Antithrombotic Therapy After Peripheral Vascular Intervention

  • Peter Hu
  • Schuyler Jones
Interventional Cardiology (S Rao, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Interventional Cardiology


Cardioprotective medications and risk-factor modification are the hallmarks of treatment for all patients with peripheral artery disease (PAD). If symptoms are life-limiting and/or do not respond to conservative treatment, endovascular or surgical revascularization can be considered especially for patients with critical limb ischemia or acute limb ischemia. The rates of peripheral vascular intervention (PVI) have risen dramatically over the past few decades and much of this care have shifted from inpatient hospital settings to outpatient settings and office-based clinics. While PVI rates have surged and technology advancements have dramatically changed the face of PVI, the data behind optimal antithrombotic therapy following PVI is scant. Currently in the USA, most patients are treated with indefinite aspirin therapy and a variable duration of clopidogrel (or other P2Y12 inhibitor)—typically 1 month, 3 months, or indefinite therapy. More observational analyses and randomized clinical trials evaluating clinically relevant outcomes such as cardiovascular morbidity/mortality and the risk of bleeding are needed to guide the optimal role and duration of antithrombotic therapy post-PVI.


Peripheral artery disease Peripheral vascular intervention Aspirin Clopidogrel Antithrombotic therapy 


Compliance with Ethical Standards

Conflict of Interest

Peter Hu and Schuyler Jones declare that they have no conflict of interest.

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 •• Of major importance

  1. 1.
    Creager MA, Belkin M, Bluth EI, et al. 2012 ACCF/AHA/ACR/SCAI/SIR/STS/SVM/SVN/SVS key data elements and definitions for peripheral atherosclerotic vascular disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Data Standards. J Am Coll Cardiol [Internet]. 2012;59:294–357.CrossRefGoogle Scholar
  2. 2.
    Berger JS, Hiatt WR. Medical therapy in peripheral artery disease. Circulation. 2012;126:491–500.CrossRefPubMedGoogle Scholar
  3. 3.
    Rooke TW, Hirsch AT, Misra S, et al. 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline). Vasc Med. 2011;16:452–76.CrossRefPubMedGoogle Scholar
  4. 4.
    McDermott MM. Lower extremity manifestations of peripheral artery disease: the pathophysiologic and functional implications of leg ischemia. Circ Res [Internet]. 2015;116:1540–50.CrossRefGoogle Scholar
  5. 5.
    Pande RL, Perlstein TS, Beckman JA, et al. Secondary prevention and mortality in peripheral artery disease: national health and nutrition examination study, 1999 to 2004. Circulation. 2011;124:17–23.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Diehm C, Allenberg JR, Pittrow D, et al. Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease. Circulation. 2009;120:2053–61.CrossRefPubMedGoogle Scholar
  7. 7.
    Feringa HHH, van Waning VH, Bax JJ, et al. Cardioprotective medication is associated with improved survival in patients with peripheral arterial disease. J Am Coll Cardiol. 2006;47:1182–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Tendera M, Aboyans V, Bartelink M-L, 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 Treatm. Eur Heart J. 2011;32(22):2851–906.CrossRefPubMedGoogle Scholar
  9. 9.
    Slovut DP, Lipsitz EC. Surgical technique and peripheral artery disease. Circulation. 2012;126:1127–38.CrossRefPubMedGoogle Scholar
  10. 10.
    Goodney PP, Beck AW, Nagle J, et al. National trends in lower extremity bypass surgery, endovascular interventions, and major amputations. J Vasc Surg [Internet]. 2009;50:54–60.CrossRefGoogle Scholar
  11. 11.•
    Jones WS, Mi X, Qualls LG, Vemulapalli S, Peterson ED, Patel MR, et al. Trends in settings for peripheral vascular intervention and the effect of changes in the outpatient prospective payment system. J Am Coll Cardiol. 2015;65:920–7. This study showed the shift in PVI location from an inpatient setting to outpatient/office-based clinic setting.CrossRefPubMedGoogle Scholar
  12. 12.
    Berger JS, Krantz MJ, et al. Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials. JAMA. 2009;301(18):1909–19.CrossRefPubMedGoogle Scholar
  13. 13.
    Bonaca MP, Creager MA. Pharmacological treatment and current management of peripheral artery disease. Circ Res. 2015;116:1579–98.CrossRefPubMedGoogle Scholar
  14. 14.
    Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71–86.CrossRefGoogle Scholar
  15. 15.
    Belch JJ, Dormandy J, Committee CW, et al. Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. J Vasc Surg [Internet]. 2010;52:825–33. 833 e1–2.CrossRefGoogle Scholar
  16. 16.
    Belch J, MacCuish A, Campbell I, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Berger JS, Krantz MJ, Kittelson JM, et al. Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials. JAMA [Internet]. 2009;301:1909–19.CrossRefGoogle Scholar
  18. 18.
    Catalano M, Born G, Peto R. Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial. J Intern Med. 2007;261:276–84.CrossRefPubMedGoogle Scholar
  19. 19.
    Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA. 2010;303:841–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Bergqvist D, Almgren B, Dickinson JP. Reduction of requirement for leg vascular surgery during long-term treatment of claudicant patients with ticlopidine: results from the Swedish Ticlopidine Multicentre Study (STIMS). Eur J Vasc Endovasc Surg. 1995;10(1):69–76.CrossRefPubMedGoogle Scholar
  21. 21.
    Janzon L, Bergqvist D, Boberg J, et al. Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study. J Intern Med. 1990;227(5):301–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Gent M. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329–39.CrossRefGoogle Scholar
  23. 23.
    Cacoub PP, Bhatt DL, Steg PG, Topol EJ, Creager MA. Patients with peripheral arterial disease in the CHARISMA trial. Eur Hear J. 2009;30:192–201.CrossRefGoogle Scholar
  24. 24.
    Bhatt DL, Topol EJ. Clopidogrel added to aspirin versus aspirin alone in secondary prevention and high-risk primary prevention: rationale and design of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial. Am Hear J. 2004;148:263–8.CrossRefGoogle Scholar
  25. 25.
    AstraZeneca. A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID). In: [Internet]. Bethesda: National Library of Medicine (US). 2000- [cited 2015 Nov 1]. Available from: NLM Identifier: NCT01732822.
  26. 26.••
    Bonaca MP, Scirica BM, Creager MA, Olin J, Bounameaux H, Dellborg M, et al. Vorapaxar in patients with peripheral artery disease: results from TRA2{degrees}P-TIMI 50. Circulation [Internet]. 2013;127:1522–9. 1529e1–6. This study was a subgroup analysis from a large randomized controlled study that has led to the US Food and Drug Administration approval of vorapaxar.CrossRefGoogle Scholar
  27. 27.
    Thukkani AK, Kinlay S. Endovascular intervention for peripheral artery disease. Circ Res [Internet]. 2015;116:1599–613.CrossRefGoogle Scholar
  28. 28.
    White CJ, Gray WA. Endovascular therapies for peripheral arterial disease: an evidence-based review. Circulation. 2007;116:2203–15.CrossRefPubMedGoogle Scholar
  29. 29.
    Forte MB, Becattini C, Agnelli G. Latest developments in antithrombotic therapy in patients with lower extremity arterial disease. Rev Vasc Med [Internet]. 2014;2:37–42.CrossRefGoogle Scholar
  30. 30.
    Krajcer Z, Howell MH. Update on endovascular treatment of peripheral vascular disease: new tools, techniques, and indications. Tex Heart Inst J [Internet]. 2000;27:369–85.Google Scholar
  31. 31.
    Tepe G, Laird J, Schneider P, et al. Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial. Circulation [Internet]. 2015;131:495–502.CrossRefGoogle Scholar
  32. 32.
    Zeller T, Dake MD, Tepe G, et al. Treatment of femoropopliteal in-stent restenosis with paclitaxel-eluting stents. JACC Cardiovasc Interv [Internet]. 2013;6:274–81.CrossRefGoogle Scholar
  33. 33.
    Scheinert D, Duda S, Zeller T, et al. The LEVANT I (Lutonix paclitaxel-coated balloon for the prevention of femoropopliteal restenosis) trial for femoropopliteal revascularization: first-in-human randomized trial of low-dose drug-coated balloon versus uncoated balloon angioplasty. JACC Cardiovasc Interv [Internet]. 2014;7:10–9.CrossRefGoogle Scholar
  34. 34.
    Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med [Internet]. 2006;354:1879–88.CrossRefGoogle Scholar
  35. 35.•
    Alonso-Coello P, Bellmunt S, McGorrian C, et al. 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 [Internet]. 2012;141:e669S–90S. This is the only published guideline that has recommendations for type of anti-thrombotic therapy after PVI.CrossRefGoogle Scholar
  36. 36.
    Visonà A, Tonello D, Zalunardo B, et al. Antithrombotic treatment before and after peripheral artery percutaneous angioplasty. Blood Transfus [Internet]. 2009;7:18–23.Google Scholar
  37. 37.
    Tendera M, Aboyans V, Bartelink M-L, 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 Treatm. Eur Heart J [Internet]. 2011;32:2851–906.CrossRefGoogle Scholar
  38. 38.
    Robertson L, Ghouri MA, Kovacs F. Antiplatelet and anticoagulant drugs for prevention of restenosis/reocclusion following peripheral endovascular treatment. Cochrane Database Syst Rev [Internet]. 2012;8:CD002071.Google Scholar
  39. 39.
    Jones WS, Dolor RJ, Hasselblad V, et al. Comparative effectiveness of endovascular and surgical revascularization for patients with peripheral artery disease and critical limb ischemia: systematic review of revascularization in critical limb ischemia. Am Hear J. 2014;167:489–98. e7.CrossRefGoogle Scholar
  40. 40.
    Milani RV. Antiplatelet therapy after endovascular intervention: does combination therapy really work and what is the optimum duration of therapy? Catheter Cardiovasc Interv. 2009;74 Suppl 1:S7–S11.CrossRefPubMedGoogle Scholar
  41. 41.
    Allemang MT, Rajani RR, Nelson PR, et al. Prescribing patterns of antiplatelet agents are highly variable after lower extremity endovascular procedures. Ann Vasc Surg. 2013;27(1):62–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Koppensteiner R, Spring S, Amann-Vesti BR, et al. Low-molecular-weight heparin for prevention of restenosis after femoropopliteal percutaneous transluminal angioplasty: a randomized controlled trial. J Vasc Surg [Internet]. 2006;44:1247–53.CrossRefGoogle Scholar
  43. 43.
    Cho S, Ko Y-G, Shin D-H, et al. Abstract 14976: impact of the duration of dual antiplatelet therapy in patients with peripheral arterial occlusive disease after percutaneous transluminal angioplasty on clinical outcomes. Circulation [Internet]. 2014;130:A14976 –.Google Scholar
  44. 44.
    Banerjee S, University of Texas Southwestern Medical Center. Antiplatelet Strategy for Peripheral Arterial Interventions for Revascularization of Lower Extremities (ASPIRE PAD). In: [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Sep 1]. Available from: NLM Identifier: NCT02317822.
  45. 45.
    Kashyap VS, University Hospital Case Medical Center. Evaluation of short versus long duration dual antiplatelet therapy in patients undergoing lower extremity endovascular revascularization. In: [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Sep 1]. Available from: NLM Identifier: NCT02433587.
  46. 46.
    Arkansas Heart Hospital. Ticagrelor and peripheral arterial disease. In: [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2015 Sep 1]. Available from: NLM Identifier: NCT02407314.

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of MedicineDuke University Medical CenterDurhamUSA
  2. 2.Duke Clinical Research InstituteDuke University Medical CenterDurhamUSA

Personalised recommendations