Clinical Review & Education

JAMA Clinical Guidelines Synopsis

Management of Peripheral Artery Disease

Aman Kansal, MD; Andrew M. Davis, MD, MPH; Jennifer A. Rymer, MD, MBA

GUIDELINE TITLE: 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/ or chronic limb-threatening ischemia (CLTI), low-dose

SVM/SVN/SVS/SIR/VESS Guideline for the Management of rivaroxaban (2.5 mg twice daily) combined with aspirin
Lower Extremity Peripheral Artery Disease (81 mg/d) is recommended to reduce risk of major adverse
cardiovascular events (MACE) and major adverse limb events
DEVELOPERS AND FUNDERS: American College of Cardiology (MALE) (COR: 1; LOE: A). Patients with PAD and type 2
and American Heart Association diabetes should also receive glucagon-like peptide 1 agonists
and sodium-glucose cotransporter 2 inhibitors to lower cardio-
RELEASE DATE: June 11, 2024
vascular risk of major cardiovascular events (COR: 1; LOE: A).
PRIOR VERSIONS: 2016
• Structured exercise at a pace inducing ischemic leg
symptoms, in supervised or community-based programs
TARGET POPULATION: Patientswithperipheralarterydisease(PAD) using behavioral change techniques such as health coaching
and activity tracking, is recommended for people with PAD
SELECTED RECOMMENDATIONS to improve walking performance, functional status, and
• Patients with symptoms and signs of PAD should have a quality of life (QOL) (COR: 1; LOE: A).
resting ankle-brachial index (ABI) measured, and exercise • Endovascular revascularization improves pain-free
treadmill ABI should be performed for those with normal or ambulation, walking distance, and QOL in patients with
borderline resting ABI and noncompressible arteries (class of hemodynamically significant aortoiliac or femoropopliteal
recommendation [COR]: 1; level of evidence [LOE]: B). disease and functionally limiting claudication despite
• For patients with chronic symptomatic PAD (vascular medical therapy and structured exercise (COR: 1; LOE: A).
claudication, recent revascularization, previous amputation)

Summary of the Clinical Problem resting ABI should be measured (abnormal: ⱕ0.9; borderline: 0.91-
PAD, defined as a partial or complete obstruction of at least 1 periph- 0.99; normal: 1.00-1.40; noncompressible arteries: >1.40). The ABI
eral artery due to atherosclerosis, affects more than 200 million has a sensitivity of 69% to 79% and a specificity of 83% to 99%
people worldwide.1 PAD has 4 clinical subsets: asymptomatic, for detection of PAD vs angiography. The ABI has a lower sensitivity
chronic symptomatic, CLTI, and acute limb ischemia. Established (35%-73%) in people with diabetes or chronic kidney disease, which
effective medical therapies for are associated with noncompressible tibial arteries that may elevate
Supplemental content
PAD include exercise, smoking ABI (>1.4).1
cessation,diabetesmanagement, For patients with symptomatic PAD, low-dose rivaroxaban
antiplatelet agents (aspirin or (2.5 mg twice daily) combined with low-dose aspirin (81-100 mg/d)
CME at jamacmelookup.com
P2Y12antagonists),lipid-lowering is recommended to reduce risk of MACE and MALE. In an RCT
medications, antihypertensives, and cilostazol. Patients with refrac- (n = 6391), patients treated with rivaroxaban and aspirin vs aspirin
tory symptoms or those at risk of limb loss often undergo revascular- alone had a significantly decreased rate of MALE (2.6% vs 1.5%;
ization for QOL and decreased risk of amputation. Herein we review P = .01) at a median of 21 months.2 Rivaroxaban and aspirin are also
updated recommendations for lifestyle modifications, diagnostic test- recommended for patients with prior lower extremity revascular-
ing, pharmacotherapy, and revascularization for patients with PAD.2 ization. In an RCT (n = 6564), low-dose rivaroxaban with aspirin
(vs aspirin alone) lowered incidence of MACE and MALE from 19.9%
Characteristics of the Guideline Source to 17.3% (P = .009; median follow-up, 28 months).3
The guideline committee consisted of experts in general and inter- For patients with functionally limiting PAD who have an inad-
ventional cardiology, radiology, surgery, nursing, wound care, exercise equate response to medication and exercise, endovascular revas-
physiology, podiatry, and vascular clinical research (eTable in the cularization is recommended to improve walking performance and
Supplement).2 CORwasgradedas1(strongandrecommended;n = 64), QOL. An RCT of 1830 patients with CLTI and infra-inguinal disease
2 (moderate and reasonable; n = 47), 3 (no benefit; n = 6), or 4 (harm; compared surgical bypass with endovascular revascularization. Pa-
n = 6). LOE was assigned A (high), B (moderate), or C based on quality tients who had an adequate great saphenous vein conduit for sur-
andnumberofrandomizedclinicaltrials(RCTs)ornonrandomizedtrials. gical revascularization had a lower incidence of MALE (median follow-
up, 2.7 years) vs those assigned endovascular revascularization
Evidence Base (42.6% vs 57.4%, respectively; P < .001).4 However, in an RCT of 345
For patients with claudication or non–joint-related exertional leg patients with CLTI and infrapopliteal disease, death or amputation
symptomsandsignssuggestiveofPAD(eg,pulsedeficits,legwounds), (median follow-up, 40 months) occurred more often in those

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 Clinical Review & Education JAMA Clinical Guidelines Synopsis

assigned surgical than endovascular revascularization (63% vs 53%, Discussion

respectively; P = .04).5 Thus, for patients with CLTI, retrospective PAD impairs walking and is linked to complications such as ampu-
studies suggest that a multidisciplinary team with expertise in tation, myocardial infarction, stroke, and decreased QOL. Diagno-
vascular care, revascularization, wound healing, podiatry, and foot sis involves patient history, physical examination, and ABI.2
surgery should guide treatment (COR: 1; moderate LOE).6 Addressing health disparities across geography, socioeco-
For patients with chronic symptomatic PAD, structured exer- nomic status, sex, and race and ethnicity are important to improve
cise therapy with exercise conducted at a pace that induces ische- outcomes. Black patients with PAD have a 2- to 4-fold higher risk of
mic leg symptoms is recommended. Exercise programs can be home amputation vs White patients with PAD, and this disparity in-
based and/or supervised or community-based structured pro- creases in patients aged 65 years or older.9 Potential contributors
grams. Exercise sessions should be 30 to 45 minutes at least 3 times to these disparate outcomes may include lower use of pharmaco-
a week for at least 12 weeks. The LITE trial demonstrated that low- logical therapies and less access to structured exercise programs
intensity home-based exercise conducted at a pace without ische- among Black individuals.
mic leg symptoms was significantly less effective for improving Smoking cessation is a key component of PAD care. Ongoing
6-minute walk test vs high-intensity home-based exercise.7 An- smoking is associated with a significant increase in PAD-related hos-
other RCT (190 patients with PAD and intermittent claudication) pitalizations, revascularization procedures, and health care costs.
showed that a home-based walking exercise intervention im- Five-year mortality among patients with chronic symptomatic PAD
proved 6-minute walking distance at 3 months for the intervention and active smoking is 40% to 50%.10 Up to 90% of patients pre-
group vs usual care (adjusted mean between-group difference, senting for revascularization due to severe limb symptoms (eg, se-
16.7 m; 95% CI, 4.2-29.2 m; P = .009; minimum clinically impor- vere claudication, ischemic rest pain, gangrene) are current
tant difference, 8-20 m).8 No compelling evidence supports un- smokers.10 For these patients, smoking cessation should be encour-
structured exercise for treatment of PAD. aged at every health care visit.

Potential Harms Areas in Need of Future Study or Ongoing Research

To limit procedural risks such as acute kidney injury associated with Studies are needed to determine the benefit of screening for PAD
intravenous contrast dye, allergic reactions, and discomfort, pa- in asymptomatic at-risk individuals. Novel ways to implement tele-
tients with confirmed PAD should not undergo imaging studies solely health technology effectively may improve patient access to struc-
for anatomical assessment when surgery is not being considered. tured exercise therapy, including in diverse patient populations. Re-
In addition, combination low-dose rivaroxaban (2.5 mg twice daily) search should better define optimal antiplatelet and antithrombotic
and low-dose aspirin (81-100 mg/d) may increase bleeding risk. In regimens, including drug, dose, and duration, for patients with PAD
the COMPASS trial, major bleeding was 3.2% in those treated with who have undergone revascularization. Studies comparing various
rivaroxaban and aspirin vs 2.0% with aspirin alone (P = .01).2 How- revascularization strategies, including specific devices for CLTI,
ever, major bleeding in the VOYAGER trial was not statistically dif- should address adequacy of wound healing and limb salvage, as well
ferent in those treated with rivaroxaban and aspirin vs aspirin alone as consideration of the costs and functional outcomes of multidis-
(2.7% vs 1.9%; P = .07).3 ciplinary care.

ARTICLE INFORMATION 2. Anand SS, Caron F, Eikelboom JW, et al. Major ischemia. J Vasc Surg. 2015;61(1):162-169. doi:10.
Author Affiliations: Division of Cardiology, Duke adverse limb events and mortality in patients with 1016/j.jvs.2014.05.101
University, Durham, North Carolina (Kansal, peripheral artery disease. J Am Coll Cardiol. 2018;71 7. McDermott MM, Spring B, Tian L, et al. Effect of
Rymer); Section of General Internal Medicine, (20):2306-2315. doi:10.1016/j.jacc.2018.03.008 low-intensity vs high-intensity home-based walking
University of Chicago Medicine, Chicago, Illinois 3. Bonaca MP, Bauersachs RM, Anand SS, et al. exercise on walk distance in patients with
(Davis). Rivaroxaban in peripheral artery disease after peripheral artery disease. JAMA. 2021;325(13):
Corresponding Author: Andrew M. Davis, MD, revascularization. N Engl J Med. 2020;382(21): 1266-1276. doi:10.1001/jama.2021.2536
MPH, Section of General Internal Medicine, 1994-2004. doi:10.1056/NEJMoa2000052 8. Bearne LM, Volkmer B, Peacock J, et al. Effect of
University of Chicago Medicine, 5841 S Maryland 4. Farber A, Menard MT, Conte MS, et al. Surgery or a home-based, walking exercise behavior change
Ave, Chicago, IL 60637 ([email protected]). endovascular therapy for chronic limb-threatening intervention vs usual care on walking in adults with
Published Online: July 2, 2025. ischemia. N Engl J Med. 2022;387(25):2305-2316. peripheral artery disease. JAMA. 2022;327(14):
doi:10.1001/jama.2025.8408 doi:10.1056/NEJMoa2207899 1344-1355. doi:10.1001/jama.2022.3391

Conflict of Interest Disclosures: Dr Rymer 5. Bradbury AW, Moakes CA, Popplewell M, et al. A 9. Gornik HL, Aronow HD, Goodney PP, et al. 2024
reported receipt of grants from Abiomed, Chiesi, vein bypass first versus a best endovascular ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/
Abbott, and Novo Nordisk. No other disclosures treatment first revascularisation strategy for SVS/SIR/VESS guideline for the management of
were reported. patients with chronic limb threatening ischaemia lower extremity peripheral artery disease. Circulation.
who required an infra-popliteal, with or without an 2024;149(24):e1313-e1410. doi:10.1161/CIR.
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