Skip to main content
SpringerLink
Log in

Pharmacologic Interventions in Patients with Peripheral Arterial Disease

  • Chapter
  • First Online:
Peripheral Arterial Interventions

Part of the book series: Contemporary Cardiology ((CONCARD))

  • 254 Accesses

Abstract

Pharmacologic preventative therapies in the peripheral arterial disease (PAD) patients improve long-term mortality and morbidity. The use of antiplatelets in symptomatic patients with PAD is recommended, and clopidogrel is preferred over aspirin. Although ticagrelor and vorapaxar reduced major adverse cardiovascular and limb events in certain subgroups of PAD patients, this came at the expense of increase in bleeding. Cilostazol reduced claudication and restenosis post-vascular intervention. Lipid-lowering agents, statins and PCSK9 inhibitors, have been shown to reduce cardiovascular events in patients with PAD. Recently, SGLT2 inhibitors and GLP agonists also showed a reduction in the risk of adverse cardiovascular events in patients with atherosclerotic vascular disease and type 2 diabetes including the PAD patients. All patients with PAD should be considered for aggressive pharmacological management that is likely to positively impact their overall major adverse cardiovascular and limb events.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Fowkes FGR, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013;382:1329–40.

    Article  Google Scholar 

  2. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease). Circulation. 2006;113:e463–654. https://doi.org/10.1161/CIRCULATIONAHA.106.174526.

    Article  PubMed  Google Scholar 

  3. Kumbhani DJ, Steg PG, Cannon CP, et al. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry. Eur Heart J. 2014;35:2864–72.

    Article  CAS  Google Scholar 

  4. Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley diabetes study. Circulation. 1995;91:1472–9.

    Article  CAS  Google Scholar 

  5. Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015;116:1509–26.

    Article  CAS  Google Scholar 

  6. Steg PG, Bhatt DL, Wilson PW, et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA. 2007;297:1197–206.

    Article  CAS  Google Scholar 

  7. Nehler MR, Duval S, Diao L, et al. Epidemiology of peripheral arterial disease and critical limb ischemia in an insured national population. J Vasc Surg. 2014;60(3):686–95.e2.

    Article  Google Scholar 

  8. Bonaca MP, Nault P, Giugliano RP, Keech AC, Pineda AL, Kanevsky E, Kuder J, Murphy SA, Jukema JW, Lewis BS, et al. Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease: insights from the FOURIER trial (further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk). Circulation. 2018;137:338–50. https://doi.org/10.1161/CIRCULATIONAHA.117.032235.

    Article  CAS  PubMed  Google Scholar 

  9. Sigvant B, Hasvold P, Kragsterman B, et al. Cardiovascular outcomes in patients with peripheral arterial disease as an initial or subsequent manifestation of atherosclerotic disease: results from a Swedish Nationwide Study. J Vasc Surg. 2017;66:507–514.e1.

    Article  Google Scholar 

  10. Ankle Brachial Index Collaboration. Ankle brachial index combined with Framingham risk score to predict cardiovascular events and mortality. A meta-analysis. JAMA. 2008;300:197–208.

    Article  Google Scholar 

  11. Gutierrez JA, Mulder H, Jones WS, Rockhold FW, Baumgartner I, Berger JS, Blomster JI, Fowkes FGR, Held P, Katona BG, et al. Polyvascular disease and risk of major adverse cardiovascular events in peripheral artery disease: a secondary analysis of the EUCLID trial. JAMA Netw Open. 2018;1:e185239. https://doi.org/10.1001/jamanetworkopen.2018.5239.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, 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. https://doi.org/10.1136/bmj.a1840.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fowkes FG, Price JF, Stewart MC, Butcher I, Leng GC, Pell AC, Sandercock PA, Fox KA, Lowe GD, Murray GD. Aspirin for Asymptomatic Atherosclerosis Trialists 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. https://doi.org/10.1001/jama.2010.221.

    Article  CAS  PubMed  Google Scholar 

  14. Aboyans V, Ricco J-B, Bartelink M-L, et al. 2017 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. Eur Heart J. 2018;39:763–816. https://doi.org/10.1093/eurheartj/ehx095.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  Google Scholar 

  16. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2017;69(11):e71–e126.

    Article  Google Scholar 

  17. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348:1329–39. https://doi.org/10.1016/s0140-6736(96)09457-3.

    Article  Google Scholar 

  18. Cacoub PP, Bhatt DL, Steg PG, et al. Patients with peripheral arterial disease in the CHARISMA trial. Eur Heart J. 2009;30:192.

    Article  CAS  Google Scholar 

  19. Bhatt DL, Flather MD, Hacke W, et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007;49:1982.

    Article  Google Scholar 

  20. Bonaca MP, Bhatt DL, Storey RF, Steg PG, Cohen M, Kuder J, Goodrich E, Nicolau JC, Parkhomenko A, López-Sendón J, et al. Ticagrelor for prevention of ischemic events after myocardial infarction in patients with peripheral artery disease. J Am Coll Cardiol. 2016;67:2719–28. https://doi.org/10.1016/j.jacc.2016.03.524.

    Article  CAS  PubMed  Google Scholar 

  21. Hiatt WR, Fowkes FGR, Heizer G, et al. Ticagrelor versus clopidogrel in symptomatic peripheral artery disease. N Engl J Med. 2017;376:32–40. https://doi.org/10.1056/NEJMoa1611688. Epub 2016 Nov 13.

    Article  CAS  PubMed  Google Scholar 

  22. Secemsky EA, Yeh RW, Kereiakes DJ, Cutlip DE, Steg PG, Massaro JM, Apruzzese PK, Mauri L, Dual Antiplatelet Therapy Study Investigators. Extended duration dual antiplatelet therapy after coronary stenting among patients with peripheral arterial disease: a subanalysis of the dual antiplatelet therapy study. JACC Cardiovasc Interv. 2017;10:942–54. https://doi.org/10.1016/j.jcin.2017.02.013.

    Article  PubMed  Google Scholar 

  23. Franzone A, Piccolo R, Gargiulo G, Ariotti S, Marino M, Santucci A, Baldo A, Magnani G, Moschovitis A, Windecker S, 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;1:795–803. https://doi.org/10.1001/jamacardio.2016.2811.

    Article  PubMed  Google Scholar 

  24. Jennings LK. Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost. 2009;102:248–57.

    Article  CAS  Google Scholar 

  25. Coughlin SR. Thrombin signalling and protease-activated receptors. Nature. 2000;407:258–64.

    Article  CAS  Google Scholar 

  26. Bonaca MP, Scirica BM, Creager MA, et al. Vorapaxar in patients with peripheral artery disease: results from TRA2°P-TIMI 50. Circulation. 2013;127:1522–9.

    Article  CAS  Google Scholar 

  27. Deerhake ME, Tricoci P. Vorapaxar: the drug and its applications. https://www.acc.org/latest-in-cardiology/articles/2016/05/18/13/58/vorapaxar. Accessed 2 May 2021.

  28. 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. 2012;141:e669S–90S.

    Article  CAS  Google Scholar 

  29. Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM, Anand SS, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377:1319–30. https://doi.org/10.1056/NEJMoa1709118.

    Article  CAS  PubMed  Google Scholar 

  30. Anand SS, Bosch J, Eikelboom JW, Connolly SJ, Diaz R, Widimsky P, Aboyans V, Alings M, Kakkar AK, Keltai K, et al. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2018;391(10117):219–29. https://doi.org/10.1016/S0140-6736(17)32409-1. Epub 2017 Nov 10.

    Article  CAS  PubMed  Google Scholar 

  31. Bonaca MP, Bauersachs RM, Anand SS, Debus ES, Nehler MR, Patel MR, et al. Rivaroxaban in peripheral artery disease after revascularization. N Engl J Med. 2020;382(21):1994–2004.

    Article  CAS  Google Scholar 

  32. Anand S, Yusuf S, Xie C, Pogue J, Eikelboom J, Budaj A, et al. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease warfarin antiplatelet vascular evaluation trial investigators. N Engl J Med. 2007;357(3):217–27. https://doi.org/10.1056/NEJMoa065959.

    Article  CAS  PubMed  Google Scholar 

  33. Moll F, Baumgartner I, Jaff M, Nwachuku C, Tangelder M, Ansel G, Adams G, Zeller T, Rundback J, Grosso 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;25:158–68. https://doi.org/10.1177/1526602818760488.

    Article  PubMed  Google Scholar 

  34. Thompson PD, Zimet R, Forbes WP, Zhang P. Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication. Am J Cardiol. 2002;90:1314–9.

    Article  CAS  Google Scholar 

  35. Dawson DL, Cutler BS, Hiatt WR, et al. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med. 2000;109:523–30.

    Article  CAS  Google Scholar 

  36. Iida O, Nanto S, Uematsu M, Morozumi T, Kitakaze M, Nagata S. Cilostazol reduces restenosis after endovascular therapy in patients with femoropopliteal lesions. J Vasc Surg. 2008;48:144–9.

    Article  Google Scholar 

  37. Soga Y, Yokoi H, Kawasaki T, et al. Efficacy of cilostazol after endovascular therapy for femoropopliteal artery disease in patients with intermittent claudication. J Am Coll Cardiol. 2009;53:48–53.

    Article  CAS  Google Scholar 

  38. Lida O, Yokoi H, Soga Y, et al. Cilostazol reduces angiographic restenosis after endovascular therapy for femoropopliteal lesions in the sufficient treatment of peripheral intervention by Cilostazol study. Circulation. 2013;127:2307–15.

    Article  Google Scholar 

  39. Heart Protection Study Collaborative Group. Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions. J Vasc Surg. 2007;45:645–54; discussion 653–654.

    Article  Google Scholar 

  40. Badjatiya A, Merrill P, Buse JB, et al. Clinical outcomes in patients with type 2 diabetes mellitus and peripheral artery disease: results from the EXSCEL trial. Circ Cardiovasc Interv. 2019;12(12):e008018. https://doi.org/10.1161/CIRCINTERVENTIONS.119.008018. Epub 2019 Nov 22.

    Article  PubMed  Google Scholar 

  41. Verma S, Rasmussen S, Saevereid HA, Ripa MS. Abstract 11456: liraglutide and semaglutide reduce cardiovascular events in patients with type 2 diabetes and peripheral arterial disease originally published 11 Nov 2019. Circulation. 2019;140:A11456.

    Google Scholar 

  42. Verma S, Mazer CD, Al-Omran M, Inzucchi SE, Fitchett D, Hehnke U, George JT, Zinman B. Cardiovascular outcomes and safety of Empagliflozin in patients with type 2 diabetes mellitus and peripheral artery disease. Circulation. 2018;137:405–7.

    Article  Google Scholar 

  43. Bonaca MP, Wiviott SD, Zelniker TA, et al. Dapagliflozin and cardiac, kidney, and limb outcomes in patients with and without peripheral artery disease in DECLARE-TIMI 58. Circulation. 2020;142:734–47.

    Article  Google Scholar 

  44. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644–57.

    Article  CAS  Google Scholar 

  45. Matthews DR, Li Q, Perkovic V, et al. Effects of canagliflozin on amputation risk in type 2 diabetes: the CANVAS program. Diabetologia. 2019;62:926–38.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Midwest Cardiovascular Research Foundation, Davenport, IA, USA

    Qais Radaideh & Nicolas W. Shammas

Authors
  1. Qais Radaideh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicolas W. Shammas
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Midwest Cardiovascular Research Foundation, Davenport, IA, USA

    Nicolas W. Shammas

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Radaideh, Q., Shammas, N.W. (2022). Pharmacologic Interventions in Patients with Peripheral Arterial Disease. In: Shammas, N.W. (eds) Peripheral Arterial Interventions. Contemporary Cardiology. Springer, Cham. https://doi.org/10.1007/978-3-031-09741-6_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-09741-6_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-09740-9

  • Online ISBN: 978-3-031-09741-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation