Skip to main content
Log in

Combining oral anticoagulation and antiplatelet therapies: appropriate patient selection

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Anticoagulant therapy and antiplatelet therapy are used regularly for prevention of arterial and venous thrombosis, and combinations of the two drug classes are seen with relative frequency in clinical practice. While co-prescribing is as high as 39–55% in some real-world cohort studies, the number of patients that meet criteria for combination therapy based on the overall body of evidence is likely much lower. This may not always be realized by prescribers, and many patients may be continued on long term combination therapies that provide little additional benefit, and carry significant risk for harm. Given the heightened bleeding risk with combination therapies, prescribers should readily reassess the risk: benefit ratio in all patients on combination therapies. Combined antiplatelet and anticoagulant therapy should be used only in those with a low risk of bleeding who have a higher risk of thromboembolic disease events. Most patients with coronary artery disease, atrial fibrillation, peripheral arterial disease, or bioprosthetic cardiac valves will not benefit from combining antiplatelet and anticoagulant therapies. Conversely, patient populations more likely to derive benefit from antiplatelet-anticoagulant combinations include those with mechanical cardiac valves, patients undergoing percutaneous cardiac intervention who have another indication for anticoagulant therapy, and patients with recurrent thrombotic events while being treated with a single agent. This article will attempt to provide readers with a framework to assess which patient populations are likely to derive the greatest benefit with combination anticoagulant-antiplatelet therapies relative to the weighted risk for bleeding.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hira RS, Kennedy K, Nambi V et al (2015) Frequency and practice-level variation in inappropriate aspirin use for the primary prevention of cardiovascular disease: insights from the National Cardiovascular Disease Registry’s Practice Innovation and Clinical Excellence registry. J Am Coll Cardiol 65(2):111–121

    Article  PubMed  Google Scholar 

  2. Barnes GD, Lucas E, Alexander GC, Goldberger ZD (2015) National trends in ambulatory oral anticoagulant use. Am J Med 128(12):1300-5.e2

    Article  PubMed  Google Scholar 

  3. Mackman N (2008) Triggers, targets and treatments for thrombosis. Nature 451(7181):914–918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. De Caterina R, Ammentorp B, Darius H et al (2014) Frequent and possibly inappropriate use of combination therapy with an oral anticoagulant and antiplatelet agents in patients with atrial fibrillation in Europe. Heart 100:1625–1635

    Article  PubMed  Google Scholar 

  5. Bauersachs R, Berkowitz SD, Brenner B et al (2010) Rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363(26):2499–2510

    Article  CAS  PubMed  Google Scholar 

  6. Büller HR, Prins MH, Lensin AW et al (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366(14):1287–1297

    Article  PubMed  Google Scholar 

  7. Agnelli A, Buller HR, Cohen A et al (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369(9):799–808

    Article  CAS  PubMed  Google Scholar 

  8. Connolly SJ, EZekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361(12):1139–1151

    Article  CAS  PubMed  Google Scholar 

  9. Patel MR, Mahaffery KW, Garg J et al (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891

    Article  CAS  PubMed  Google Scholar 

  10. Granger CB, Alexander JH, McMurray JJV et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992

    Article  CAS  PubMed  Google Scholar 

  11. Barra ME, Fanikos J, Connors JM et al (2016) Evaluation of dose-reduced direct oral anticoagulant therapy. Am J Med 129(11):1198–1204

    Article  CAS  PubMed  Google Scholar 

  12. Johnson SG, Rogers K, Delate T, Witt DM (2008) Outcomes associated with combined antiplatelet and anticoagulant therapy. Chest 133(4):948–954

    Article  CAS  PubMed  Google Scholar 

  13. Steinberg BA, Kim S, Piccini JP et al (2013) Use and associated risks of concomitant aspirin therapy with oral anticoagulation in patients with atrial fibrillation: insights from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry. Circulation 128(7):721–728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. So CH, Eckman MH (2017) Combined aspirin and anticoagulant therapy in patients with atrial fibrillation. J Thromb Thrombolysis 43(1):7–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dentali F, Douketis JD, Lim W, Crowther M (2007) Combined aspirin-oral anticoagulant therapy compared with oral anticoagulant therapy alone among patients at risk for cardiovascular disease: a meta-analysis of randomized trials. Arch Intern Med 167(2):117–124

    Article  CAS  PubMed  Google Scholar 

  16. Sorensen R, Hansen ML, Abildstrom SZ et al (2009) Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet 374(9706):1967–1974

    Article  CAS  PubMed  Google Scholar 

  17. Camm AJ, Kirchhof P, Lip GY et al (2010) Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 31(19):2369–2429

    Article  PubMed  Google Scholar 

  18. Mohr JP, Thompson JLP, Lazar RM et al (2001) A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 345(20):1444–1451

    Article  CAS  PubMed  Google Scholar 

  19. Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H (2002) Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 347(13):969–974

    Article  CAS  PubMed  Google Scholar 

  20. Anand S, Yusuf S, Xie C et al (2007) Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med 357(3):217–227

    Article  CAS  PubMed  Google Scholar 

  21. Ruff CT, Giugliano RP, Braunwald E et al (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383(9921):955–962

    Article  CAS  PubMed  Google Scholar 

  22. Artang R, Rome E, Nielsen JD, Vidaillet HF (2013) Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors. Am J Cardiol 112(12):1973–1979

    Article  CAS  PubMed  Google Scholar 

  23. Witt DM, Clark NP, Kaatz S, Schnurr T, Ansell JE (2016) Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism. J Thromb Thrombolysis 41:187–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kearon C, Akl EA, Ornelas J et al (2016) Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest (149(2):315–352

    Article  PubMed  Google Scholar 

  25. Alexander JH, Lopes RD, Thomas L et al (2014) Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J 35(4):224–232

    Article  CAS  PubMed  Google Scholar 

  26. Shah R, Hellkamp A, Lokhnygina Y et al (2016) Use of concomitant aspirin in patients with atrial fibrillation: findings from the ROCKET AF trial. Am Heart J 179:77–86

    Article  CAS  PubMed  Google Scholar 

  27. Oldgren J, Wallentin L, Alexander JH et al (2013) 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 34(22):1670–1680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Xu H, Ruff CT, Giugliano RP et al (2016) Concomitant use of single antiplatelet therapy with edoxaban or warfarin in patients with atrial fibrillation: analysis from the ENGAGE AF-TIMI48 Trial. J Am Heart Assoc. https://doi.org/10.1161/JAHA.115.002587

    Google Scholar 

  29. Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH. (2012) Antithrombotic and thrombolytic therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl):e576S–e600S

    Google Scholar 

  30. Colli A, Mestres CA, Castella M, Gherli T (2007) Comparing warfarin to aspirin (WoA) after aortic valve replacement with the St. Jude Medical Epic heart valve bioprosthesis: results of the WoA Epic pilot trial. J Heart Valve Dis 16(6):667–671

    PubMed  Google Scholar 

  31. Aramendi JI, Mestres CA, Martinez-Leon J et al (2005) Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement: prospective, randomized, co-operative trial. Eur J Cardiotherac Surg 27(5):854–860

    Article  Google Scholar 

  32. Heras M, Chesebro JH, Fuster V et al (1995) High risk of thrombemboli early after bioprosthetic cardiac valve replacement. J Am Coll Cardiol 25(5):1111–1119

    Article  CAS  PubMed  Google Scholar 

  33. Baigent C, Sudlow C, Collins R (2002) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 324(7329):71–86

    Article  Google Scholar 

  34. Alonso-Coello P, Bellmunt S, McGorrian C et al. (2012) Antithrombotic therapy in peripheral artery disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl):e669S–e690s

    Google Scholar 

  35. Johnson WC, Williford WO, Corson JD, Padberg FT Jr (2004) Hemorrhagic complications during long-term postoperative warfarin administration in patients undergoing lower extremity arterial bypass surgery. Vascular 12(6):362–368

    Article  PubMed  Google Scholar 

  36. Camm AJ, Lip GY, De Caterina R et al (2012) 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 33(21):2719–2747

    Article  PubMed  Google Scholar 

  37. van Es RF, Jonker JJ, Verheugt FW et al (2002) Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 360(9327):109–113

    Article  PubMed  Google Scholar 

  38. Andreotti F, Testa L, Biondi-Zoccai CG, Crea F (2006) Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J 27(5):519–526

    Article  CAS  PubMed  Google Scholar 

  39. Testa L, Zoccai GB, Porto I et al (2007) Adjusted indirect meta-analysis of aspirin plus warfarin at international normalized ratios 2 to 3 versus aspirin plus clopidogrel after acute coronary syndromes. Am J Cardiol 99(12):1637–1642

    Article  CAS  PubMed  Google Scholar 

  40. Carreras ET, Mega JL (2013) Balancing antiplatelet and anticoagulant therapies in patients with cardiovascular disease. Cardiol Ther 2(1):85–96

    Article  PubMed  PubMed Central  Google Scholar 

  41. Eikelboom JW, Connolly SJ, Bosch J et al (2017) Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 377(14):1319–1330

    Article  CAS  PubMed  Google Scholar 

  42. Valgimigli M, Beuno H, Byrne RA et al (2017) 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. https://doi.org/10.1093/eurheartj/ehx419.

    Google Scholar 

  43. Dewilde WJ, Oirbans T, Verheugt FW et al (2013) 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 381(9872):1107–1115

    Article  CAS  PubMed  Google Scholar 

  44. Gibson CM, Mehran R, Bode C et al (2016) Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med 375(25):2423–2434

    Article  CAS  PubMed  Google Scholar 

  45. Cannon CP, Bhatt DL, Oldgren J et al (2017) Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med 377(16):1513–1524

    Article  CAS  PubMed  Google Scholar 

  46. January CT, Wann LS, Alpert JS et al (2014) 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 130(23):e199–e267

    Article  Google Scholar 

  47. Gibson CM, Pinto DS, Chi G et al (2017) 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 135(4):323–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Levine GN, Bates ER, Bittl JA et al (2016) 2016 ACC/AHA Guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. J Am Coll Cardiol 68(10):1116–1139

    Article  Google Scholar 

  49. Conway SE, Hwang AY, Ponte CD, Gums JG (2017) Laboratory and clinical monitoring of direct acting oral anticoagulants: what clinicians need to know. Pharmacotherapy 37(2):236–248

    Article  PubMed  Google Scholar 

  50. Donadini MP, Douketis JD (2010) Combine warfarin-aspirin therapy: what is the evidence? J Thromb Thrombolysis 29(2):208–213

    Article  CAS  PubMed  Google Scholar 

  51. Kernan WN, Ovbiagele B, Black HR et al (2014) Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45:2160–2236

    Article  PubMed  Google Scholar 

Download references

Funding

This study was not subject to any funding.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jeremy W. Vandiver.

Ethics declarations

Conflict of interest

Neither Dr. Vandiver or Dr. Beavers have any conflicts of interest to report.

Ethical approval

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

Informed consent

Not applicable.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vandiver, J.W., Diane Beavers, K. Combining oral anticoagulation and antiplatelet therapies: appropriate patient selection. J Thromb Thrombolysis 45, 423–431 (2018). https://doi.org/10.1007/s11239-018-1635-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-018-1635-0

Keywords

Navigation