Treatment of Peripheral Arterial Occlusive Disease (PAOD)
First-Line Treatment: Comprehensive Medical Therapy Before Any Revascularization
All patients with PAOD must receive comprehensive cardiovascular risk reduction—including antiplatelet therapy, high-intensity statin, blood pressure control, smoking cessation, and supervised exercise training—as initial treatment for at least 3 months before considering revascularization, which is reserved only for those with persistent lifestyle-limiting symptoms after optimal medical therapy. 1, 2
Antiplatelet Therapy (Mandatory for All Symptomatic Patients)
Clopidogrel 75 mg once daily is the preferred antiplatelet agent to reduce myocardial infarction, stroke, and vascular death in all symptomatic PAOD patients. 1, 2, 3
Aspirin 75–325 mg daily is an acceptable alternative if clopidogrel is not tolerated. 1, 2
For high-risk patients without high bleeding risk, add rivaroxaban 2.5 mg twice daily to aspirin 100 mg daily to further reduce cardiovascular and limb events, especially after lower-limb revascularization. 1, 2, 4
Dual antiplatelet therapy (aspirin + clopidogrel) is NOT routinely recommended for stable PAOD because it increases bleeding risk without additional cardiovascular benefit. 1, 2
Never add warfarin to antiplatelet therapy without a specific indication (e.g., atrial fibrillation), as it provides no benefit and significantly increases major bleeding. 1, 2
Lipid Management (Immediate and Aggressive)
Start high-intensity statin therapy immediately upon PAOD diagnosis, targeting LDL-C <1.4 mmol/L (55 mg/dL) with a ≥50% reduction from baseline. 1
If target LDL-C is not achieved on maximally tolerated statin, add ezetimibe. 1
If target is still not met on statin + ezetimibe, add a PCSK9 inhibitor (evolocumab or alirocumab). 1
For statin-intolerant patients, use bempedoic acid alone or combined with a PCSK9 inhibitor. 1
Fibrates are NOT recommended for cholesterol lowering in PAOD patients. 1, 4
Blood Pressure Control
Target systolic blood pressure 120–129 mmHg if tolerated to reduce cardiovascular risk. 1
ACE inhibitors or ARBs should be considered as first-line antihypertensive therapy in PAOD patients. 1
Beta-blockers are NOT contraindicated in PAOD and are effective antihypertensive agents. 1, 4
In patients ≥85 years, with severe frailty, or symptomatic orthostatic hypotension, consider a more lenient target (<140/90 mmHg). 1
Supervised Exercise Training (Class I, Level A Recommendation)
Supervised exercise training (SET) is the initial treatment for intermittent claudication and must be attempted before any revascularization. 1, 2
Exercise Prescription Parameters:
- Frequency: ≥3 sessions per week 1, 2
- Duration: 30–60 minutes per session 1, 2
- Program length: Minimum 12 weeks 1, 2
- Intensity: High-intensity (77–95% of maximal heart rate or Borg scale 14–17) yields the greatest improvements in walking performance and cardiorespiratory fitness. 1, 2
- Modality: Walking is the first-line training activity. 1, 2
- Pain level: Exercise to moderate-severe claudication pain to maximize walking distance gains. 1, 2, 4
When SET is unavailable, offer structured home-based exercise training (HBET) with remote monitoring (telephone calls, logbooks, or connected devices), although it is inferior to supervised programs. 1, 2
For patients who undergo endovascular revascularization, continue SET as adjunctive therapy to maintain functional gains. 1, 2
Pharmacologic Therapy for Claudication Symptoms
Cilostazol 100 mg twice daily should be prescribed for all patients with lifestyle-limiting claudication to improve symptoms and walking distance. 1, 2, 5
Cilostazol is contraindicated in patients with heart failure. 1, 2
Pentoxifylline 400 mg three times daily may be used as a second-line alternative, although its clinical benefit is marginal and not well established. 1, 5
Other agents (L-arginine, propionyl-L-carnitine, ginkgo biloba) have marginal or unestablished effectiveness, and chelation therapy is not indicated and may be harmful. 1
Smoking Cessation (Critical for All Patients)
Ask about tobacco use at every encounter, provide counseling, and develop a quit plan with pharmacotherapy for all PAOD patients who smoke. 1, 4
Offer one or more of: varenicline, bupropion, or nicotine replacement therapy, unless contraindicated. 1, 4
E-cigarettes may be considered as an aid to quit smoking, but limit their use and avoid simultaneous use with conventional cigarettes due to unknown long-term effects. 1
Indications for Revascularization (Only After 3-Month Trial of Medical Therapy)
Revascularization should be considered ONLY after a 3-month trial of optimal medical therapy and supervised exercise in patients with persistent lifestyle-limiting symptoms and impaired quality of life. 1, 2
Mandatory Criteria Before Proceeding:
- Completion of supervised exercise and pharmacotherapy with inadequate symptomatic response 1, 2
- Significant disability affecting work or important daily activities 1, 2
- Ongoing comprehensive risk-factor modification and antiplatelet therapy 1, 2
- Lesion anatomy that presents low procedural risk and high probability of immediate and long-term technical success 1, 2
After the 3-month period, reassess PAOD-related quality of life; revascularization may be pursued if quality of life remains impaired. 1, 2
For femoro-popliteal lesions, drug-eluting endovascular therapy is the preferred first-line strategy. 1, 2
Open surgical bypass using autologous vein should be considered in low-risk patients when a suitable vein is available. 1, 2
Revascularization is NOT recommended solely to prevent progression to critical limb-threatening ischemia (CLTI) and is NOT indicated in asymptomatic PAOD. 1, 2
Evidence Supporting Conservative Approach:
- The CLEVER trial demonstrated that supervised exercise training produced superior treadmill walking performance at 6 months compared with primary stenting for aorto-iliac PAOD. 1, 2
- A Dutch retrospective cohort of 54,504 patients showed that those undergoing revascularization (endovascular or open) had higher rates of secondary procedures and increased 5-year mortality compared with SET alone. 1, 2
- The IRONIC trial demonstrated that revascularization lost its early benefit at 5 years, with no long-term improvement in quality of life or walking capacity compared with optimal medical therapy + SET alone. 1
Critical Limb-Threatening Ischemia (CLTI): Medical Emergency
Early recognition of CLTI and immediate referral to a vascular team are essential for limb salvage. 1, 2
CLTI Management:
- Expedited evaluation and treatment of factors that increase amputation risk (diabetes, neuropathy, chronic renal failure, infection). 1, 2
- Revascularization should be performed as soon as possible to restore direct pulsatile flow to at least one foot artery, preferably the artery supplying the wound region. 1, 2
- Systemic antibiotics should be started promptly in CLTI patients with skin ulcerations or evidence of infection. 1, 2
- Off-loading of mechanical tissue stress is indicated for CLTI-related ulcers to facilitate wound healing. 1, 2, 4
- Patients at risk for CLTI (ABI <0.4 with diabetes or any diabetic with known PAOD) should undergo regular foot inspection. 1, 2
- "Time is tissue" in infected ischemic diabetic foot ulcers—treat as a medical urgency, preferably within 24 hours. 1
Acute Limb Ischemia: Vascular Emergency
In patients with acute limb ischemia and a salvageable extremity, emergent evaluation of the occlusion level and prompt endovascular or surgical revascularization are required. 1
Early onset of anticoagulation is recommended to limit thrombus propagation until definitive therapy can be employed. 1
Cross-sectional imaging with CTA or MRA is recommended to reveal the exact nature and level of thrombosis and underlying atherosclerotic plaque. 1
If the limb is non-viable, vascular anatomy evaluation and revascularization attempts should not be performed. 1
Follow-Up and Surveillance
All PAOD patients should have at least annual follow-up to assess clinical status, medication adherence, limb symptoms, and cardiovascular risk factors; duplex ultrasound is performed as needed. 1, 2, 4
Patients with a prior history of CLTI or who have undergone successful CLTI treatment should be evaluated at least twice yearly by a vascular specialist because of the high recurrence risk. 1, 2
Long-term patency of infra-inguinal bypass grafts should be monitored through a surveillance program that includes vascular history, resting ABI, physical examination, and periodic duplex ultrasound. 1, 2
Post-revascularization surveillance: ABI and arterial duplex ultrasound at 1–3 months, 6 months, 12 months, then annually. 4
Patients at risk for or treated for CLTI should receive verbal and written instructions for self-surveillance of recurrence. 1, 2
Common Pitfalls to Avoid
Do NOT proceed directly to revascularization without first completing a 3-month trial of optimal medical therapy and supervised exercise in patients with intermittent claudication. 1, 2
Do NOT add warfarin to antiplatelet therapy without a clear indication, as it increases bleeding risk without cardiovascular benefit. 1, 2
Do NOT prescribe cilostazol to patients with heart failure because it is contraindicated. 1, 2
Do NOT delay referral to a vascular team in patients with CLTI; early recognition and treatment are critical for limb salvage. 1, 2
Do NOT perform arterial imaging in patients with a normal post-exercise ABI unless alternative diagnoses (e.g., entrapment syndromes) are suspected. 2