What is the recommended treatment for peripheral vascular disease?

Treatment of Peripheral Vascular Disease

The recommended treatment for peripheral vascular disease begins with supervised exercise training (at least 3 times weekly for 30-45 minutes per session for minimum 12 weeks) combined with comprehensive optimal medical therapy including statin therapy (targeting LDL-C <55 mg/dL), antiplatelet therapy (aspirin 75-160 mg daily or clopidogrel 75 mg daily), and aggressive cardiovascular risk factor modification, with revascularization reserved only for patients with lifestyle-limiting symptoms who fail a 3-month trial of this conservative approach. 1, 2

Initial Management: Exercise and Medical Therapy

Supervised Exercise Training (First-Line Treatment)

• Supervised exercise training (SET) is the cornerstone of PAD treatment and should be initiated before considering any invasive procedures 1, 2
• Exercise sessions must be performed at least 3 times per week, for 30-45 minutes per session, for a minimum of 12 weeks 1, 2
• Patients should walk to moderate-severe claudication pain (77-95% maximal heart rate or 14-17 on Borg scale) for optimal benefit 2
• Sessions should be supervised by clinical exercise physiologists or physiotherapists 2
• The evidence supporting SET is Level A, making it equally important as pharmacological interventions 1, 2

Comprehensive Cardiovascular Risk Factor Modification

Lipid Management:

• All PAD patients require statin therapy regardless of baseline cholesterol levels 1, 2
• Target LDL-C <55 mg/dL (<1.4 mmol/L) with ≥50% reduction from baseline 1, 2
• For statin-intolerant patients at high cardiovascular risk not achieving LDL-C goals on ezetimibe, add bempedoic acid alone or combined with a PCSK9 inhibitor 1
• Fibrates are not recommended for cholesterol lowering 1

Blood Pressure Control:

• Target systolic blood pressure 120-129 mmHg 1, 2
• Avoid dual RAS blockade (ACE inhibitor + ARB combination) 1
• Antihypertensive therapy reduces cardiovascular events in PAD patients 2

Diabetes Management:

• Achieve tight glycemic control with HbA1c <53 mmol/mol (7%) to reduce microvascular complications 1
• SGLT2 inhibitors with proven cardiovascular benefit are recommended in patients with type 2 diabetes and PAD to reduce cardiovascular events 1
• GLP-1 receptor agonists with proven cardiovascular benefit are recommended in patients with type 2 diabetes and PAD to reduce cardiovascular events 1
• Prioritize glucose-lowering agents with proven cardiovascular benefits over agents without proven benefit or safety 1
• Avoid hypoglycemia in PAD patients 1

Smoking Cessation:

• All PAD patients who smoke must be advised to stop at every clinical encounter 1
• Offer comprehensive smoking cessation interventions including behavior modification therapy, nicotine replacement therapy, or bupropion 1

Foot Care (for diabetic PAD patients):

• Proper foot care including appropriate footwear, daily foot inspection, skin cleansing, and topical moisturizing creams should be encouraged 1
• Skin lesions and ulcerations must be addressed urgently 1

Antiplatelet Therapy

• Antiplatelet therapy with either aspirin alone (75-160 mg daily) or clopidogrel alone (75 mg daily) is recommended to reduce major adverse cardiovascular events (MACE) 1, 2
• Aspirin doses of 75-325 mg daily are safe and effective 1
• Clopidogrel 75 mg daily reduced the risk of MI, stroke, or vascular death by 23.8% compared with aspirin in PAD patients 1
• Long-term dual antiplatelet therapy (DAPT) is not recommended in PAD patients 1
• Oral anticoagulation with warfarin is not indicated to reduce cardiovascular ischemic events in PAD (unless for another indication) 1
• Routine use of ticagrelor in PAD patients is not recommended 1
• Do not systematically treat asymptomatic PAD patients without clinically relevant atherosclerotic cardiovascular disease with antiplatelet drugs 1

Pharmacological Therapy for Claudication Symptoms

Cilostazol (First-Line for Symptom Relief)

• Cilostazol (100 mg twice daily) is indicated as effective therapy to improve symptoms and increase walking distance in patients with intermittent claudication who have inadequate response to exercise alone 1, 2
• A therapeutic trial of cilostazol should be considered in all patients with lifestyle-limiting claudication, provided they do not have heart failure (absolute contraindication) 1
• Approximately 20% of patients discontinue cilostazol within 3 months due to side effects 2

Pentoxifylline (Second-Line Alternative)

• Pentoxifylline (400 mg three times daily) may be considered as second-line alternative therapy to cilostazol to improve walking distance 1
• However, the clinical effectiveness of pentoxifylline as therapy for claudication is marginal and not well established 1
• Patients on warfarin should have more frequent monitoring of prothrombin times when taking pentoxifylline 3
• Concomitant administration with theophylline-containing drugs can lead to increased theophylline levels and toxicity 3

Therapies NOT Recommended

• Chelation therapy (e.g., EDTA) is not indicated and may have harmful adverse effects 1
• The effectiveness of L-arginine, propionyl-L-carnitine, and ginkgo biloba is not well established 1

Revascularization: When Conservative Management Fails

Indications for Revascularization

• Revascularization should only be considered after a 3-month trial of optimal medical therapy and supervised exercise training in patients with persistent lifestyle-limiting symptoms and impaired quality of life 1, 2
• Endovascular procedures are indicated when there has been inadequate response to exercise or pharmacological therapy AND/OR there is a very favorable risk-benefit ratio (e.g., focal aortoiliac occlusive disease) 1
• Revascularization is NOT recommended for asymptomatic PAD 1, 2
• Revascularization is NOT recommended solely to prevent progression to chronic limb-threatening ischemia 1, 2

Endovascular Approach

• Endovascular intervention is the preferred revascularization technique for TASC type A iliac and femoropopliteal arterial lesions 1
• Stenting is effective as primary therapy for common iliac artery stenosis and occlusions 1
• Stenting is effective as primary therapy in external iliac artery stenoses and occlusions 1
• Primary stent placement is NOT recommended in the femoral, popliteal, or tibial arteries 1
• Endovascular intervention is not indicated if there is no significant pressure gradient across a stenosis despite flow augmentation with vasodilators 1

Imaging Before Revascularization

• Duplex ultrasound (DUS) is recommended as first-line imaging method to confirm PAD lesions 1
• In symptomatic patients with aorto-iliac or multisegmental/complex disease, CTA and/or MRA are recommended as adjuvant imaging techniques for preparation of revascularization procedures 1

Chronic Limb-Threatening Ischemia (CLTI)

• For limb salvage in patients with CLTI, revascularization is recommended 1
• Early recognition of CLTI and referral to the vascular team are recommended for limb salvage 1

Follow-Up Strategy

• Regular follow-up at least once annually is recommended to assess clinical and functional status, medication adherence, limb symptoms, and cardiovascular risk factors 1, 2
• Duplex ultrasound assessment should be performed as needed 1, 2
• After 3 months of optimal medical therapy and exercise, PAD-related quality of life assessment is recommended to guide further management decisions 1

Common Pitfalls to Avoid

• Do not proceed directly to revascularization without a 3-month trial of supervised exercise and optimal medical therapy unless the patient has CLTI 1, 2
• Do not use dual antiplatelet therapy routinely in PAD patients (increased bleeding risk without proven benefit) 1
• Do not use warfarin for PAD unless there is another indication (e.g., atrial fibrillation) 1
• Do not place primary stents in femoral, popliteal, or tibial arteries 1
• Do not forget that cilostazol is contraindicated in heart failure patients 1
• Do not neglect aggressive statin therapy even if baseline cholesterol is normal 1, 2