Skip to main content
SpringerLink
Log in

Dual Antiplatelet Therapy Duration: Reconciling the Inconsistencies

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Dual antiplatelet therapy (DAPT) prevents recurrent ischemic events after an acute coronary syndrome (ACS) as well as stent thrombosis (ST) in patients with prior stent implantation. Nevertheless, these benefits are counterbalanced by a significant bleeding hazard, which is directly related to the treatment duration. Although DAPT has been extensively studied in numerous clinical trials, optimal treatment duration is still debated, mostly because of apparent inconsistencies among studies. Shortened treatment duration of 6 or 3 months was shown to mitigate bleeding risk compared with consensus-grounded 12-month standard duration, without any apparent excess of ischemic events. However, recent trials showed that a >12-month course of treatment reduces ischemic events but increases bleeding compared with 12 months. The inconsistent benefit of a longer DAPT course compared with shorter treatment durations is puzzling, and requires a careful appraisal of between-studies differences. We sought to summarize the existing evidence aiming at reconciling apparent inconsistencies among these studies, as well as thoroughly discuss the possible increased risk of fatal events associated with long-term DAPT. Benefits and risks of prolonging or shortening DAPT duration will be discussed, with a focus on treatment individualization. Finally, we will provide an outlook for possible future directions in the field.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Schomig A, Neumann FJ, Kastrati A, Schuhlen H, Blasini R, Hadamitzky M, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med. 1996;334(17):1084–9. doi:10.1056/NEJM199604253341702.

    Article  CAS  PubMed  Google Scholar 

  2. Valgimigli M, Ariotti S, Costa F. Duration of dual antiplatelet therapy after drug-eluting stent implantation: will we ever reach a consensus? Eur Heart J. 2015;36(20):1219–22. doi:10.1093/eurheartj/ehv053.

    Article  CAS  PubMed  Google Scholar 

  3. Navarese EP, Andreotti F, Schulze V, Kolodziejczak M, Buffon A, Brouwer M, et al. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. BMJ. 2015;350:h1618. doi:10.1136/bmj.h1618.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C, et al. Short- versus long-term duration of dual-antiplatelet therapy after coronary stenting: a randomized multicenter trial. Circulation. 2012;125(16):2015–26. doi:10.1161/CIRCULATIONAHA.111.071589.

    Article  CAS  PubMed  Google Scholar 

  5. Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371(23):2155–66. doi:10.1056/NEJMoa1409312.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Authors/Task Force m, Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, et al. 2014 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 J. 2014;35(37):2541–619. doi:10.1093/eurheartj/ehu278.

  7. Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016;68(10):1082–115. doi:10.1016/j.jacc.2016.03.513.

    Article  PubMed  Google Scholar 

  8. Valgimigli M, Gargiulo G. Deciding on the duration of dual antiplatelet therapy-when the choice between 2 evils is still evil. JAMA Cardiol. 2017. doi:10.1001/jamacardio.2017.0125.

    Google Scholar 

  9. Palmerini T, Della Riva D, Benedetto U, Bacchi Reggiani L, Feres F, Abizaid A, et al. Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11,473 patients. Eur Heart J. 2017. doi:10.1093/eurheartj/ehw627.

    PubMed  Google Scholar 

  10. Ariotti S, Gargiulo G, Valgimigli M. Long-term use of ticagrelor in patients with coronary artery disease. Curr Cardiol Rep. 2017;19(1):2. doi:10.1007/s11886-017-0810-9.

    Article  PubMed  Google Scholar 

  11. Leon MB, Baim DS, Popma JJ, Gordon PC, Cutlip DE, Ho KK, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. N Engl J Med. 1998;339(23):1665–71.

    Article  CAS  PubMed  Google Scholar 

  12. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK, 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. doi:10.1056/NEJMoa010746.

    Article  CAS  PubMed  Google Scholar 

  13. Stone GW, Ellis SG, Cox DA, Hermiller J, O’Shaughnessy C, Mann JT, et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med. 2004;350(3):221–31. doi:10.1056/NEJMoa032441.

    Article  CAS  PubMed  Google Scholar 

  14. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–15. doi:10.1056/NEJMoa0706482.

    Article  CAS  PubMed  Google Scholar 

  15. Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med. 2002;346(23):1773–80. doi:10.1056/NEJMoa012843.

    Article  CAS  PubMed  Google Scholar 

  16. Camenzind E, Steg PG, Wijns W. Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. Circulation. 2007;115(11):1440–55. doi:10.1161/CIRCULATIONAHA.106.666800 (discussion 55).

  17. American Food and Drug Administration. FDA Clinical Overview for Panel Packet DES Thrombosis Panel. 2006. https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4253b1_01.pdf. Accessed 4 Apr 2017.

  18. McFadden EP, Stabile E, Regar E, Cheneau E, Ong AT, Kinnaird T, et al. Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet. 2004;364(9444):1519–21. doi:10.1016/S0140-6736(04)17275-9.

    Article  CAS  PubMed  Google Scholar 

  19. Task Force on Myocardial Revascularization of the European Society of C, The European Association for Cardio-Thoracic S, European Association for Percutaneous Cardiovascular I, Kolh P, Wijns W, Danchin N, et al. Guidelines on myocardial revascularization. Eur J Cardio Thorac Surg. 2010;38 Suppl:S1–52. doi:10.1016/j.ejcts.2010.08.019.

  20. Wijns W, Steg PG, Mauri L, Kurowski V, Parikh K, Gao R, et al. Endeavour zotarolimus-eluting stent reduces stent thrombosis and improves clinical outcomes compared with cypher sirolimus-eluting stent: 4-year results of the PROTECT randomized trial. Eur Heart J. 2014;35(40):2812–20. doi:10.1093/eurheartj/ehu318.

    Article  CAS  PubMed  Google Scholar 

  21. Serruys PW, Silber S, Garg S, van Geuns RJ, Richardt G, Buszman PE, et al. Comparison of zotarolimus-eluting and everolimus-eluting coronary stents. N Engl J Med. 2010;363(2):136–46. doi:10.1056/NEJMoa1004130.

    Article  CAS  PubMed  Google Scholar 

  22. Stone GW, Rizvi A, Newman W, Mastali K, Wang JC, Caputo R, et al. Everolimus-eluting versus paclitaxel-eluting stents in coronary artery disease. N Engl J Med. 2010;362(18):1663–74. doi:10.1056/NEJMoa0910496.

    Article  CAS  PubMed  Google Scholar 

  23. Valgimigli M, Sabate M, Kaiser C, Brugaletta S, de la Torre Hernandez JM, Galatius S, et al. Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: patient level meta-analysis. BMJ. 2014;349:g6427. doi:10.1136/bmj.g6427.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Costa F, Ariotti S, Valgimigli M, Kolh P, Windecker S, Task Force on Myocardial Revascularization of the European Society of C, et al. Perspectives on the 2014 ESC/EACTS guidelines on myocardial revascularization: fifty years of revascularization: where are we and where are we heading? J Cardiovasc Transl Res. 2015;8(4):211–20. doi:10.1007/s12265-015-9632-6.

  25. Bonaca MP, Braunwald E, Sabatine MS. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;373(13):1274–5. doi:10.1056/NEJMc1508692.

    PubMed  Google Scholar 

  26. Valgimigli M, Costa F, Byrne R, Haude M, Baumbach A, Windecker S. Dual antiplatelet therapy duration after coronary stenting in clinical practice: results of an EAPCI survey. EuroIntervention. 2015;11(1):68–74. doi:10.4244/EIJV11I1A11.

    Article  PubMed  Google Scholar 

  27. Feres F, Costa RA, Abizaid A, Leon MB, Marin-Neto JA, Botelho RV, et al. Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510–22. doi:10.1001/jama.2013.282183.

    CAS  PubMed  Google Scholar 

  28. Kim BK, Hong MK, Shin DH, Nam CM, Kim JS, Ko YG, 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. doi:10.1016/j.jacc.2012.06.043.

    Article  CAS  PubMed  Google Scholar 

  29. Schulz-Schupke S, Byrne RA, Ten Berg JM, Neumann FJ, Han Y, Adriaenssens T, et al. ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting. Eur Heart J. 2015;36(20):1252–63. doi:10.1093/eurheartj/ehu523.

    Article  PubMed  Google Scholar 

  30. Gwon HC, Hahn JY, Park KW, Song YB, Chae IH, Lim DS, 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. doi:10.1161/CIRCULATIONAHA.111.059022.

    Article  CAS  PubMed  Google Scholar 

  31. Colombo A, Chieffo A, Frasheri A, Garbo R, Masotti-Centol M, Salvatella N, et al. Second-generation drug-eluting stent implantation followed by 6- versus 12-month dual antiplatelet therapy: the SECURITY randomized clinical trial. J Am Coll Cardiol. 2014;64(20):2086–97. doi:10.1016/j.jacc.2014.09.008.

    Article  CAS  PubMed  Google Scholar 

  32. Han Y, Xu B, Xu K, Guan C, Jing Q, Zheng Q, et al. Six versus 12 months of dual antiplatelet therapy after implantation of biodegradable polymer sirolimus-eluting stent: randomized substudy of the I-LOVE-IT 2 Trial. Circ Cardiovasc Interv. 2016;9(2):e003145. doi:10.1161/CIRCINTERVENTIONS.115.003145.

    Article  CAS  PubMed  Google Scholar 

  33. Hong SJ, Shin DH, Kim JS, Kim BK, Ko YG, Choi D, et al. 6-month versus 12-month dual-antiplatelet therapy following long everolimus-eluting stent implantation: the IVUS-XPL Randomized Clinical Trial. JACC Cardiovasc Interv. 2016;9(14):1438–46. doi:10.1016/j.jcin.2016.04.036.

    Article  PubMed  Google Scholar 

  34. Ariotti S, Adamo M, Costa F, Patialiakas A, Briguori C, Thury A, et al. Is bare-metal stent implantation still justifiable in high bleeding risk patients undergoing percutaneous coronary intervention?: a pre-specified analysis from the ZEUS Trial. JACC Cardiovasc Interv. 2016;9(5):426–36. doi:10.1016/j.jcin.2015.11.015.

    Article  PubMed  Google Scholar 

  35. Valgimigli M, Patialiakas A, Thury A, McFadden E, Colangelo S, Campo G, et al. Zotarolimus-eluting versus bare-metal stents in uncertain drug-eluting stent candidates. J Am Coll Cardiol. 2015;65(8):805–15. doi:10.1016/j.jacc.2014.11.053.

    Article  CAS  PubMed  Google Scholar 

  36. Urban P, Meredith IT, Abizaid A, Pocock SJ, Carrie D, Naber C, et al. Polymer-free drug-coated coronary stents in patients at high bleeding risk. N Engl J Med. 2015;373(21):2038–47. doi:10.1056/NEJMoa1503943.

    Article  CAS  PubMed  Google Scholar 

  37. Gilard M, Barragan P, Noryani AA, Noor HA, Majwal T, Hovasse T, et al. 6- 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 Cardiol. 2015;65(8):777–86. doi:10.1016/j.jacc.2014.11.008.

    Article  CAS  PubMed  Google Scholar 

  38. Nakamura M, Ako R, Shinke J, Okada T, Ando Y, Anzai K, Tanaka H, Ueda YT, Nishida S, Ohira Y, Kawaguchi KK, Niinuma M, Omiya H, Morita TZ, Yasaka K, Inoue Y, Ishiwata K, Ochiai MH, Yokoi H. 6 months versus 18 months dual antiplatelet treatment for patients underwent bioabsorbable polymer and abluminal coated DES deployment: NIPPON randomized study. Rome: European Society of Cardiology Scientific Session; 2016.

  39. Nakamura M, Iijima R, Ako J, Shinke T, Okada H, Ito Y, et al. Dual antiplatelet therapy for 6 versus 18 months after biodegradable polymer drug-eluting stent implantation. JACC Cardiovasc Interv. 2017;10(12):1189–98. doi:10.1016/j.jcin.2017.04.019.

    Article  PubMed  Google Scholar 

  40. Collet JP, Silvain J, Barthelemy O, Range G, Cayla G, Van Belle E, et al. Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Lancet. 2014;384(9954):1577–85. doi:10.1016/S0140-6736(14)60612-7.

    Article  CAS  PubMed  Google Scholar 

  41. Helft G, Steg PG, Le Feuvre C, Georges JL, Carrie D, Dreyfus X, et al. Stopping or continuing clopidogrel 12 months after drug-eluting stent placement: the OPTIDUAL randomized trial. Eur Heart J. 2016;37(4):365–74. doi:10.1093/eurheartj/ehv481.

    PubMed  Google Scholar 

  42. Lee CW, Ahn JM, Park DW, Kang SJ, Lee SW, Kim YH, et al. Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: a randomized, controlled trial. Circulation. 2014;129(3):304–12. doi:10.1161/CIRCULATIONAHA.113.003303.

    Article  CAS  PubMed  Google Scholar 

  43. Collet JP, Cuisset T, Range G, Cayla G, Elhadad S, Pouillot C, et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med. 2012;367(22):2100–9. doi:10.1056/NEJMoa1209979.

    Article  CAS  PubMed  Google Scholar 

  44. Palmerini T, Benedetto U, Bacchi-Reggiani L, Della Riva D, Biondi-Zoccai G, Feres F, et al. Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials. Lancet. 2015;385(9985):2371–82. doi:10.1016/S0140-6736(15)60263-X.

    Article  CAS  PubMed  Google Scholar 

  45. Bittl JA, Baber U, Bradley SM, Wijeysundera DN. Duration of dual antiplatelet therapy: a systematic review for the 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016;68(10):1116–39. doi:10.1016/j.jacc.2016.03.512.

    Article  PubMed  Google Scholar 

  46. Hermiller JB, Krucoff MW, Kereiakes DJ, Windecker S, Steg PG, Yeh RW, et al. Benefits and risks of extended dual antiplatelet therapy after everolimus-eluting stents. JACC Cardiovasc Interv. 2016;9(2):138–47. doi:10.1016/j.jcin.2015.10.001.

    Article  PubMed  Google Scholar 

  47. Mauri L, Elmariah S, Yeh RW, Cutlip DE, Steg PG, Windecker S, et al. Causes of late mortality with dual antiplatelet therapy after coronary stents. Eur Heart J. 2016;37(4):378–85. doi:10.1093/eurheartj/ehv614.

    PubMed  Google Scholar 

  48. Costa F, Valgimigli M. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;373(13):1271–2. doi:10.1056/NEJMc1508692#SA2.

    Article  PubMed  Google Scholar 

  49. US Food and Drug Administration. FDA Drug Safety Communication: FDA review finds long-term treatment with blood-thinning medicine Plavix (clopidogrel) does not change risk of death. 2015. http://www.fda.gov/Drugs/DrugSafety/ucm471286.htm. Access 1 Jan 2017.

  50. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):1706–17. doi:10.1056/NEJMoa060989.

    Article  CAS  PubMed  Google Scholar 

  51. Bhatt DL, Flather MD, Hacke W, Berger PB, Black HR, Boden WE, et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007;49(19):1982–8. doi:10.1016/j.jacc.2007.03.025.

    Article  PubMed  Google Scholar 

  52. Bonaca MP, Bhatt DL, Steg PG, Storey RF, Cohen M, Im K, et al. Ischaemic risk and efficacy of ticagrelor in relation to time from P2Y12 inhibitor withdrawal in patients with prior myocardial infarction: insights from PEGASUS-TIMI 54. Eur Heart J. 2016;37(14):1133–42. doi:10.1093/eurheartj/ehv531.

    Article  PubMed  Google Scholar 

  53. Valgimigli M, Borghesi M, Tebaldi M, Vranckx P, Parrinello G, Ferrari R. 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. doi:10.1093/eurheartj/ehs460.

    Article  CAS  PubMed  Google Scholar 

  54. Palmerini T, Biondi-Zoccai G, Della Riva D, Stettler C, Sangiorgi D, D’Ascenzo F, et al. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet. 2012;379(9824):1393–402. doi:10.1016/S0140-6736(12)60324-9.

    Article  CAS  PubMed  Google Scholar 

  55. Sabate M, Brugaletta S, Cequier A, Iniguez A, Serra A, Jimenez-Quevedo P, et al. Clinical outcomes in patients with ST-segment elevation myocardial infarction treated with everolimus-eluting stents versus bare-metal stents (EXAMINATION): 5-year results of a randomised trial. Lancet. 2016;387(10016):357–66. doi:10.1016/S0140-6736(15)00548-6.

    Article  PubMed  Google Scholar 

  56. Bonaa KH, Mannsverk J, Wiseth R, Aaberge L, Myreng Y, Nygard O, et al. Drug-eluting or bare-metal stents for coronary artery disease. N Engl J Med. 2016;375(13):1242–52. doi:10.1056/NEJMoa1607991.

    Article  CAS  PubMed  Google Scholar 

  57. Crimi G, Leonardi S, Costa F, Adamo M, Ariotti S, Valgimigli M. Role of stent type and of duration of dual antiplatelet therapy in patients with chronic kidney disease undergoing percutaneous coronary interventions. Is bare metal stent implantation still a justifiable choice? A post-hoc analysis of the all comer PRODIGY trial. Int J Cardiol. 2016;212:110–7. doi:10.1016/j.ijcard.2016.03.033.

    Article  PubMed  Google Scholar 

  58. Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372(19):1791–800. doi:10.1056/NEJMoa1500857.

    Article  PubMed  Google Scholar 

  59. Valgimigli M, Costa F, Lokhnygina Y, Clare R, Wallentin L, Moliterno D, et al. Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial. Eur Heart J. 2016:ehw525. doi:10.1093/eurheartj/ehw525.

  60. Wiviott SD, Braunwald E, Angiolillo DJ, Meisel S, Dalby AJ, Verheugt FW, et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38. Circulation. 2008;118(16):1626–36. doi:10.1161/CIRCULATIONAHA.108.791061.

    Article  CAS  PubMed  Google Scholar 

  61. Costa F, Adamo M, Ariotti S, Ferrante G, Navarese EP, Leonardi S, et al. Left main or proximal left anterior descending coronary artery disease location identifies high-risk patients deriving potentially greater benefit from prolonged dual antiplatelet therapy duration. EuroIntervention. 2016;11(11):e1222–30. doi:10.4244/EIJY15M08_04.

    Article  PubMed  Google Scholar 

  62. Gurwitz JH, Goldberg RJ. Age-based exclusions from cardiovascular clinical trials: implications for elderly individuals (and for all of us): comment on “the persistent exclusion of older patients from ongoing clinical trials regarding heart failure”. Arch Intern Med. 2011;171(6):557–8. doi:10.1001/archinternmed.2011.33.

    Article  PubMed  Google Scholar 

  63. Piccolo R, Magnani G, Ariotti S, Gargiulo G, Marino M, Santucci A, et al. Ischemic and bleeding outcomes in elderly patients undergoing a prolonged versus shortened duration of dual antiplatelet therapy after percutaneous coronary intervention. Insights from the PRODIGY randomized trial. EuroIntervention. 2017;12(13). doi:10.4244/EIJ-D-16-00497.

  64. Yeh RW, Kereiakes DJ, Steg PG, Windecker S, Rinaldi MJ, Gershlick AH, et al. Benefits and risks of extended duration dual antiplatelet therapy after PCI in patients with and without acute myocardial infarction. J Am Coll Cardiol. 2015;65(20):2211–21. doi:10.1016/j.jacc.2015.03.003.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Udell JA, Bonaca MP, Collet JP, Lincoff AM, Kereiakes DJ, Costa F, et al. Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials. Eur Heart J. 2016;37(4):390–9. doi:10.1093/eurheartj/ehv443.

    PubMed  Google Scholar 

  66. Costa F, Valgimigli M. Impact of clinical presentation on dual antiplatelet therapy duration: let’s re-evaluate our priorities. J Am Coll Cardiol. 2015;66(10):1203–4. doi:10.1016/j.jacc.2015.05.080.

    Article  PubMed  Google Scholar 

  67. Costa F, Vranckx P, Leonardi S, Moscarella E, Ando G, Calabro P, et al. Impact of clinical presentation on ischaemic and bleeding outcomes in patients receiving 6- or 24-month duration of dual-antiplatelet therapy after stent implantation: a pre-specified analysis from the PRODIGY (Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia) trial. Eur Heart J. 2015;36(20):1242–51. doi:10.1093/eurheartj/ehv038.

    Article  PubMed  Google Scholar 

  68. Giustino G, Chieffo A, Palmerini T, Valgimigli M, Feres F, Abizaid A, et al. Efficacy and safety of dual antiplatelet therapy after complex PCI. J Am Coll Cardiol. 2016;68(17):1851–64. doi:10.1016/j.jacc.2016.07.760.

    Article  CAS  PubMed  Google Scholar 

  69. Adamo M, Costa F, Vranckx P, Leonardi S, Navarese EP, Garcia-Garcia HM, et al. Does smoking habit affect the randomized comparison of 6 versus 24-month dual antiplatelet therapy duration? Insights from the PRODIGY trial. Int J Cardiol. 2015;190:242–5. doi:10.1016/j.ijcard.2015.04.159.

    Article  PubMed  Google Scholar 

  70. Gargiulo G, Costa F, Ariotti S, Biscaglia S, Campo G, Esposito G, et al. Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial. Am Heart J. 2016;174:95–102. doi:10.1016/j.ahj.2016.01.015.

    Article  CAS  PubMed  Google Scholar 

  71. McAllister KS, Ludman PF, Hulme W, de Belder MA, Stables R, Chowdhary S, et al. A contemporary risk model for predicting 30-day mortality following percutaneous coronary intervention in England and Wales. Int J Cardiol. 2016;210:125–32. doi:10.1016/j.ijcard.2016.02.085.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Costa F, Adamo M, Ariotti S, Navarese EP, Biondi-Zoccai G, Valgimigli M. Impact of greater than 12-month dual antiplatelet therapy duration on mortality: Drug-specific or a class-effect? A meta-analysis. Int J Cardiol. 2015;201:179–81. doi:10.1016/j.ijcard.2015.08.058.

    Article  PubMed  Google Scholar 

  73. European Stroke O, Tendera M, Aboyans V, Bartelink ML, Baumgartner I, Clement D, et al. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2011;32(22):2851–906. doi:10.1093/eurheartj/ehr211.

    Article  Google Scholar 

  74. Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017;135(12):e686–725. doi:10.1161/CIR.0000000000000470.

    Article  PubMed  Google Scholar 

  75. Cacoub PP, Bhatt DL, Steg PG, Topol EJ, Creager MA, Investigators C. Patients with peripheral arterial disease in the CHARISMA trial. Eur Heart J. 2009;30(2):192–201. doi:10.1093/eurheartj/ehn534.

    Article  CAS  PubMed  Google Scholar 

  76. Bonaca MP, Bhatt DL, Storey RF, Steg PG, Cohen M, Kuder J, et al. Ticagrelor for prevention of ischemic events after myocardial infarction in patients with peripheral artery disease. J Am Coll Cardiol. 2016;67(23):2719–28. doi:10.1016/j.jacc.2016.03.524.

    Article  CAS  PubMed  Google Scholar 

  77. Franzone A, Piccolo R, Gargiulo G, Ariotti S, Marino M, Santucci A, et al. Prolonged vs short duration of dual antiplatelet therapy after percutaneous coronary intervention in patients with or without peripheral arterial disease: a subgroup analysis of the PRODIGY Randomized Clinical Trial. JAMA Cardiol. 2016;1(7):795–803. doi:10.1001/jamacardio.2016.2811.

    Article  PubMed  Google Scholar 

  78. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS: the Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESCEndorsed by the European Stroke Organisation (ESO). Eur Heart J. 2016. doi:10.1093/eurheartj/ehw210.

    PubMed Central  Google Scholar 

  79. Costa F, Tijssen JG, Ariotti S, Giatti S, Moscarella E, Guastaroba P, et al. Incremental Value of the CRUSADE, ACUITY, and HAS-BLED risk scores for the prediction of hemorrhagic events after coronary stent implantation in patients undergoing long or short duration of dual antiplatelet therapy. J Am Heart Assoc. 2015;4(12):e002524. doi:10.1161/JAHA.115.002524.

    PubMed  PubMed Central  Google Scholar 

  80. Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK, et al. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation. 2009;119(14):1873–82. doi:10.1161/CIRCULATIONAHA.108.828541.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Mehran R, Pocock SJ, Nikolsky E, Clayton T, Dangas GD, Kirtane AJ, et al. A risk score to predict bleeding in patients with acute coronary syndromes. J Am Coll Cardiol. 2010;55(23):2556–66. doi:10.1016/j.jacc.2009.09.076.

    Article  PubMed  Google Scholar 

  82. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093–100. doi:10.1378/chest.10-0134.

    Article  PubMed  Google Scholar 

  83. Yeh RW, Secemsky EA, Kereiakes DJ, Normand SL, Gershlick AH, Cohen DJ, et al. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016;315(16):1735–49. doi:10.1001/jama.2016.3775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Harada Y, Lohaus R, Mayer K, Emmer R, Michel J, Colleran R, et al. Extended validation of a decision tool (DAPT score) in patients randomized to 6 or 12 months dual antiplatelet therapy after percutaneous coronary intervention with predominantly second-generation drug-eluting stents. J Am Coll Cardiol. 2017;68(18):B84–5. doi:10.1016/j.jacc.2016.09.258.

    Article  Google Scholar 

  85. Costa F, van Klaveren D, James S, Heg D, Raber L, Feres F, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet. 2017;389(10073):1025–34. doi:10.1016/S0140-6736(17)30397-5.

    Article  PubMed  Google Scholar 

  86. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–57. doi:10.1056/NEJMoa0904327.

    Article  CAS  PubMed  Google Scholar 

  87. Baber U, Mehran R, Giustino G, Cohen DJ, Henry TD, Sartori S, et al. Coronary thrombosis and major bleeding after PCI with drug-eluting stents: risk scores from PARIS. J Am Coll Cardiol. 2016;67(19):2224–34. doi:10.1016/j.jacc.2016.02.064.

    Article  PubMed  Google Scholar 

  88. Capodanno D, Angiolillo DJ. Tailoring duration of DAPT with risk scores. Lancet. 2017;389(10073):987–9. doi:10.1016/S0140-6736(17)30591-3.

    Article  PubMed  Google Scholar 

  89. Gargiulo G, Windecker S, Vranckx P, Gibson CM, Mehran R, Valgimigli M. A critical appraisal of aspirin in secondary prevention: is less more? Circulation. 2016;134(23):1881–906. doi:10.1161/CIRCULATIONAHA.116.023952.

    Article  CAS  PubMed  Google Scholar 

  90. Rollini F, Franchi F, Angiolillo DJ. Switching P2Y12-receptor inhibitors in patients with coronary artery disease. Nat Rev Cardiol. 2016;13(1):11–27. doi:10.1038/nrcardio.2015.113.

    Article  CAS  PubMed  Google Scholar 

  91. Capodanno D, Angiolillo DJ. Antiplatelet therapy after implantation of bioresorbable vascular scaffolds: a review of the published data, practical recommendations, and future directions. JACC Cardiovasc Interv. 2017;10(5):425–37. doi:10.1016/j.jcin.2016.12.279.

    Article  PubMed  Google Scholar 

  92. Serruys PW, Chevalier B, Sotomi Y, Cequier A, Carrie D, Piek JJ, et al. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet. 2016;388(10059):2479–91. doi:10.1016/S0140-6736(16)32050-5.

    Article  CAS  PubMed  Google Scholar 

  93. Wykrzykowska JJ, Kraak RP, Hofma SH, van der Schaaf RJ, Arkenbout EK, IJsselmuiden IJ, et al. Bioresorbable scaffolds versus metallic stents in routine PCI. N Engl J Med. 2017. doi:10.1056/NEJMoa1614954.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Policlinic “G. Martino”, University of Messina, Messina, Italy

    Francesco Costa

  2. Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands

    Francesco Costa & Marco Valgimigli

  3. Swiss Cardiovascular Center Bern, Bern University Hospital, 3010, Bern, Switzerland

    Stephan Windecker & Marco Valgimigli

Authors
  1. Francesco Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephan Windecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marco Valgimigli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marco Valgimigli.

Ethics declarations

Funding

No external funds were used in the preparation of this manuscript.

Conflict of interest

Francesco Costa declares no conflicts of interest that might be relevant to the contents of this manuscript. Stephan Windecker reports receiving grants from Abbott, Biotronik, Biosensors, Edwards Lifesciences, Medtronic, and St Jude Medical; personal fees from AstraZeneca and Daiichi Sankyo; and grants and personal fees from Boston Scientific and Sanofi, unrelated to this work. Marco Valgimigli has received research grants from The Medicines Company, Terumo, and AstraZeneca, unrelated to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Costa, F., Windecker, S. & Valgimigli, M. Dual Antiplatelet Therapy Duration: Reconciling the Inconsistencies. Drugs 77, 1733–1754 (2017). https://doi.org/10.1007/s40265-017-0806-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-017-0806-1

Search

Navigation