2024 ACC/AHA Guideline for the Management of Lower Extremity Peripheral Artery Disease

Authors, Journal, Affiliations, Type, DOI

• Authors: Heather L. Gornik (Chair), Herbert D. Aronow, Philip P. Goodney (Co-Vice Chairs), + 26 writing committee members
• Journal: Circulation, 2024;149:e1313–e1410
• Collaborating organisations: ACC, AHA, AACVPR, APMA, ABC, SCAI, SVM, SVN, SVS, SIR, VESS
• Type: Clinical Practice Guideline (full revision of 2016 guideline); literature search October 2020–June 2022, updated to May 2023
• DOI: 10.1161/CIR.0000000000001251

Overview

The 2024 ACC/AHA multi-society guideline is a comprehensive update to the 2016 guideline for lower extremity peripheral artery disease (PAD), covering atherosclerotic and thrombotic disease of the aortoiliac, femoropopliteal, and infrapopliteal arterial segments. It defines four clinical subsets of PAD, provides evidence-graded recommendations for diagnosis and management, and introduces new emphasis on health disparities, exercise therapy, multispecialty CLTI care, and key findings from the COMPASS, VOYAGER PAD, BEST-CLI, and BASIL-2 trials. The guideline applies to all patients with lower extremity PAD from asymptomatic disease through acute limb ischemia.

Keywords

Acute limb ischemia, angioplasty, ankle-brachial index, anticoagulation, antiplatelet therapy, antithrombotic therapy, claudication, chronic limb-threatening ischemia, critical limb ischemia, diabetes, diagnostic testing, endovascular therapy, exercise rehabilitation, foot care, lipid lowering, medical management, peripheral artery disease, peripheral vascular disease, smoking cessation, statin, stenting, thrombolysis, vascular surgery

Key Takeaways

Clinical Assessment (Section 2)

• PAD is classified into 4 clinical subsets: asymptomatic PAD (20–59% of objectively confirmed PAD; may have functional impairment), chronic symptomatic PAD (claudication and exertional leg symptoms), CLTI (rest pain, nonhealing wounds, gangrene >2 wk; 1-y mortality 25–35%; 1-y amputation up to 30%), and ALI (<2 wk; incidence 1.7% in symptomatic PAD cohort over 30 mo)
• Patients at increased risk for PAD: age ≥65; age 50–64 with atherosclerosis risk factors, CKD, or family history of PAD; age <50 with diabetes + 1 risk factor; known atherosclerotic disease in another vascular bed
• ABI screening for high-risk patients is COR 2a; screening of low-risk, asymptomatic patients is COR 3: No Benefit

Diagnostic Testing (Section 3)

• Resting ABI is COR 1 for suspected PAD; reported as: abnormal (≤0.90), borderline (0.91–0.99), normal (1.00–1.40), noncompressible (>1.40)
• TBI (toe-brachial index) ≤0.70 defines PAD when ABI >1.40 (noncompressible arteries — common in diabetes/CKD); absolute toe pressure <30 mmHg = severe ischemia
• Exercise treadmill ABI: COR 1 when resting ABI is normal/borderline with exertional symptoms; COR 2a to objectively assess functional status when ABI ≤0.90
• Imaging (duplex US, CTA, MRA, catheter angiography): COR 1 for planning revascularization in claudication or CLTI; COR 3:Harm for anatomic assessment when revascularization is not being considered
• TcPO2 >30 mmHg or SPP >40 mmHg predicts wound healing in CLTI

Risk Amplifiers and Health Disparities (Section 4)

• PAD-related risk amplifiers for increased MACE/MALE: diabetes (HR 1.35 all-cause death), ongoing smoking (5-y mortality 40–50% in chronic symptomatic PAD), CKD (HR 1.45 cardiovascular death/MI/stroke), ESKD (up to 45% prevalence of PAD in dialysis patients), polyvascular disease (atherosclerosis in ≥2 beds; stepwise MACE increase), microvascular disease (12–22.7-fold increased amputation risk), depression (13% higher amputation rate)
• GLP-1/SGLT-2 combination of polyvascular disease + diabetes has the highest cardiovascular event rate (~60%)
• Health disparities: Black patients have lifetime PAD risk ~30% vs ~19% White; 2–4× higher amputation risk; lower rates of revascularization, GDMT prescription, and SET participation; structural racism and social determinants of health are explicitly addressed
• Women with PAD present 10–20 years later, more atypically, with worse functional status; greater risk of above-knee vs below-knee amputation
• Rural patients at greater amputation risk; geographic and socioeconomic barriers compound racial disparities
• Older patients (≥75 y): geriatric syndromes (frailty, sarcopenia, malnutrition, mobility impairment) worsen outcomes; frailty is highly predictive of 30-day mortality after revascularization

Medical Therapy and Preventive Foot Care (Section 5)

Antiplatelet/antithrombotic therapy:

• Single antiplatelet therapy (aspirin 75–325 mg/day OR clopidogrel 75 mg/day) COR 1 for symptomatic PAD
• Clopidogrel monotherapy had improved efficacy vs aspirin in CAPRIE (similar bleeding)
• Rivaroxaban 2.5 mg BID + aspirin 81 mg/day is COR 1A for both symptomatic PAD (COMPASS) and post-revascularization PAD (VOYAGER PAD) to reduce MACE and MALE; contraindicated at high bleeding risk or history of stroke/intracranial hemorrhage
• After endovascular revascularization: DAPT with P2Y12 + aspirin for at least 1–6 months (COR 2a)
• Full-intensity oral anticoagulation (without separate indication) is COR 3:Harm — WAVE trial showed no benefit and increased bleeding

Lipid-lowering therapy:

• High-intensity statin (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) targeting ≥50% LDL-C reduction: COR 1A
• Statin therapy reduces MALE risk by 30%, amputation by 35%, all-cause death by 39% (meta-analysis of 138,060 patients)
• PCSK9 inhibitor if LDL-C ≥70 mg/dL on maximal statin: COR 2a (FOURIER: evolocumab HR 0.63 for MALE; ODYSSEY: alirocumab HR 0.59 for MALE)
• Ezetimibe if LDL-C ≥70 mg/dL on maximal statin: COR 2a

Antihypertensive therapy:

• Antihypertensive therapy COR 1A; target SBP <130/80 mmHg
• ACEi or ARB are first-line for PAD + hypertension (HOPE trial: ramipril reduced MI/stroke/vascular death by 25% in PAD subgroup)
• Beta-blockers do not worsen claudication; no adverse MALE signal

Smoking cessation:

• COR 1A at every visit; pharmacotherapy (varenicline, bupropion, nicotine replacement) combined with counselling increases cessation rate 2–3× over self-quit; 5-y mortality 40–50% with active smoking + chronic symptomatic PAD
• Risk of PAD remains >2× elevated for up to 10–20 years post-cessation; does not return to non-smoker risk for ~30 years

Diabetes management:

• GLP-1 agonists (liraglutide, semaglutide) and SGLT-2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) reduce MACE in T2DM + PAD: COR 1A
• Canagliflozin black-box warning for lower-extremity amputation (CANVAS trial: 6.3 vs 3.4/1000 patient-years) was removed by FDA August 2020 after not being reproduced in CREDENCE or subsequent meta-analysis
• Glycemic control (HbA1c) associated with MALE reduction but evidence is observational (COR 2b)

Other medical therapies:

• Annual influenza vaccination: COR 1; SARS-CoV-2 vaccination: COR 1
• Mediterranean diet: COR 2a B-R for MACE reduction in high-risk patients
• B-complex vitamins, chelation therapy, and vitamin D are COR 3:No Benefit for MACE prevention

Medications for leg symptoms:

• Cilostazol (phosphodiesterase III inhibitor) COR 1A for claudication symptom improvement and walking distance; contraindicated in heart failure of any severity (COR 3:Harm)
• Cilostazol COR 2b for restenosis reduction after femoropopliteal endovascular therapy
• Pentoxifylline: COR 3:No Benefit for claudication

Preventive foot care:

• Foot inspection at every visit COR 1; comprehensive annual foot evaluation COR 1; therapeutic footwear for high-risk feet COR 1
• Risk factors for foot ulcers/amputation: previous ulcer/amputation, Charcot deformity, diabetes with poor glycemic control, CKD/ESKD, peripheral neuropathy, corns/calluses, ongoing smoking

Exercise Therapy (Section 6)

• SET (Supervised Exercise Therapy) is COR 1A to improve walking performance, functional status, and QOL; at least 30–45 min active walking/session, ≥3 sessions/week for minimum 12 weeks; Medicare covered
• Structured community-based/home exercise with behavioural change techniques: COR 1A — equally effective alternative
• SET after revascularization is also COR 1A (further improves outcomes beyond revascularization alone)
• For functionally limiting claudication: SET or community exercise should be offered as initial treatment option (COR 1 B-R) before revascularization
• CLEVER trial: SET = endovascular revascularization for aortoiliac disease at 6 and 18 months; both superior to medical care alone
• Referral rates for SET remain very low (~2%) in the United States despite coverage and evidence
• Unstructured exercise ("go out and walk") is COR 2b — not shown to improve outcomes

Revascularization for Asymptomatic PAD (Section 7)

• Revascularization to facilitate other necessary procedures (e.g., TAVR, EVAR): COR 2a
• Revascularization solely to prevent disease progression: COR 3:Harm — no evidence supports this; patients post-revascularization have increased risk of subsequent MALE

Revascularization for Claudication (Section 9)

• Revascularization is second-tier treatment for claudication — only after inadequate response to GDMT including structured exercise
• For aortoiliac and femoropopliteal disease: endovascular revascularization is COR 1A; surgical revascularization is COR 2a (if perioperative risk acceptable and technical factors favor surgery)
• Combined revascularization + SET produces greater functional improvement than either alone (multiple RCTs and meta-analyses)
• Common femoral artery disease: surgical endarterectomy preferred (COR 2a; 78.5% primary patency at 7 years); endovascular COR 2b for high-surgical-risk patients
• Autogenous vein bypass preferred over prosthetic for femoropopliteal surgical revascularization: COR 1A
• Revascularization for isolated infrapopliteal claudication: COR 2b (effectiveness unknown; typically reserved for CLTI)

Management of CLTI (Section 10)

• Multispecialty care team evaluation is mandatory before amputation (except life-threatening sepsis): COR 1
• Revascularization (surgical/endovascular/hybrid) when feasible: COR 1 B-R to minimise tissue loss and preserve functional limb
• BEST-CLI trial (patients with both surgical and endovascular options): Cohort 1 (adequate single-segment saphenous vein) — surgical bypass superior to endovascular (primary composite outcome 42.6% vs 57.4%, HR 0.68; driven by lower repeat revascularization)
• BASIL-2 trial (infrapopliteal-dominant disease): endovascular superior to bypass for death/major amputation (53% vs 63%; HR 1.35); difference driven by fewer deaths in endovascular group
• Contrasting BEST-CLI and BASIL-2 findings require individualisation based on anatomy, conduit availability, comorbidities, and patient preferences
• Autogenous vein (single-segment great saphenous vein) preferred for bypass to popliteal/infrapopliteal arteries: COR 1A
• Ultrasound vein mapping before bypass: COR 1 B-R
• Direct revascularisation to wound bed (angiosome-directed) associated with lower amputation rates and superior wound healing vs indirect revascularisation
• Pressure offloading for diabetic foot ulcers: COR 1A; nonremovable devices superior to removable

Wound Care and "No-Option" CLTI (Section 10.3)

• Wound care + infection management are adjuncts to revascularisation
• Negative pressure wound therapy (NPWT): COR 2a for wound healing
• For "no-option" patients: spinal cord stimulation, intermittent pneumatic compression, and venous arterialization (percutaneous deep vein arterialization — LimFlow) are emerging strategies
• PROMISE I trial of pDVA (LimFlow): amputation-free survival 70% at 12 months in 31 patients

Acute Limb Ischemia (Section 11)

• ALI is defined as acute (≤2 wk) limb hypoperfusion; skeletal muscle tolerates ischaemia ~4–6 hours
• Rutherford classification: Class I (viable, not threatened) → IIa (marginally threatened) → IIb (immediately threatened) → III (irreversible/nonsalvageable)
• Initial evaluation uses continuous-wave Doppler at bedside; absence of both arterial and venous Doppler signals = likely irreversible (Class III)
• Revascularisation (endovascular or surgical): COR 1A for salvageable limb; both approaches show similar limb salvage rates (4 RCTs), with higher bleeding risk with thrombolysis
• Ultrasound-accelerated catheter-based thrombolysis: lower lytic agent amount and faster thrombolysis time vs standard catheter thrombolysis (single RCT)
• Pharmacomechanical/vacuum-assisted thrombectomy: emerging; limb salvage >80% in case series
• Compartment syndrome monitoring mandatory after revascularisation; prophylactic fasciotomy COR 2a for Category IIa/IIb
• Revascularisation of nonsalvageable (Category III) limb: COR 3:Harm
• After ALI: diagnostic evaluation for cause (embolism, thrombosis, trauma, peripheral aneurysm) is COR 1

Longitudinal Follow-Up (Section 12)

• Regular follow-up for all PAD patients; reassess leg symptoms, pulses, and feet at each visit
• Higher frequency monitoring for high-risk patients (CLTI, previous amputation, multiple risk amplifiers)

PAD National Action Plan and Advocacy (Section 13)

• 6 strategic goals: improve awareness, detection, and treatment of PAD nationally
• Goal of 20% reduction in nontraumatic limb amputation by 2030 (AHA)
• Increasing representation of Black and other underrepresented groups in PAD clinical trials is an explicit advocacy priority

Limitations of the Document

• Literature search ended June 2022 (with supplemental updates to May 2023); some newer data not captured
• Most RCTs of revascularisation and exercise therapy enrolled predominantly White male participants; generalisability to women and underrepresented racial/ethnic groups is limited
• Evidence for infrapopliteal claudication revascularisation is sparse; effectiveness unknown (COR 2b C-LD)
• BASIL-2 and BEST-CLI have contrasting results for CLTI revascularisation strategy; individualization required and evidence gaps remain
• Guideline limited to atherosclerotic/thrombotic lower extremity disease; does not address vasculitis, fibromuscular dysplasia, entrapsment syndromes, paediatric disease, or isolated microangiopathy
• Cost-value analysis not systematically performed

Key Concepts Mentioned

• concepts/Ankle-Brachial-Index — cornerstone diagnostic test for PAD; ABI classification system; TBI for non-compressible vessels
• concepts/CLTI — definition, WIfI/GLASS staging, revascularisation strategy (BEST-CLI/BASIL-2), multispecialty care
• concepts/Acute-Limb-Ischemia — Rutherford classification, 4–6 h ischaemia window, revascularisation algorithm
• concepts/PAD-Exercise-Therapy — SET as initial treatment for claudication; CLEVER trial; community-based programs
• concepts/PAD-Medical-Therapy — rivaroxaban + aspirin; high-intensity statin; ACEi/ARB; GLP-1/SGLT-2i; cilostazol

Key Entities Mentioned

• entities/Peripheral-Artery-Disease — the primary disease entity; 10–12 million affected in the US; 113–236 million worldwide
• entities/COMPASS-Trial — rivaroxaban 2.5 mg BID + aspirin reduces MACE and MALE in stable CVD including PAD
• entities/VOYAGER-PAD-Trial — rivaroxaban 2.5 mg BID + aspirin reduces MACE/MALE after PAD revascularisation
• entities/BEST-CLI-Trial — surgical bypass superior to endovascular for CLTI with adequate saphenous vein
• entities/BASIL-2-Trial — endovascular superior to bypass for infrapopliteal-dominant CLTI

Wiki Pages Updated

• wiki/sources/PVD-AHA-2024.md (created)
• wiki/sourceindex.md (updated)
• wiki/wikiindex.md (updated)
• wiki/entities/Peripheral-Artery-Disease.md (created)
• wiki/concepts/CLTI.md (created)
• wiki/concepts/Acute-Limb-Ischemia.md (created)
• wiki/concepts/Ankle-Brachial-Index.md (created)