Guideline Updates in Lower Extremity Peripheral Artery Disease

Trista Betz, PharmD; CentraCare-Paynesville

Background: Peripheral artery disease (PAD) is an atherosclerotic disease that results in decreased blood flow to the limbs. The lower limbs are more commonly affected by PAD. This disease increases the risk of major adverse cardiovascular outcomes (MACE), such as myocardial infarction and stroke, and major adverse limb outcomes (MALE), such as amputations and critical limb ischemia. Guideline-recommended pharmacotherapies for PAD aim to reduce the risk of these major cardiovascular and limb complications as well as leg symptoms related to claudication.

Evidence/Discussion: The 2024 ACC/AHA Multisociety Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease was published in May 2024. Before this publication, the guidelines had not been updated since 2016. Evidence utilized to form these recommendations comes from human subject research from large research databases, such as Medline and Cochrane Library. Most pharmacotherapy updates focused on the utilization of antiplatelet and antithrombotic therapy. There was at least one new addition in each medication therapy section, except for the smoking cessation section which had no changes. 

The following table outlines specific medication-related changes: 

5.1  Antiplatelet and Antithrombotic Therapy for PAD

  • Recommends low-dose rivaroxaban (2.5 mg twice daily) combined with low-dose aspirin to reduce MACE and MALE in patients with symptomatic PAD or after endovascular or surgical revascularization
  • Recommends antiplatelet therapy after endovascular or surgical revascularization
  • Suggests DAPT for at least 1 to 6 months after endovascular revascularization
  • Suggests single antiplatelet after endovascular or surgical revascularization is reasonable if patient has a low risk of bleeding while on full-intensity anticoagulation for an indication other than PAD
  • Utilization of DAPT in symptomatic PAD without recent revascularization remains uncertain
  • Suggests DAPT for at least 1 month may be reasonable after surgical revascularization with a prosthetic graft
  • Recommends against full-intensity anticoagulation unless for an indication other than PAD

5.2 Lipid Lowering Therapy

  • Specifies use of high-intensity statin with goal > 50% reduction in LDL 
  • Add suggestion of PCKS9 inhibitor or ezetimibe if on max tolerated statin and LDL  > 70 mg/dL

5.3 Antihypertensive Therapy

  • States blood pressure goal of <130/80 mmHg

5.4 Smoking Cessation

  • No changes

5.5 Diabetes Management for PAD

  • Recommends GLP-1s and SGLT2is as beneficial for comorbid PAD and type II diabetes, specifically the following agents: liraglutide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin

5.6 Other Medical Therapies for Cardiovascular Risk Reduction

in PAD

  • Recommends COVID vaccine sequence including boosters
  • Evidence does not support use of vitamin D to prevent MACE

5.7 Medications for Leg Symptoms in Chronic Symptomatic

PAD

  • Added that cilostazol may be useful to reduce restenosis after endovascular therapy for femoropopliteal disease
  • Specifies that cilostazol should not be used if there is comorbid heart failure

Abbreviations: COVID, Coronavirus Disease; DAPT, dual antiplatelet therapy; GLP1, Glucagon-like Peptide-1, MACE, Major Adverse Cardiovascular Events; MALE, Major Adverse Limb Events; PAD, Peripheral Artery Disease; PCSK9, Proprotein Convertase Subtilisin/Kexin Type 9; SGLT2i, Sodium-Glucose Cotransporter-2 Inhibitors

Clinical Impact: With these updates, practitioners now have additional guidance on appropriate use of antiplatelet and antithrombotic therapy in PAD, particularly in symptomatic or revascularized PAD. It is also more specific on which therapies should be utilized for lipid and diabetes management. These guidelines offer up to date, evidence based recommendations that highlight key pharmacotherapies to reduce risk of MACE and MALE in lower extremity peripheral artery disease. 

Citations:

  1. DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey LM. DiPiro’s Pharmacotherapy : A Pathophysiologic Approach. 12th edition. McGraw Hill Medical; 2023.
  2. 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 [published correction appears in J Am Coll Cardiol. 2017 Mar 21;69(11):1521. 
  3. Gornik HL, Aronow HD, Goodney PP, et al. 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024;149(24):e1313-e1410.