar 

  50. Wallentin L et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–57.

    Article  CAS  PubMed  Google Scholar 

  51. Wiviott SD et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–15.

    Article  CAS  PubMed  Google Scholar 

  52. Helft G et al. Efficacy and safety of 12 versus 48 months of dual antiplatelet therapy after implantation of a drug-eluting stent: the OPTImal DUAL antiplatelet therapy (OPTIDUAL) trial: study protocol for a randomized controlled trial. Trials. 2013;14:56. The results of this study are still not published; however, what differentiates this study from DAPT apart from duration of the prolonged arm which was 30 months with DAPT is the exclusion of patients with known malignancy; in DAPT, there was a high rate of cancer-related deaths with the prolonged therapy group, which significantly decreased when these patients were excluded in post hoc analysis.

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Dr. Jad Raffoul and Dr. Andrew J.P. Klein each declare no potential conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Department of Internal Medicine, Saint Louis University School of Medicine, 1402 South Grand Blvd., Saint Louis, MO, 63104, USA

    Jad Raffoul MD & Andrew J. P. Klein MD, FACC, FSCAI

  2. Department of Internal Medicine, Division of Cardiology, St. Louis VA Healthcare System - The John Cochran VA Medical Center, 915 North Grand Blvd., Saint Louis, MO, 63106, USA

    Andrew J. P. Klein MD, FACC, FSCAI

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  1. Jad Raffoul MD
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Correspondence to Andrew J. P. Klein MD, FACC, FSCAI.

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Raffoul, J., Klein, A.J.P. Dual Antiplatelet Therapy Duration After the Placement of a Drug-Eluting Stent: What Are the Data?. Curr Treat Options Cardio Med 17, 11 (2015). https://doi.org/10.1007/s11936-015-0367-0

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