Skip to main content
SpringerLink
Log in

Antithrombotic Therapy in Peripheral Artery Disease: Stepping in the Right Direction

  • Review Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

We reviewed the various antithrombotic therapies available to treat peripheral artery disease (PAD). A literature review using the PubMed and MEDLINE databases used the following keywords: antithrombotic therapy, anticoagulation, peripheral artery disease, and peripheral vascular disease. Randomized studies written in English that assessed the use of antithrombotic therapy in patients with PAD were evaluated. PAD is a worldwide condition that limits blood flow in the lower extremities, leading to a risk of major adverse cardiovascular events and major adverse limb events. Antithrombotic therapy is necessary to prevent these complications, and the choice of therapy depends upon the stage of disease progression. For symptomatic patients in the beginning stage, single antiplatelet therapy (SAPT) is the preferred therapy, specifically, aspirin. For patients undergoing endovascular revascularization, the preferred therapy is dual antiplatelet therapy using aspirin and clopidogrel combined for at least the first month followed by long-term SAPT. For patients undergoing surgical revascularization, the preferred choice of therapy depends upon the type of graft used, with better results obtained with antiplatelet therapy for prosthetic grafts and anticoagulation for venous grafts. New studies have shown that therapy using both antiplatelets and anticoagulation in the form of aspirin plus low-dose rivaroxaban can reduce complications in all three patient populations, which has paved the way for future studies featuring direct oral anticoagulants with the potential to change current guideline recommendations.

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

Similar content being viewed by others

References

  1. Krishna S, Moxon J, Golledge J. A review of the pathophysiology and potential biomarkers for peripheral artery disease. Int J Mol Sci. 2015;16(12):11294–322. https://doi.org/10.3390/ijms160511294.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Foley TR, Waldo SW, Armstrong EJ. Antithrombotic therapy in peripheral artery disease. Vasc Med. 2016;21(2):156–69. https://doi.org/10.1177/1358863x15622987.

    Article  PubMed  CAS  Google Scholar 

  3. Zemaitis MR, Boll JM, Dreyer MA. Peripheral arterial disease. [Updated 2020 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430745/

  4. Creager MA, Loscalzo J. Vascular diseases of the extremities. In: Fauci AS, Longo DL, Kasper D, Braunwald E, Jameson JL, Loscalzo J, Hauser SL, editors. Harrison’s principles of internal medicine. 17th ed. Columbus: McGraw Hill; 2008. p. 454–66.

    Google Scholar 

  5. Rooke TW, Wennberg PW. Diagnosis and management of diseases of the peripheral arteries and veins. In: Fuster V, O’Rourke RA, Walsh RA, Poole-Wilson P, eds. Hurst’s The Heart. 12th ed. New York: McGraw-Hill; 2007.

  6. Mcdermott MM, Criqui MH, Greenland P, et al. Leg strength in peripheral arterial disease: associations with disease severity and lower-extremity performance. J Vasc Surg. 2004;39(3):523–30. https://doi.org/10.1016/j.jvs.2003.08.038.

    Article  PubMed  Google Scholar 

  7. Hussain MA, Al-Omran M, Creager MA, et al. Antithrombotic therapy for peripheral artery disease. J Am Coll Cardiol. 2018;71(21):2450–67. https://doi.org/10.1016/j.jacc.2018.03.483.

    Article  PubMed  Google Scholar 

  8. Hardman R, Jazaeri O, Yi J, et al. Overview of classification systems in peripheral artery disease. Semin Interv Radiol. 2014;31(04):378–88. https://doi.org/10.1055/s-0034-1393976.

    Article  Google Scholar 

  9. Varu VN, Hogg ME, Kibbe MR. Critical limb ischemia. J Vasc Surg. 2010;51(1):230–41. https://doi.org/10.1016/j.jvs.2009.08.073.

    Article  PubMed  Google Scholar 

  10. Cassar K. Intermittent claudication. BMJ. 2006;333(7576):1002–5. https://doi.org/10.1136/bmj.39001.562813.de.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kruidenier LM, Nicolai SP, Willigendael EM, et al. Functional claudication distance: a reliable and valid measurement to assess functional limitation in patients with intermittent claudication. BMC Cardiovasc Disord. 2009. https://doi.org/10.1186/1471-2261-9-9.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Olinic D-M, Stanek A, Tătaru D-A, et al. Acute limb ischemia: an update on diagnosis and management. J Clin Med. 2019;8(8):1215. https://doi.org/10.3390/jcm8081215.

    Article  PubMed Central  Google Scholar 

  13. McDermott MM. Role of the ankle brachial index. In: Kramer C, editor. Imaging in peripheral arterial disease. Cham: Springer; 2020. https://doi.org/10.1007/978-3-030-24596-2_2.

  14. Høyer C, Sandermann J, Petersen LJ. The toe-brachial index in the diagnosis of peripheral arterial disease. J Vasc Surg. 2013;58(1):231–8. https://doi.org/10.1016/j.jvs.2013.03.044.

    Article  PubMed  Google Scholar 

  15. QuantaFlo. Semler Scientific. 2018. http://www.semlerscientific.com/quantaflo/. Accessed 28 July 2020.

  16. Jones WS, Patel MR. Antithrombotic therapy in peripheral artery disease. J Am Coll Cardiol. 2018;71(3):352–62. https://doi.org/10.1016/j.jacc.2017.11.021.

    Article  PubMed  Google Scholar 

  17. Kinlay S. Management of critical limb ischemia. Circ Cardiovasc Interv. 2016. https://doi.org/10.1161/circinterventions.115.001946.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Iqbal AM, Lopez RA, Hai O. Antiplatelet medications. [Updated 2020 May 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537062/.

  19. Wijeyeratne YD, Heptinstall S. Anti-platelet therapy: ADP receptor antagonists. Br J Clin Pharmacol. 2011;72(4):647–57. https://doi.org/10.1111/j.1365-2125.2011.03999.x.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Angiolillo DJ, Goodman SG, Bhatt DL, et al. Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention. Circulation. 2018;138:527–36. https://doi.org/10.1161/CIRCULATIONAHA.

    Article  PubMed  CAS  Google Scholar 

  21. Harter K, Levine M, Henderson S. Anticoagulation drug therapy: a review. West J Emerg Med. 2015;16(1):11–7. https://doi.org/10.5811/westjem.2014.12.22933.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Warfarin and calciphylaxis—a rare but serious adverse event. MedSafe New Zealand Medicines and Medical Devices Safety Authority. 2017. https://www.medsafe.govt.nz/profs/PUArticles/September2017/WarfarinAndCalciphylaxis.htm#References. Accessed 7 Dec 2020.

  23. Narula N, Dannenberg AJ, Olin JW, et al. Pathology of peripheral artery disease in patients with critical limb ischemia. J Am Coll Cardiol. 2018;72(18):2152–63. https://doi.org/10.1016/j.jacc.2018.08.002.

    Article  PubMed  CAS  Google Scholar 

  24. Conte MS, Pomposelli FB, Clair DG, et al. Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: Management of asymptomatic disease and claudication. J Vasc Surg. 2015. https://doi.org/10.1016/j.jvs.2014.12.009.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: executive summary. J Am Coll Cardiol. 2017;69(11):1465–508. https://doi.org/10.1016/j.jacc.2016.11.008.

    Article  PubMed  Google Scholar 

  26. Aboyans V, Ricco JB, Bartelink MLE, et al. ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Endorsed by the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763–816. https://doi.org/10.1093/eurheartj/ehx095.

    Article  PubMed  Google Scholar 

  27. Critical Leg Ischaemia Prevention Study (CLIPS) Group. Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial. J Intern Med. 2007;261(3):276–84. https://doi.org/10.1111/j.1365-2796.2006.01763.x.

  28. Cacoub PP, Bhatt DL, Steg P, et al. Patients with peripheral arterial disease in the CHARISMA trial. Eur Heart J. 2008;30(2):192–201. https://doi.org/10.1093/eurheartj/ehn534.

    Article  CAS  Google Scholar 

  29. Hiatt WR, Fowkes FG, Heizer G, et al. Ticagrelor versus clopidogrel in symptomatic peripheral artery disease. J Vasc Surg. 2017;65(4):1238. https://doi.org/10.1016/j.jvs.2017.02.011.

    Article  Google Scholar 

  30. The Warfarin Antiplatelet Vascular Evaluation Trial Investigators. Oral anticoagulant and antiplatelet therapy in peripheral arterial disease. J Vasc Surg. 2007;46(6):1306. https://doi.org/10.1016/j.jvs.2007.10.022.

    Article  Google Scholar 

  31. Anand SS, Caron F, Eikelboom JW, et al. Major adverse limb events and mortality in patients with peripheral artery disease. J Am Coll Cardiol. 2018;71(20):2306–15. https://doi.org/10.1016/j.jacc.2018.03.008.

    Article  PubMed  Google Scholar 

  32. Wiseman JT, Fernandes-Taylor S, Saha S, et al. Endovascular versus open revascularization for peripheral arterial disease. Ann Surg. 2017;265(2):424–30. https://doi.org/10.1097/sla.0000000000001676.

    Article  PubMed  Google Scholar 

  33. Shammas NW. Epidemiology, classification, and modifiable risk factors of peripheral arterial disease. Vasc Health Risk Manag. 2007;3(2):229–34. https://doi.org/10.2147/vhrm.2007.3.2.229.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Park K-M, Kim YW, Yang S-S, et al. Comparisons between prosthetic vascular graft and saphenous vein graft in femoro-popliteal bypass. Ann Surg Treat Res. 2014;87(1):35. https://doi.org/10.4174/astr.2014.87.1.35.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Roll S, Muller-Nordhorn J, Keil T, et al. Dacron® vs. PTFE as bypass materials in peripheral vascular surgery—systematic review and meta-analysis. BMC Surg. 2008. https://doi.org/10.1186/1471-2482-8-22.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tepe G, Bantleon R, Brechtel K, et al. Management of peripheral arterial interventions with mono or dual antiplatelet therapy—the MIRROR study: a randomised and double-blinded clinical trial. Eur Radiol. 2012;22(9):1998–2006. https://doi.org/10.1007/s00330-012-2441-2.

    Article  PubMed  Google Scholar 

  37. Moll F, Baumgartner I, Jaff M, et al. Edoxaban plus aspirin vs. dual antiplatelet therapy in endovascular treatment of patients with peripheral artery disease: results of the ePAD trial. J Endovasc Ther. 2018;25(2):158–68. https://doi.org/10.1177/1526602818760488.

    Article  PubMed  Google Scholar 

  38. Bonaca M, Bauersachs R, Anand S, et al. Rivaroxaban in peripheral artery disease after revascularization. J Vasc Surg. 2020;72(1):368. https://doi.org/10.1016/j.jvs.2020.04.470.

    Article  Google Scholar 

  39. Belch JJ, Dormandy J. Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. J Vasc Surg. 2010. https://doi.org/10.1016/j.jvs.2010.04.027.

    Article  PubMed  Google Scholar 

  40. Sarac TP, Huber TS, Back MR, et al. Warfarin improves the outcome of infrainguinal vein bypass grafting at high risk for failure. J Vasc Surg. 1998;28(3):446–57. https://doi.org/10.1016/s0741-5214(98)70130-2.

    Article  PubMed  CAS  Google Scholar 

  41. Dutch Bypass Oral Anticoagulants or Aspirin (BOA) Study Group. Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral anticoagulants or Aspirin study): a randomised trial. Lancet. 2000;355(9201):346–51. https://doi.org/10.1016/s0140-6736(99)07199-8.

  42. Monaco M, Di Tommaso L, Pinna GB, et al. Combination therapy with warfarin plus clopidogrel improves outcomes in femoropopliteal bypass surgery patients. J Vasc Surg. 2012;56(1):96–105. https://doi.org/10.1016/j.jvs.2012.01.004.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. AdventHealth Orlando, Orlando, FL, USA

    Kristin R. Hand

  2. Nova Southeastern University College of Pharmacy, Palm Beach Gardens, FL, USA

    Genevieve M. Hale

Authors
  1. Kristin R. Hand
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Genevieve M. Hale
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kristin R. Hand.

Ethics declarations

Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Kristin Hand and Genevieve Hale have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Author contributions

All authors participated in the interpretation of the study results and in the drafting, critical revision, and approval of the final version of the manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hand, K.R., Hale, G.M. Antithrombotic Therapy in Peripheral Artery Disease: Stepping in the Right Direction. Am J Cardiovasc Drugs 21, 523–534 (2021). https://doi.org/10.1007/s40256-021-00465-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-021-00465-x

Search

Navigation