Peripheral artery disease: Putting the updated 2024 AHA/ACC guideline into practice

Standardized terminology

The guideline encourages adopting the use of 4 standardized clinical subsets—asymptomatic; chronic symptomatic, which includes intermittent claudication (exertional leg pain); chronic limb-threatening ischemia with pain at rest, nonhealing ulceration, or gangrene attributable to arterial insufficiency; and acute limb ischemia. Chronic limb-threatening ischemia is now the preferred term instead of critical limb ischemia¹⁸ to emphasize the presence of wounds and infection alongside perfusion metrics. Consistent terminology ensures clear diagnostic thresholds, timely referrals, and standardized treatment pathways for each PAD subset. The goal is to facilitate triage, intercenter comparison, and consistent outcome reporting in registries and trials.

Screening and assessment

Targeted screening using the ankle-brachial index is recommended for the following high-risk adults:

• Anyone age 65 or older

• Those age 50 to 64 with a history of smoking or diabetes

• Those age 50 or younger with diabetes mellitus and at least 1 additional risk factor for atherosclerosis

• Those with known atherosclerotic disease in another vascular bed.

Postexercise ankle-brachial index is recommended for patients with exertional leg symptoms despite a normal or borderline ankle-brachial index.

A reasonable approach to take with patients at increased risk of PAD is performing a resting ankle-brachial index test, with or without ankle pulse volume recording or Doppler waveforms.²³ An ankle-brachial index greater than 1.40 indicates noncompressible arteries rather than normal perfusion, and toe-brachial index testing with toe pressures should be obtained when available.

Segmental pressures and multilevel pulse volume recording can help localize the disease level, while transcutaneous oxygen pressure or skin perfusion pressure may help assess local perfusion and wound-healing potential in patients with tissue loss or suspected chronic limb-threatening ischemia. A noncompressed blood vessel with an elevated ankle-brachial index is evidence of microvascular disease, which is associated with an increased risk of limb loss and concomitant systemic cardiovascular changes.

Acute limb ischemia is characterized by pain, pallor, pulselessness, poikilothermia, paresthesia, and paralysis (the 6 Ps); patients with acute limb ischemia require evaluation with Doppler waveforms.

Patients with no increased risk of PAD or who do not have history or physical examination findings do not benefit from screening.

Pharmacotherapy

Exercise therapy

Supervised exercise therapy that takes place in a hospital or outpatient setting remains a class 1 recommendation for claudication. When unavailable, structured home-based and hybrid supervised programs that use virtual coaching or wearable remote monitoring devices are evidence-based alternatives, as data show clinically significant improvements in walking distance, functional status, and quality of life (Table 3).^1,3,10–12 The guideline also recommends implementing programs with objective baseline and follow-up assessments such as ankle-brachial index, 6-minute walk test, and treadmill metrics and mechanisms to monitor patient adherence. Documenting participation and outcomes is important to support insurance coverage and reimbursement.³

Revascularization and limb preservation

The decision to undergo revascularization must be individualized based on the patient’s presentation, anatomy, conduit availability, surgical risk, response to medical and supervised exercise therapy, and goals. Choices include surgical, endovascular, and hybrid approaches.

Patients with intermittent claudication who improve adequately with medical and supervised exercise therapy should generally not undergo revascularization based solely on evidence of anatomic disease; however, revascularization can be considered for persistent, lifestyle-limiting claudication when a patient does not adequately respond to guideline-directed therapy. The treatment plan should take into account the patient’s reported disability and anatomic level of disease (ie, aortoiliac, femoropopliteal, or infrapopliteal vessels). Data indicate that endovascular treatment of infrageniculate and infrapopliteal occlusive disease may be associated with greater risk of chronic limb-threatening ischemia due in large part to procedural failures and the need for repeat interventions.¹⁸

Revascularization, when feasible, is central to limb preservation in patients with chronic limb-threatening ischemia.³ Based on results from the BEST-CLI (Best Endovascular Versus Best Surgical Therapy in Patients With Chronic Limb-Threatening Ischemia)⁶ and BASIL-2 (Bypass Versus Angioplasty for Severe Ischaemia of the Leg)⁷ trials, surgical bypass with autologous vein is favored for selected patients with chronic limb-threatening ischemia who have good conduit and acceptable operative risk. Endovascular or hybrid strategies may be preferred for patients with poor conduit, high operative risk, or anatomy favorable to an endovascular-first approach.

For patients with ischemic wounds, revascularization can restore direct arterial flow to the skin and underlying tissue where the wound is located, known as the angiosome, to promote healing.¹⁹ The guideline emphasizes that preoperative vein mapping and multidisciplinary planning are imperative before any revascularization procedure in patients with chronic limb-threatening ischemia.

Acute limb ischemia is an emergency that requires rapid assessment of limb viability and urgent consultation with a vascular specialist. Imaging should be obtained when it will not delay treatment, and revascularization strategy should be determined by limb viability, ischemia duration, anatomy, thrombotic vs embolic etiology, patient risk, and institutional expertise. Options include catheter-directed thrombolysis, pharmacomechanical or surgical thrombectomy, surgical bypass, endovascular intervention, or hybrid therapy. Irreversible ischemia requires careful assessment because revascularization may be futile or harmful.

Implementation and equity

Creating multidisciplinary chronic limb-threatening ischemia workflows requires collaborating with specialists in vascular medicine and surgery, podiatry, wound care, infectious disease, endocrinology, rehabilitation, nursing, and care coordination; implementing hub-and-spoke or embedded podiatry clinic models; stratifying outcomes such as amputation rates and time to revascularization; and expanding access to supervised exercise therapy and revascularization to underserved populations.³

Formal chronic limb-threatening ischemia care teams are not yet uniformly available across healthcare systems, but implementation can begin with the following:

• Defining automated electronic medical record–generated referral pathway for patients with pain at rest, tissue loss, or infection that uses best practice advisories driven by risk-based tools

• Expediting noninvasive testing and arterial imaging

• Standardizing wound photography and using WIfI staging (risk stratification based on wound, ischemia, and foot infection scored on a scale of 1–3) for objective evaluation¹⁷

• Involving vascular, podiatry, and wound-care specialists earlier in the process

• Tracking clinical (time to revascularization, wound healing, limb salvage, readmission) and equity metrics.

Although establishing multidisciplinary teams can be a challenge, creating quality metrics and securing financial reimbursement from private and public payers may help the process. Registries should be used to monitor patient participation and outcomes (Figure 1^{1,3,10–12,17,19–23}).

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Figure 1

Summary of multidisciplinary care team implementation and responsibilities.

Based on information from references 1, 3, 10–12, 17, and 19–23.

At Cleveland Clinic, patients with chronic limb-threatening ischemia are treated through multidisciplinary limb-salvage teams that include vascular surgery, cardiology, primary care, podiatry, and wound-care pathways, although the exact structure varies by site and clinical context.

Preventive foot care

Effective programs should educate patients on daily foot self-inspection, proper footwear, regular evaluation by podiatry, and prompt referral for wound care at the first sign of ulceration or infection.³ Clinicians should also inspect patients’ feet during routine physical examinations, evaluating skin integrity, interdigital spaces, and pulses; looking for deformity, wounds, and signs of infection; evaluating for neuropathy; and checking for appropriate footwear. Incorporating foot-care pathways into multidisciplinary PAD teams reduces the incidence of ulceration, infection, and amputation, and is an essential component of comprehensive secondary prevention.

Trial-driven strategies

COMPASS⁴ was a double-blind, randomized, placebo-controlled trial of low-dose rivaroxaban with or without aspirin in patients with stable atherosclerotic cardiovascular disease, including PAD. Rivaroxaban plus aspirin reduced major adverse cardiovascular events vs aspirin alone. A subsequent PAD subgroup analysis showed that dual-pathway inhibition reduced the risk of major adverse limb and cardiovascular events,⁸ supporting the role of dual-pathway inhibition in secondary prevention. However, this strategy requires documenting shared decision-making and monitoring for bleeding.

VOYAGER-PAD⁵ showed that rivaroxaban 2.5 mg twice daily plus aspirin in patients with PAD after lower-extremity revascularization reduced the incidence of major adverse cardiovascular and limb events vs aspirin alone. Although increased bleeding was seen, there was an overall net benefit in many subgroups, including a reduction in subsequent ischemic events.⁹ Dual-pathway inhibition should be considered in selected patients after lower-extremity revascularization, but will require postoperative antithrombotic pathways and bleeding surveillance.

Evidence from both trials supports dual-pathway inhibition to reduce the risk of major adverse limb and cardiovascular events in patients with PAD and after revascularization. This is a substantial change to the secondary-prevention strategy recommended in the 2016 guideline, and introduces broader requirements for bleeding-risk assessment and shared decision-making processes.^25,26

BEST-CLI⁶ evaluated surgical bypass with vein vs endovascular intervention in patients with chronic limb-threatening ischemia and found that bypass with a suitable autologous vein is superior for limb outcomes in selected patients. Surgical bypass should be favored when a good autologous conduit and acceptable surgical risk are present. Preoperative vein mapping should also be prioritized.

BASIL-2⁷ was a randomized trial that compared surgical bypass with best endovascular therapy for patients with chronic limb-threatening ischemia. Outcomes varied by subgroup and clinical context, but the investigators concluded that modality choice should be individualized by anatomy, conduit, comorbidity, presentation, patient goals, and local expertise.

The 2024 guideline translates these findings into practice by emphasizing the importance of venous conduit quality and patient goals. It also endorses hybrid procedures that combine surgical and endovascular approaches to offer improved reperfusion with acceptable risk.

Implementation emphasis

The updated guideline devotes more attention to how recommendations should be implemented. It includes supervised exercise therapy delivery models with virtual coaching and hybrid programs, prior authorization and insurance coverage pathways for rivaroxaban and PCSK9 inhibitors, algorithms for chronic limb-threatening ischemia teams, and equity measurements, which reflect a more pragmatic approach than the 2016 guideline.³

Risk amplifiers and health disparities

The 2024 guideline integrates conditions that amplify the risk of major adverse cardiovascular and limb events in patients with PAD, which include older age (≥ 75), diabetes, smoking and tobacco use, chronic or end-stage renal disease, polyvascular disease, microvascular disease, and depression (Table 4).^{1,3,17,20–22}

The guideline emphasizes that social determinants of health and other inequities contribute to higher amputation rates and worse cardiovascular outcomes.²⁰ Addressing racial, sex-based, and socioeconomic disparities is essential to improving vascular health in these patient populations.¹⁷

The targeted screening and community outreach recommendations substantially broaden the guideline’s public-health scope.

Key future and ongoing research areas

Shared-decision workflows

Starting a patient on dual-pathway inhibition will require informed patient consent, bleeding-risk stratification tools (HAS-BLED or OAC³-PAD), pharmacy protocols, and safety monitoring.^4,5,25,26 Clinicians will need anticoagulation referral pathways for patients to assess bleeding and renal function.

Supervised exercise therapy scaling and diversification

Clinics should implement supervised exercise therapy programs and build structured home-based and hybrid protocols with remote monitoring and virtual coaching. Tracking adherence and functional end points (eg, treadmill and 6-minute walk tests) will be necessary for reimbursement and quality reporting.^3,10–12

Multidisciplinary chronic limb-threatening ischemia care

As noted previously, healthcare systems should form chronic limb-threatening ischemia teams across specialties and establish fast-track care pathways to reduce time to revascularization and amputation rates. This approach should be paired with equity-focused outreach.^3,17,19

Revascularization patient selection and preoperative planning

All patients eligible for chronic limb-threatening ischemia revascularization should undergo preoperative vein mapping. Multidisciplinary case conferences should be used to determine the appropriate intervention (either bypass, endovascular, or hybrid). Vascular surgeons and interventionalists must coordinate around conduit preservation and staged strategies.^6,7

Quality measurement and equity work

Programs should track and publicly report equity-stratified outcomes like amputation and wound healing rates and time to revascularization, and tailor outreach and access strategies to underserved communities. This will require data infrastructure and accountability mechanisms.^20–22

Healthcare system and payer engagement

Increased interactions with third-party payers around supervised exercise therapy coverage, PCSK9 inhibitor access, and rivaroxaban reimbursement are expected. Healthcare systems should prepare budget-impact analyses and patient-assistance programs.^3,14,16

A practical framework to reduce the risk of PAD in primary care is provided in Table 5.^1,13

High bleeding risk

Patients with recent major bleeding, active bleeding, severe thrombocytopenia, or other significant bleeding conditions are typically poor candidates for dual-pathway inhibition. Individualized alternative antithrombotic strategies should be considered.^4,5

Severe frailty or limited life expectancy

In patients with very limited life expectancy or severe frailty, the risks of bypass surgery or the burden of long-term anticoagulation therapy may outweigh potential benefits. Symptom-directed care or less invasive endovascular approaches may be preferable.^6,7

Nonatherosclerotic arterial disease

Conditions such as vasculitis, nonatherosclerotic cardiac embolic disease, or thromboangiitis obliterans (Buerger disease) have distinct pathophysiologies that may require different diagnostic and therapeutic approaches.¹ The guideline recommendations will not always apply in these situations.

Low-resource settings or lack of multidisciplinary capacity

The guideline’s recommendations are dependent on timely team-based interventions (eg, fast-tracking chronic limb-threatening ischemia interventions, supervised exercise therapy programs) that may not be feasible in centers lacking infrastructure. In these settings, prioritize achievable prevention measures and referral networks while advocating for changes in the healthcare system.¹

Pediatrics and pregnancy

Research evidence is limited to adult populations; apply expert judgment and consult with specialists for younger or pregnant patients.