Peripheral Arterial Occlusive Disease (PAOD)

Diagnosis and management overview - Fuster & Hurst's The Heart, 15th Edition

Definition

• Harrison's Principles of Internal Medicine 22e (2025)

Epidemiology and Risk Factors

• Peak prevalence in the sixth and seventh decades of life
• Prevalence is similar in men and women
• Higher prevalence in Black individuals than non-Hispanic white individuals
• Associated with lower socioeconomic status

• Harrison's 22e; Fuster & Hurst's The Heart, 15e

Pathology

• Atherosclerotic plaques with calcium deposition
• Thinning of the media
• Patchy destruction of muscle and elastic fibers
• Fragmentation of the internal elastic lamina
• Platelet-fibrin thrombi

• Abdominal aorta and iliac arteries - 30% of symptomatic patients
• Femoral and popliteal arteries - 80-90% of patients (most common; the superficial femoral artery accounts for ~70% of cases)
• Tibial and peroneal arteries - 40-50% of patients (more common in elderly and diabetics)

• Harrison's 22e

Clinical Presentation

Symptoms - Progressive Spectrum

• Pain, ache, cramp, numbness, or fatigue in muscles during exercise, relieved by rest (not by stopping and leaning - which distinguishes it from spinal stenosis/neurogenic claudication)
• Site of claudication is distal to the occlusive lesion:
  • Aortoiliac disease: buttock, hip, thigh claudication + impotence = Leriche's syndrome
  • Femoral-popliteal disease: calf claudication (most common)
  • Tibial/peroneal disease: calf and foot claudication

• Rest pain: Worse at night, improved by hanging foot out of bed or sleeping in a chair (gravity restores perfusion pressure). Even the weight of bedclothes exacerbates it.
• Ischemic ulcers: Painful erosions between toes or shallow non-healing ulcers on the dorsum of the feet, shins, and malleoli
• Gangrene: Blackened, mummified tissue; superadded infection makes it "wet"

• Pain (severe, sudden onset)
• Pallor
• Pulselessness
• Paresthesia
• Paralysis
• Perishing cold (poikilothermia)

• Harrison's 22e; Bailey & Love's Short Practice of Surgery, 28e

Physical Examination

• Bailey & Love's, 28e

Classification

Fontaine Classification (Symptom-Based)

Rutherford Classification

Anatomic Classification

• TASC II (Trans-Atlantic Inter-Society Consensus): classifies lesions A-D based on extent; guides endovascular vs. surgical approach
• GLASS (Global Limb Anatomic Staging System): newer system for CLTI
• Fuster & Hurst's The Heart, 15e

Investigation

Ankle-Brachial Index (ABI)

Vascular Laboratory / Imaging

• Harrison's 22e; Bailey & Love's, 28e

Treatment

1. Risk Factor Modification (for Cardiovascular Risk Reduction)

• Smoking cessation: Single most important intervention. Use counseling + NRT/bupropion/varenicline.
• Statins (high-intensity): Mandatory in all PAD patients. Aim for ≥50% LDL reduction (2018 AHA/ACC guideline). Also reduce adverse limb events including amputation.
• PCSK9 inhibitors: If target not reached on statin; also reduce limb events.
• Antihypertensives: ACE inhibitors/ARBs preferred (reduce cardiovascular events). Beta-blockers do not worsen claudication and can be used for coexisting CAD.
• Glycemic control: Intensive glucose lowering reduces amputation risk. GLP-1 agonists and SGLT2 inhibitors have additional cardiovascular and limb benefits in diabetic PAD patients.

2. Antiplatelet / Antithrombotic Therapy

• Antiplatelet therapy (aspirin or clopidogrel): Recommended for all symptomatic PAD patients.
• Clopidogrel vs. aspirin: Outcomes are similar; clopidogrel is an acceptable first-line choice.
• Dual antiplatelet therapy (DAPT): Benefit over monotherapy in PAD uncertain; increased bleeding risk.
• Vorapaxar (PAR-1 antagonist): Reduces cardiovascular events and acute limb ischemia when added to existing antiplatelet therapy, but increases bleeding.
• Rivaroxaban 2.5 mg BD + aspirin: The COMPASS regimen - improves cardiovascular and limb outcomes in established PAD and after revascularization, but increases bleeding risk.
• Warfarin is not indicated for chronic PAD (no benefit over antiplatelet, more bleeding).

3. Claudication-Specific Therapies

• Supervised exercise training: 30-45 min sessions, ≥3 times/week for ≥12 weeks. Improves walking distance - often equivalent to or better than revascularization for claudication.
• Cilostazol (PDE-3 inhibitor): Increases walking distance by ~50%. Contraindicated in heart failure.
• Foot care: moisturizing creams, well-fitting protective shoes. Avoid elastic compression hose (reduces arterial flow).

4. CLTI-Specific Supportive Measures

• Bed elevation via shock blocks under the bed head (increases gravitational perfusion pressure)
• Bed canopy over the feet (protects from bedcloth pressure)

5. Revascularization

• Percutaneous transluminal angioplasty (PTA) ± stenting
• Drug-eluting balloons / stents
• TASC A & B lesions generally amenable to endovascular approach
• Caution: paclitaxel-coated devices raised mortality signal in meta-analyses

• Bypass grafting (aortofemoral, femoropopliteal, femorodistal)
• Autologous vein graft preferred for infrapopliteal bypass (better long-term patency)
• Endarterectomy (for focal iliac/common femoral disease)
• TASC C & D lesions typically require surgery
• Open surgery preferred when rapid flow restoration (<24 h) is necessary to prevent limb loss

• Harrison's 22e; Fuster & Hurst's, 15e; Bailey & Love's, 28e

Acute Limb Ischemia - Management

1. IV heparin anticoagulation to prevent clot propagation and re-embolism
2. Confirm diagnosis with Doppler, duplex US, CTA, MRA or catheter arteriography

• Catheter-directed thrombolysis (rt-PA, reteplase, tenecteplase): Most effective for acute thrombus in atherosclerotic vessels, grafts, or stents; when surgery is contraindicated; for distal inaccessible vessels. Requires intensive monitoring for hemorrhage.
• Percutaneous mechanical thrombectomy: Uses hydrodynamic or rotational devices; usually combined with pharmacologic thrombolysis.
• Surgical thromboembolectomy / bypass: Preferred when flow must be restored within 24 hours to prevent limb loss.
• Amputation: For non-viable limb (loss of sensation, paralysis, no Doppler flow in arteries or veins).

• Harrison's 22e

Systemic Risk and Prognosis

• Myocardial infarction (50% have coexisting coronary disease)
• Stroke (25-50% have coexisting cerebrovascular disease)
• Cardiovascular death

Sources

• Harrison's Principles of Internal Medicine, 22nd Edition (2025) - Chapter 292
• Fuster & Hurst's The Heart, 15th Edition - Chapter 26
• Bailey & Love's Short Practice of Surgery, 28th Edition - Chapter 61
• Recent PubMed evidence: Toe-brachial index meta-analysis [PMID: 39474992, Cochrane 2024]; TG-glucose index and PAD meta-analysis [PMID: 39341836, 2024]

Peripheral Arterial Occlusive Disease

As per Sabiston Textbook of Surgery (The Biological Basis of Modern Surgical Practice)

Overview and Pathophysiology

• Aortoiliac occlusive disease (AIOD)
• Femoropopliteal disease (most common segment)
• Infrapopliteal / tibial disease (more common in diabetics and elderly)

Epidemiology and Risk Factors

• Prevalence has increased with the aging population, rising obesity rates, and as a complication of diabetes mellitus (DM)
• Many patients are asymptomatic; approximately 10% of patients with PAD have intermittent claudication
• Of all PAD patients with intermittent claudication, about 21% will have progression of disease over 5 years, with an amputation rate of approximately 1%
• Patients with both PAD and DM have a lower extremity amputation rate of 5%, vs. 1.5% for non-diabetic PAD patients
• Minor amputations are 4.6 times more likely in patients with both diagnoses vs. PAD alone
• A twofold increased risk of minor amputations if baseline HbA1c >7%

• Diabetes mellitus
• Smoking / tobacco use
• Hypertension
• Hyperlipidemia
• Chronic kidney disease
• Obesity
• Age

• Patients with PAD and concomitant CAD have higher composite MACE rates (15.3% vs. 8.9%; HR 1.50)
• Patients with prior MI and PAD have double the cardiovascular risk compared to PAD alone (19.3% vs. 8.4%)

Clinical Presentation

Spectrum of Disease

• Defined as pain, fatigue, or numbness in the lower extremities with activity that is relieved by rest
• About 10% of all PAD patients have IC
• 5-year risk of limb amputation is 5% and predicted 5-year life expectancy is 75-80% (relatively preserved)
• The majority of patients with IC will maintain current function or decline slowly

• Defined as arterial occlusive disease causing greater than 2 weeks of symptoms of rest pain or tissue loss with diagnostic study findings confirming arterial insufficiency
• CLTI is an advanced progression of PAD that may lead to minor or major amputation if left untreated
• Less than 5% of patients with PAD progress to CLTI
• A systematic review showed a major amputation rate of 22% if CLTI is left untreated
• Patients with CLTI have 50% 5-year mortality and a much higher amputation risk (compared to IC)

• Defined as an arterial occlusion with associated symptoms present for less than 2 weeks
• A surgical emergency; irreversible muscle and nerve injury can occur after 6 hours of severe arterial insufficiency
• Incidence: approximately 1.5 cases per 10,000 persons per year
• Associated with high morbidity and mortality: perioperative mortality rates 20-40%, limb loss rates 12-50%

The "Six Ps" of Acute Limb Ischemia

1. Pain
2. Pulselessness
3. Poikilothermia (coolness)
4. Paresthesia
5. Pallor
6. Paralysis

Classification Systems

Fontaine Classification (Historical - clinical symptoms only)

Rutherford Classification (Clinical symptoms + noninvasive data; separates chronic and acute)

Key principle from Sabiston: Irreversibly ischemic limbs (Category III) with major tissue loss or permanent nerve damage with profound sensory/motor loss should be treated with primary extremity amputation. Revascularization of a nonviable extremity in rigor should be avoided as it could lead to multisystem organ failure and death.

SVS WIfI Classification (Wound, Ischemia, Foot Infection) - Table 103.1

TASC II Classification (Anatomic - guides endovascular vs. surgical approach)

• Published 2000, modified 2007
• Divides lesions into aortoiliac and femoropopliteal segments
• Groups lesion patterns by severity (A to D):
  • TASC A & B: Focal/limited disease → endovascular therapy recommended
  • TASC C & D: Longer, more severe lesions → surgical bypass recommended

GLASS (Global Limb Anatomic Staging System)

• Newer anatomic classification for CLTI, used with WIfI to guide revascularization strategy
• The GLASS stage (y-axis) combined with WIfI limb risk (x-axis) determines preferred initial revascularization strategy

Diagnostic Modalities

Noninvasive Vascular Studies

• Cornerstone non-invasive test
• ABI = Highest ankle systolic BP (posterior tibial or dorsalis pedis) / Highest brachial systolic BP
• ABI ≤0.90 = PAD (diagnostic)
• In CLTI:
  • Ischemia Grade 0: ABI ≥0.80
  • Grade 1: ABI 0.60-0.79
  • Grade 2: ABI 0.40-0.59
  • Grade 3: ABI ≤0.39
• When vessels are calcified and non-compressible (ABI >1.40, common in diabetes): use toe pressure (TP) or transcutaneous oxygen pressure (TcPO₂)

Imaging

• Non-invasive; good for femoropopliteal segments
• Operator-dependent; limited in calcified/obese patients
• Can image slow flow (2 cm/s) in infrapopliteal vessels

• Excellent for aortoiliac disease; useful for operative planning
• Limited in distal, calcified lower extremity vessels (calcification creates artifact impairing stenosis characterization)
• Advances: dual-energy CTA with bone removal protocols, ultra-high-resolution CT with subtraction techniques are improving assessment

• Most accurate in meta-analysis comparing contrast-enhanced MRA, duplex, and CTA for lesions with >50% stenosis
• Avoids ionizing radiation; longer acquisition times
• Ability to image blood flow as slow as 2 cm/s - improves imaging of infrapopliteal vessels and identifies bypass targets not seen on DSA (especially in diabetics)
• Emerging techniques: plaque composition assessment, skeletal muscle perfusion, non-contrast methods

• Fluoroscopic technique; intraarterial contrast injection with subtracted images
• Invasive; carries risk of complications
• Key advantage: concurrent therapeutic endovascular intervention at time of imaging
• Intravascular ultrasound (IVUS) can be used as an adjunct during angiography to measure arterial dimensions for balloon/stent sizing and to assess post-intervention results

Non-Interventional (Medical) Management

1. Prevent progressive atherosclerosis - reduce Major Adverse Cardiovascular Events (MACEs) (nonfatal stroke + nonfatal MI + cardiovascular death)
2. Medically optimize patients before revascularization (better surgical outcomes)
3. After revascularization: reduce Major Adverse Limb Events (MALEs) (reinterventions, amputations)

Antithrombotic Therapy

• Multiple RCTs have demonstrated benefit of single antiplatelet therapy for secondary prevention (reduce MI, stroke, death) in PAD
• In asymptomatic PAD: conflicting data for primary prevention (no coexisting CAD/CVD); single antiplatelet may be reasonable in those with reduced ABI and low bleeding risk
• 2022 USPSTF guidance: recommended against initiating aspirin for primary prevention of MACE in the general adult population (ages 40-59: only small net benefit for those with ≥10% 10-year CVD risk; ages ≥60: recommends against)
• Note: USPSTF guidance was for primary prevention - PAD patients with established atherosclerosis are candidates for secondary prevention

Smoking Cessation

Exercise Therapy

• Supervised exercise therapy is the preferred initial management strategy for IC (along with optimal medical management)
• A systematic review of 10 RCTs (1087 patients) found endovascular revascularization did not provide significant benefit compared to supervised exercise alone for functional performance or quality-of-life
• Exception (CLEVER Trial): In IC secondary to aortoiliac disease, both supervised exercise AND endovascular revascularization improved functional status and quality of life

Treatment of Asymptomatic Disease and Intermittent Claudication

• SVS guidelines: Recommend against invasive treatments for PAD in asymptomatic patients, regardless of hemodynamic measures or imaging findings (in the absence of a threatened bypass graft or stent)
• Cornerstone = lifestyle change + medical therapy to address cardiovascular risk factors
• IC patients are at relatively low risk of adverse outcomes (5-year amputation risk 5%; 5-year life expectancy 75-80%)
• 20-30% of IC patients will develop disability significant enough to warrant intervention
• Indications for intervention in IC (SVS Appropriate Use Criteria 2022):
  1. Lifestyle-altering symptoms
  2. After failure of exercise and medical therapy
  3. Favorable anatomic factors
  4. Prolonged patency and symptom relief likely
• For femoropopliteal disease: reserve invasive interventions for severe, lifestyle-limiting IC
• For common femoral artery (CFA) disease: open endarterectomy provides greater net benefit than endovascular intervention
• Tibial artery interventions for IC: of unclear benefit; can lead to worsening of PAD and increased risk of limb loss - not recommended

Treatment of Chronic Limb-Threatening Ischemia (CLTI)

• CLTI patients have 50% 5-year mortality and much higher amputation risk than IC patients
• Prognosis determined primarily by limb stage at presentation

Selection of Revascularization Strategy

• TASC II (2007): Open bypass recommended for TASC C and D (longer, severe lesions); endovascular for TASC A and B
• Note: TASC classifications did not correlate well with expected patency rates (limitation acknowledged)

• BASIL Trial (2005): Bypass Versus Angioplasty in Severe Ischaemia of the Leg - randomized, controlled, multicenter; established foundation for decision-making in infrainguinal CLTI
• Preferred strategy for infrainguinal disease is determined by GLASS anatomic stage (y-axis) vs. WIfI limb risk (x-axis) (Figure 103.12)

Open Surgical Revascularization

• Aortofemoral bypass (standard for AIOD)
  • End-to-end or end-to-side proximal anastomosis; graft beveled 60 degrees
  • Profundaplasty: when DFA and SFA are diseased; preserves long-term patency of anatomic and extraanatomic grafts
  • Patent IMA or accessory renal arteries may be reimplanted

• Used in high-risk patients or hostile abdomen

• Autologous vein is preferred conduit for infrapopliteal bypass
• Femoral triangle anatomy is key: CFA lies lateral to the common femoral vein; DFA exits posterolaterally; great saphenous vein enters anteromedially
• Common femoral artery (CFA) endarterectomy: open surgery preferred for CFA disease

Endovascular Techniques

• Percutaneous transluminal angioplasty (PTA) ± stenting
• Drug-eluting balloons and stents
• For aortoiliac: endovascular approach for TASC A/B lesions

Acute Limb Ischemia - Management

• Other causes: traumatic injury, aortic dissection, hemodynamic compromise (shock, vasopressors)

• Systemic anticoagulation (prefer agents that allow titration and quick reversal)
• CTA may be the fastest diagnostic tool to guide the operative approach
• Additional diagnostics: echocardiogram (identify embolic sources), aortic cross-sectional imaging, full pulse exam + Doppler, percutaneous arteriography, MRA

• Endovascular, open, or hybrid based on anatomy and urgency
• Time to therapy is critical for preserving limb tissue and function

• Four-compartment fasciotomy of the lower extremity should always be considered after revascularization, especially if ischemia time >6 hours

• Category III (Irreversible) ALI → primary amputation (avoid revascularization of nonviable limb in rigor - risk of multisystem organ failure and death)
• Primary amputation also best for patients with poor overall health, devastating tissue loss especially with non-ambulatory status
• Determining the appropriate amputation level requires: full pulse examination + Doppler ultrasonography, CTA, arterial ultrasound, percutaneous arteriography, or MRA

Post-Revascularization

• Specific antithrombotic therapies reduce MALEs (reinterventions and amputations) after revascularization
• Postrevascularization surveillance programs are important for graft patency monitoring
• Assessment of outcomes includes patency rates, limb salvage, and quality-of-life metrics