Current Cardiology Reports

, 20:110 | Cite as

Management of Anticoagulation in Patients with Atrial Fibrillation Undergoing PCI: Double or Triple Therapy?

  • Benjamin E. Peterson
  • Deepak L. BhattEmail author
Invasive Electrophysiology and Pacing (EK Heist, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Invasive Electrophysiology and Pacing


Purpose of Review

This review aims to discuss the use of antithrombotic therapy in patients with atrial fibrillation who undergo coronary stenting with emphasis on the use of double vs triple therapy.

Recent Findings

When combined with systemic anticoagulation, dual antiplatelet therapy results in an unacceptable increase in bleeding without any improvement in prevention of thrombotic events. Direct oral anticoagulants combined with single antiplatelet therapy have reduced bleeding compared with warfarin plus dual antiplatelet therapy. Triple anticoagulation therapy with warfarin or direct oral anticoagulants leads to an excess of bleeding and is not superior in preventing thrombotic events.


Recent randomized, controlled trials have shown a significant reduction in major bleeding events in patients treated with dual antithrombotic therapy compared with triple therapy without any difference in efficacy. These findings call into question whether triple therapy should remain a part of standard practice.


Atrial fibrillation Percutaneous coronary intervention Antiplatelet therapy Anticoagulation 


Compliance with Ethical Standards

Conflict of Interest

Dr. Benjamin E. Peterson declares that he has no conflict of interest.

Dr. Deepak L. Bhatt discloses the following relationships:

Advisory Board: Cardax, Elsevier (Practice Update Cardiology), Medscape Cardiology, Regado Biosciences. Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft.

Chair: American Heart Association Quality Oversight Committee. Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute.

Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News,; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees).

Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair).

Research Funding: Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company.

Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, PLx Pharma, Takeda.

Human and Animal Rights and Informed Consent

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


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. Heart disease and stroke Statistics-2018 update: a report from the American Heart Association. Circulation. 2018;137(12):e67–492.CrossRefGoogle Scholar
  2. 2.
    Kralev S, Schneider K, Lang S, Süselbeck T, Borggrefe M. Incidence and severity of coronary artery disease in patients with atrial fibrillation undergoing first-time coronary angiography. PLoS One. 2011;6(9):e24964.CrossRefGoogle Scholar
  3. 3.
    Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, et al. Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation. 2014;129(8):837–47.CrossRefGoogle Scholar
  4. 4.
    ACTIVE Writing Group of the ACTIVE Investigators, Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the atrial fibrillation Clopidogrel trial with Irbesartan for prevention of vascular events (ACTIVE W): a randomised controlled trial. Lancet. 2006;367(9526):1903–12.CrossRefGoogle Scholar
  5. 5.
    Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146(12):857–67.CrossRefGoogle Scholar
  6. 6.
    Goto S, Bhatt DL, Röther J, Alberts M, Hill MD, Ikeda Y, et al. Prevalence, clinical profile, and cardiovascular outcomes of atrial fibrillation patients with atherothrombosis. Am Heart J. 2008;156(5):855–63. 863.e2CrossRefGoogle Scholar
  7. 7.
    Ruff CT, Bhatt DL, Steg PG, Gersh BJ, Alberts MJ, Hoffman EB, et al. Long-term cardiovascular outcomes in patients with atrial fibrillation and atherothrombosis in the REACH registry. Int J Cardiol. 2014;170(3):413–8.CrossRefGoogle Scholar
  8. 8.
    Lip GY, Gibbs CR. Antiplatelet agents versus control or anticoagulation for heart failure in sinus rhythm. Cochrane Database Syst Rev. 2001;4:CD003333.Google Scholar
  9. 9.
    Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet. 1994 Mar 19;343(8899):687–91.Google Scholar
  10. 10.
    • Dewilde WJM, Oirbans T, Verheugt FWA, Kelder JC, De Smet BJGL, Herrman J-P, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381(9872):1107–15. This study showed improved safety and efficacy for warfarin plus clopidogrel over traditional triple therapy in patients with atrial fibrillation who had undergone PCI CrossRefGoogle Scholar
  11. 11.
    • Fiedler KA, Maeng M, Mehilli J, Schulz-Schüpke S, Byrne RA, Sibbing D, et al. Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: The ISAR-TRIPLE Trial. J Am Coll Cardiol, In this study, six weeks of triple therapy was not different from six months of triple therapy in terms of efficacy or safety. 2015;65(16):1619–29.Google Scholar
  12. 12.
    • Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med. 2016;375(25):2423–34. In this study, two different combinations of low-dose rivaroxaban and antiplatelet therapy were superior to traditional triple therapy in preventing bleeding, without any loss of efficacy CrossRefGoogle Scholar
  13. 13.
    • Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med. 2017;377(16):1513–24. In this study, patients randomized to dabigatran plus P2Y12 inhibitors had less bleeding and no worse efficacy than traditional triple therapy CrossRefGoogle Scholar
  14. 14.
    January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):2071–104.CrossRefGoogle Scholar
  15. 15.
    Angiolillo DJ, Goodman SG, Bhatt DL, Eikelboom JW, Price MJ, Moliterno DJ, et al. Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A North American Perspective-2016 Update. Circ Cardiovasc Interv. 2016;9(11).Google Scholar
  16. 16.
    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. Eur J Cardiothorac Surg. 2016 Nov;50(5):e1–88.CrossRefGoogle Scholar
  17. 17.
    Depta JP, Cannon CP, Fonarow GC, Zhao X, Peacock WF, Bhatt DL, et al. Patient characteristics associated with the choice of triple antithrombotic therapy in acute coronary syndromes. Am J Cardiol. 2009;104(9):1171–8.CrossRefGoogle Scholar
  18. 18.
    Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation. 2007;115(21):2689–96.CrossRefGoogle Scholar
  19. 19.
    Vinereanu D, Stevens SR, Alexander JH, Al-Khatib SM, Avezum A, Bahit MC, et al. Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial. Eur Heart J. 2015;36(46):3268–75.PubMedGoogle Scholar
  20. 20.
    Chhatriwalla AK, Amin AP, Kennedy KF, House JA, Cohen DJ, Rao SV, et al. Association between bleeding events and in-hospital mortality after percutaneous coronary intervention. JAMA. 2013;309(10):1022–9.CrossRefGoogle Scholar
  21. 21.
    Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the bleeding academic research consortium. Circulation. 2011;123(23):2736–47.CrossRefGoogle Scholar
  22. 22.
    O’Brien EC, Holmes DN, Thomas LE, Fonarow GC, Allen LA, Gersh BJ, et al. Prognostic Significance of Nuisance Bleeding in Anticoagulated Patients with Atrial Fibrillation. Circulation. 2018Google Scholar
  23. 23.
    Depta JP, Bhatt DL. Atherothrombosis and atrial fibrillation: important and often overlapping clinical syndromes. Thromb Haemost. 2010;104(4):657–63.CrossRefGoogle Scholar
  24. 24.
    Sherwood MW, Lopes RD, Sun JL, Liaw D, Harrington RA, Wallentin L, et al. Apixaban following acute coronary syndromes in patients with prior stroke: insights from the APPRAISE-2 trial. Am Heart J. 2018;197:1–8.CrossRefGoogle Scholar
  25. 25.
    Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.CrossRefGoogle Scholar
  26. 26.
    Bavry AA, Bhatt DL. Appropriate use of drug-eluting stents: balancing the reduction in restenosis with the concern of late thrombosis. Lancet. 2008;371(9630):2134–43.CrossRefGoogle Scholar
  27. 27.
    Connolly SJ, Eikelboom J, Joyner C, Diener H-C, Hart R, Golitsyn S, et al. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806–17.CrossRefGoogle Scholar
  28. 28.
    CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348(9038):1329–39.CrossRefGoogle Scholar
  29. 29.
    Bhatt DL, Hirsch AT, Ringleb PA, Hacke W, Topol EJ. Reduction in the need for hospitalization for recurrent ischemic events and bleeding with clopidogrel instead of aspirin. CAPRIE investigators. Am Heart J. 2000;140(1):67–73.CrossRefGoogle Scholar
  30. 30.
    Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51.CrossRefGoogle Scholar
  31. 31.
    Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.CrossRefGoogle Scholar
  32. 32.
    Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104.CrossRefGoogle Scholar
  33. 33.
    Hohnloser SH, Hijazi Z, Thomas L, Alexander JH, Amerena J, Hanna M, et al. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J. 2012;33(22):2821–30.CrossRefGoogle Scholar
  34. 34.
    Hylek EM, Held C, Alexander JH, Lopes RD, De Caterina R, Wojdyla DM, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: the ARISTOTLE trial (Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation): predictors, characteristics, and clinical outcomes. J Am Coll Cardiol. 2014;63(20):2141–7.CrossRefGoogle Scholar
  35. 35.
    Hess CN, Al-Khatib SM, Granger CB, Lopes R. A review of apixaban for stroke prevention in atrial fibrillation: insights from ARISTOTLE. Expert Rev Cardiovasc Ther. 2013;11(9):1105–14.CrossRefGoogle Scholar
  36. 36.
    Connolly SJ, Milling TJ, Eikelboom JW, Gibson CM, Curnutte JT, Gold A, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med. 2016;375(12):1131–41.CrossRefGoogle Scholar
  37. 37.
    Ruff CT, Giugliano RP, Antman EM. Management of Bleeding with non-Vitamin K Antagonist Oral Anticoagulants in the era of specific reversal agents. Circulation. 2016;134(3):248–61.CrossRefGoogle Scholar
  38. 38.
    Peterson BE, Al-Khatib SM, Granger CB. Apixaban to prevent stroke in patients with atrial fibrillation: a review. Ther Adv Cardiovasc Dis. 2017;11(3):91–104.CrossRefGoogle Scholar
  39. 39.
    Halvorsen S, Atar D, Yang H, De Caterina R, Erol C, Garcia D, et al. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial. Eur Heart J. 2014;35(28):1864–72.CrossRefGoogle Scholar
  40. 40.
    Hess CN, Broderick S, Piccini JP, Alexander KP, Newby LK, Shaw LK, et al. Antithrombotic therapy for atrial fibrillation and coronary artery disease in older patients. Am Heart J. 2012;164(4):607–15.CrossRefGoogle Scholar
  41. 41.
    Qamar A, Bhatt DL. Anticoagulation therapy: balancing the risks of stroke and bleeding in CKD. Nat Rev Nephrol. 2015;11(4):200–2.CrossRefGoogle Scholar
  42. 42.
    Qamar A, Bhatt DL. Stroke prevention in atrial fibrillation in patients with chronic kidney disease. Circulation. 2016;133(15):1512–5.CrossRefGoogle Scholar
  43. 43.
    Lip GYH, Connolly S, Yusuf S, Shestakovska O, Flaker G, Hart R, et al. Modification of outcomes with aspirin or apixaban in relation to CHADS(2) and CHA(2)DS(2)-VASc scores in patients with atrial fibrillation: a secondary analysis of the AVERROES study. Circ Arrhythm Electrophysiol. 2013;6(1):31–8.CrossRefGoogle Scholar
  44. 44.
    Olesen JB, Lip GYH, Kamper A-L, Hommel K, Køber L, Lane DA, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med. 2012;367(7):625–35.CrossRefGoogle Scholar
  45. 45.
    Avezum A, Lopes RD, Schulte PJ, Lanas F, Gersh BJ, Hanna M, et al. Apixaban in comparison with warfarin in patients with atrial fibrillation and Valvular heart disease: findings from the Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation (ARISTOTLE) trial. Circulation. 2015;132(8):624–32.CrossRefGoogle Scholar
  46. 46.
    Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369(13):1206–14.CrossRefGoogle Scholar
  47. 47.
    Mega JL, Braunwald E, Mohanavelu S, Burton P, Poulter R, Misselwitz F, et al. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet. 2009;374(9683):29–38.CrossRefGoogle Scholar
  48. 48.
    Mega JL, Braunwald E, Wiviott SD, Bassand J-P, Bhatt DL, Bode C, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366(1):9–19.CrossRefGoogle Scholar
  49. 49.
    Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011;365(8):699–708.CrossRefGoogle Scholar
  50. 50.
    Hess CN, James S, Lopes RD, Wojdyla DM, Neely ML, Liaw D, et al. Apixaban plus mono versus dual antiplatelet therapy in acute coronary syndromes: insights from the APPRAISE-2 trial. J Am Coll Cardiol. 2015;66(7):777–87.CrossRefGoogle Scholar
  51. 51.
    Oldgren J, Wallentin L, Alexander JH, James S, Jönelid B, Steg G, et al. New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis. Eur Heart J. 2013;34(22):1670–80.CrossRefGoogle Scholar
  52. 52.
    Pareek M, Bhatt DL, Ten Berg JM, Kristensen SD, Grove EL. Antithrombotic strategies for preventing long-term major adverse cardiovascular events in patients with non-valvular atrial fibrillation who undergo percutaneous coronary intervention. Expert Opin Pharmacother. 2017;18(9):875–83.CrossRefGoogle Scholar
  53. 53.
    Gibson CM, Mehran R, Bode C, Halperin J, Verheugt F, Wildgoose P, et al. An open-label, randomized, controlled, multicenter study exploring two treatment strategies of rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention (PIONEER AF-PCI). Am Heart J. 2015;169(4):472–478.e5.CrossRefGoogle Scholar
  54. 54.
    Gibson CM, Pinto DS, Chi G, Arbetter D, Yee M, Mehran R, et al. Recurrent hospitalization among patients with atrial fibrillation undergoing intracoronary stenting treated with 2 treatment strategies of rivaroxaban or a dose-adjusted Oral vitamin K antagonist treatment strategy. Circulation. 2017;135(4):323–33.CrossRefGoogle Scholar
  55. 55.
    Bhatt DL. O PIONEERs! The beginning of the end of full-dose triple therapy with warfarin? Circulation. 2017;135(4):334–7.CrossRefGoogle Scholar
  56. 56.
    Cannon CP, Gropper S, Bhatt DL, Ellis SG, Kimura T, Lip GYH, et al. Design and rationale of the RE-DUAL PCI trial: a prospective, randomized, phase 3b study comparing the safety and efficacy of dual antithrombotic therapy with dabigatran Etexilate versus warfarin triple therapy in patients with Nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stenting. Clin Cardiol. 2016;39(10):555–64.CrossRefGoogle Scholar
  57. 57.
    • Golwala HB, Cannon CP, Steg PG, Doros G, Qamar A, Ellis SG, et al. Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials. Eur Heart J. 2018;39(19):1726–1735a. This analysis found consistently lower bleeding, but did not detect a difference in trial-defined MACE events or individual outcomes of death, cardiovascular death, myocardial infarction, stent thrombosis, or stroke between patients taking oral anticoagulants plus single antiplatelet therapy vs double therapy CrossRefGoogle Scholar
  58. 58.
    Vranckx P, Lewalter T, Valgimigli M, Tijssen JG, Reimitz P-E, Eckardt L, et al. Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: rationale and design of the ENTRUST-AF PCI trial. Am Heart J. 2018;196:105–12.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Brigham and Women’s Hospital Heart and Vascular CenterHarvard Medical SchoolBostonUSA

Personalised recommendations