Peripheral Artery Disease

Details of the Concept

Lower extremity peripheral artery disease (PAD) is atherosclerotic and thrombotic disease of the aortoiliac, femoropopliteal, and infrapopliteal arterial segments. It is one of the most prevalent cardiovascular diseases globally and is associated with significant morbidity, mortality, functional impairment, and major adverse limb events (MALE). The 2024 ACC/AHA multi-society guideline is the current authoritative management standard. sources/PVD-AHA-2024

Epidemiology

• Estimated 10–12 million affected in the United States in individuals >40 years of age
• Worldwide prevalence estimated at 113–236 million (estimates vary considerably)
• Prevalence >15% in adults >80 years of age
• Lifetime risk: ~30% in Black men/women; ~19–22% in White and Hispanic populations — Black patients develop PAD earlier and at higher burden sources/PVD-AHA-2024

Four Clinical Subsets

Key Facts

Diagnosis

• ABI is the cornerstone diagnostic test: abnormal ≤0.90, borderline 0.91–0.99, normal 1.00–1.40, noncompressible >1.40. Sensitivity 69–79%, specificity 83–99% vs imaging → see concepts/Ankle-Brachial-Index
• TBI ≤0.70 for patients with non-compressible vessels (diabetes/CKD); absolute toe pressure <30 mmHg = severe ischaemia
• ABI screening: COR 2a for high-risk patients (age ≥65; age 50–64 + risk factors/CKD; <50 + diabetes + risk factor; known polyvascular disease); COR 3:No Benefit for low-risk, asymptomatic individuals sources/PVD-AHA-2024
• Imaging (duplex US, CTA, MRA) indicated to plan revascularisation; COR 3:Harm for anatomic assessment when revascularisation not being considered sources/PVD-AHA-2024

PAD-Related Risk Amplifiers (increase MACE and/or MALE)

• Diabetes: OR for developing PAD up to 4×; HR 1.35 all-cause death; 5.48× increased amputation risk
• Ongoing smoking: 5-y mortality 40–50% in chronic symptomatic PAD; OR 2.4 for developing symptomatic PAD; risk remains >2× elevated for 10–20 years post-cessation
• CKD (eGFR <60): HR 1.45 for cardiovascular death/MI/stroke; up to 25% of CKD patients have PAD
• ESKD (dialysis): up to 45% PAD prevalence; dramatically lower 5-y survival (19% vs 48% post-renal transplant)
• Polyvascular disease (≥2 atherosclerotic beds): stepwise MACE increase (HR 1.47 → 2.33 → 3.12 per additional bed); combination with diabetes gives highest event rate (~60%)
• Microvascular disease: 12–22.7-fold increased amputation risk
• Depression: 13% higher amputation rate; 17% higher mortality (VA population)
• Age ≥75: frailty highly predictive of 30-day post-revascularisation mortality sources/PVD-AHA-2024

Guideline-Directed Medical Therapy (GDMT)

Antiplatelet/antithrombotic:

• Single antiplatelet therapy (aspirin 75–325 mg/day or clopidogrel 75 mg/day): COR 1 for symptomatic PAD. Clopidogrel marginally superior to aspirin (CAPRIE)
• Rivaroxaban 2.5 mg BID + aspirin 81 mg/day: COR 1A — reduces both MACE and MALE in symptomatic PAD (COMPASS) and after revascularisation (VOYAGER PAD). Contraindicated if high bleeding risk, prior stroke/intracranial haemorrhage
• After endovascular revascularisation: DAPT for at least 1–6 months (COR 2a)
• Full-intensity oral anticoagulation (without separate indication): COR 3:Harm sources/PVD-AHA-2024

Lipid-lowering:

• High-intensity statin (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) targeting ≥50% LDL-C reduction: COR 1A
• Statin meta-analysis: MALE risk ↓30%, amputation ↓35%, all-cause death ↓39%
• Add PCSK9 inhibitor (COR 2a) or ezetimibe (COR 2a) if LDL-C ≥70 mg/dL on maximal statin sources/PVD-AHA-2024

Antihypertensive:

• Target SBP <130 mmHg, DBP <80 mmHg: COR 1 B-R
• ACEi or ARB first-line (HOPE: ramipril reduced MI/stroke/vascular death by 25% in PAD subgroup): COR 1 B-R sources/PVD-AHA-2024

Smoking cessation:

• Advise at every visit: COR 1A. Pharmacotherapy (varenicline + counselling most effective): COR 1A sources/PVD-AHA-2024

Diabetes:

• GLP-1 agonists (liraglutide, semaglutide) and SGLT-2 inhibitors (canagliflozin, dapagliflozin, empagliflozin): COR 1A for T2DM + PAD
• Canagliflozin amputation signal from CANVAS was not reproduced in CREDENCE or subsequent meta-analysis; black-box warning removed 2020 sources/PVD-AHA-2024

Leg symptom medications:

• Cilostazol COR 1A for claudication; contraindicated in heart failure of any severity (COR 3:Harm)
• Pentoxifylline: COR 3:No Benefit sources/PVD-AHA-2024

Exercise Therapy

• Supervised exercise therapy (SET): COR 1A — as effective as revascularisation for claudication; minimum 3×/week for 12 weeks; treadmill walking to moderate-severe claudication; Medicare covered
• Structured community-based/home exercise with behavioural change: COR 1A — equally effective alternative
• SET as initial treatment option for functionally limiting claudication before revascularisation: COR 1 B-R
• Referral rate remains ~2% in the US despite coverage and evidence sources/PVD-AHA-2024

Revascularisation

• Asymptomatic PAD: revascularisation to prevent disease progression is COR 3:Harm; only reasonable to facilitate other necessary procedures (e.g., TAVR, EVAR)
• Claudication: revascularisation is second-tier after GDMT + exercise; endovascular COR 1A for aortoiliac/femoropopliteal disease; autogenous vein preferred for femoropopliteal bypass (COR 1A)
• CLTI: revascularisation is standard of care; multispecialty team evaluation mandatory before amputation → see concepts/CLTI
• ALI: vascular emergency; revascularisation COR 1A for salvageable limb → see concepts/Acute-Limb-Ischemia

Health Disparities

• Black patients: 2–4× higher amputation risk; more frequent CLTI presentation; lower revascularisation and GDMT rates; lower SET participation
• Women: present 10–20 years later with more atypical symptoms; greater risk of above-knee amputation; underrepresented in RCTs
• Rural patients: greater amputation risk, older, higher comorbidity burden, less health care access
• PAD National Action Plan: 6 strategic goals; aim of 20% nontraumatic amputation reduction by 2030 (AHA) sources/PVD-AHA-2024

ESC 2024 — where it diverges from the ACC/AHA position

• PAD is reframed as one half of "PAAD", peripheral arterial and aortic disease, with a Class I/B recommendation to adopt "a comprehensive approach that addresses the entirety of the arterial circulation." The organisational consequence: every PAD patient is screened for aortic disease, and vice versa. (sources/AD-PAD-ESC-2024, rating: very high)
• ABI ≤0.90 remains the diagnostic criterion (I/B), with toe pressure, toe-brachial index or Doppler waveform analysis when vessels are non-compressible or ABI >1.40.
• Antiplatelet therapy loses its aspirin default. Aspirin 75–160 mg or clopidogrel alone is Class I/A; clopidogrel may be preferred over aspirin (IIb/B); aspirin is not indicated in asymptomatic PAD without clinically relevant ASCVD (III/B); long-term DAPT (III/A), oral anticoagulant monotherapy (III/A) and routine ticagrelor (III/A) are all not recommended.
• Low-dose rivaroxaban 2.5 mg twice daily plus aspirin 100 mg is recommended for high ischaemic and non-high bleeding risk (IIa/A), and after lower-limb revascularisation (IIa/B) — the same COMPASS/VOYAGER-PAD regimen, promoted from "consider" to a named strategy.
• Risk-factor targets are tighter than in 2018: LDL-C <1.4 mmol/L with >50% reduction (I/A), blood pressure toward 120–129 mmHg (I/A), HbA1c <53 mmol/mol (I/A), and both SGLT2 inhibitors and GLP-1 receptor agonists with proven CV benefit as Class I/A in type 2 diabetes with PAD.
• Supervised exercise therapy is Class I/A and the default for claudication; revascularisation is IIb/B and only after three months of medical therapy and exercise with impaired quality of life. Revascularisation is not recommended in asymptomatic PAD (III/C), nor solely to prevent progression to CLTI (III/B).
• Revascularisation technique is specified by segment: drug-eluting treatment first-choice in femoropopliteal disease (IIa/A); balloon angioplasty ± stenting in external iliac, primary stenting in common iliac (IIa/B).

Contradictions / Open Questions

• BEST-CLI vs BASIL-2: BEST-CLI shows surgical bypass superior for CLTI with adequate saphenous vein (HR 0.68); BASIL-2 shows endovascular superior for infrapopliteal-dominant disease (HR 1.35 favouring endovascular). These contrasting results require individualised decision-making incorporating anatomy, conduit availability, patient risk, and preferences. sources/PVD-AHA-2024
• Rivaroxaban + aspirin bleeding risk: COMPASS/VOYAGER PAD show significant MACE/MALE benefit but also increased major bleeding. Net clinical benefit varies by patient bleeding risk profile and is not established for all subpopulations (e.g., very elderly, prior stroke). sources/PVD-AHA-2024
• Canagliflozin amputation signal: CANVAS showed elevated amputation rate; not reproduced in CREDENCE or meta-analysis; FDA removed black-box warning. Ongoing uncertainty in highest-risk PAD subpopulations. sources/PVD-AHA-2024
• The two guidelines give different first-line antiplatelet advice. ACC/AHA 2024 treats aspirin as the default with clopidogrel as an alternative; ESC 2024 makes them equivalent (I/A) and permits clopidogrel to be preferred (IIb/B). Neither grades the choice above the other, and no head-to-head trial in PAD settles it.
• Infrapopliteal claudication revascularisation: effectiveness unknown for both endovascular and surgical approaches (COR 2b C-LD); most evidence comes from CLTI populations. sources/PVD-AHA-2024

Connections

• Related to concepts/CLTI
• Related to concepts/Acute-Limb-Ischemia
• Related to concepts/Ankle-Brachial-Index
• Related to entities/Hypertension
• Related to entities/Chronic-Coronary-Disease (polyvascular disease overlap)
• Related to entities/Heart-Failure (cilostazol contraindicated in HF)
• Related to concepts/Dyslipidemia
• Related to concepts/ASCVD-Risk-Assessment

Sources

• sources/PVD-AHA-2024
• sources/AD-PAD-ESC-2024