Treatment of Peripheral Vascular Disease
The recommended treatment for peripheral vascular disease prioritizes supervised exercise therapy as first-line intervention, combined with aggressive cardiovascular risk factor modification including statin therapy, antiplatelet therapy (aspirin or clopidogrel), and smoking cessation, with revascularization reserved only for patients who remain symptomatic after 3 months of optimal medical therapy and exercise. 1
Initial Management Framework
Supervised Exercise Therapy (First-Line Treatment)
- Supervised exercise training (SET) is the cornerstone of initial treatment for all symptomatic PAD patients 1
- Exercise sessions must be performed at least 3 times per week, for a minimum of 30-45 minutes per session, continuing for at least 12 weeks 1
- Walking should be the primary training modality, performed at high intensity (77-95% of maximal heart rate or 14-17 on Borg's scale) to maximize walking performance and cardiorespiratory fitness 1
- Patients should exercise to moderate-severe claudication pain levels, though improvements can occur with lesser pain severities 1
- When SET is unavailable, structured home-based exercise therapy (HBET) with monitoring through calls, logbooks, or connected devices should be implemented 1
- For patients undergoing endovascular revascularization, SET must be continued as adjuvant therapy 1
Cardiovascular Risk Factor Modification
Lipid Management:
- Statin therapy is mandatory for all PAD patients to reduce cardiovascular events and mortality 1
- Target LDL-cholesterol <100 mg/dL, with consideration of <70 mg/dL in very high-risk patients 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
- In high-risk patients with triglycerides >1.5 mmol/L despite lifestyle measures and statin therapy, icosapent ethyl 2g twice daily may be considered 1
- Fibrates are not recommended for cholesterol lowering 1
Diabetes Management:
- Tight glycemic control targeting HbA1c <7% (53 mmol/mol) is recommended to reduce microvascular complications 1
- SGLT2 inhibitors with proven cardiovascular benefit are recommended for patients with type 2 diabetes and PAD to reduce cardiovascular events 1
- GLP-1 receptor agonists with proven cardiovascular benefit are recommended for patients with type 2 diabetes and PAD to reduce cardiovascular events 1
- Hypoglycemia must be avoided 1
- Proper foot care is critical: daily foot inspection, appropriate footwear, chiropody/podiatric care, skin cleansing, and topical moisturizing creams, with urgent attention to any skin lesions or ulcerations 1
Smoking Cessation:
- All clinicians must advise patients to stop smoking at every encounter 1
- Comprehensive smoking cessation interventions should be offered, including behavior modification therapy, nicotine replacement therapy, or bupropion 1
Blood Pressure Control:
- Antihypertensive therapy targeting <140/90 mmHg in most patients, or <130/80 mmHg in those with diabetes or chronic kidney disease 3
- ACE inhibitors reduce cardiovascular morbidity and mortality in PAD patients regardless of hypertension status 4, 2
Antiplatelet Therapy
For Symptomatic PAD:
- Aspirin (75-160 mg daily) or clopidogrel (75 mg daily) monotherapy is recommended to reduce major adverse cardiovascular events (MACE) 1
- Clopidogrel is the preferred agent based on 23.8% relative risk reduction versus aspirin in PAD patients 1
- For patients with high ischemic risk and non-high bleeding risk, combination therapy with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily should be considered 1
- Long-term dual antiplatelet therapy (DAPT) is not recommended 1
- Oral anticoagulation monotherapy for PAD (unless indicated for another condition) is not recommended 1
For Asymptomatic PAD:
- Routine antiplatelet therapy is not recommended in asymptomatic PAD without clinically relevant atherosclerotic cardiovascular disease 1
- Aspirin (75-100 mg) for primary prevention may be considered in asymptomatic PAD patients with diabetes, absent contraindications 1
Pharmacological Therapy for Claudication Symptoms
Cilostazol (First-Line):
- Cilostazol 100 mg twice daily is recommended as effective therapy to improve symptoms and increase walking distance in patients with lifestyle-limiting claudication, in the absence of heart failure 1
- A therapeutic trial should be considered in all patients with lifestyle-limiting claudication 1
Pentoxifylline (Second-Line):
- Pentoxifylline 400 mg three times daily may be considered as second-line alternative to cilostazol 1
- Clinical effectiveness is marginal and not well established 1
- Patients on warfarin require more frequent prothrombin time monitoring when taking pentoxifylline 5
Not Recommended:
- L-arginine, propionyl-L-carnitine, and ginkgo biloba have not established effectiveness 1
- Chelation therapy (e.g., EDTA) is not indicated and may have harmful adverse effects 1
Revascularization Considerations
Timing and Indications
- After 3 months of optimal medical therapy (OMT) and exercise therapy, assess PAD-related quality of life 1
- Revascularization may be considered only in patients with impaired PAD-related quality of life despite 3 months of OMT and exercise therapy 1
- Revascularization is not recommended solely to prevent progression to chronic limb-threatening ischemia (CLTI) 1
- Revascularization is not recommended in asymptomatic PAD 1
Technical Approach
- Adapt the mode and type of revascularization to anatomical lesion location, lesion morphology, and general patient condition 1
- Endovascular intervention is the preferred technique for TASC type A iliac and femoropopliteal arterial lesions 1
- In femoropopliteal lesions, drug-eluting treatment should be considered as first-choice strategy 1
- Open surgical approach with autologous vein (e.g., great saphenous vein) should be considered for femoropopliteal lesions in low surgical risk patients when available 1
- Primary stent placement is not recommended in femoral, popliteal, or tibial arteries 1
- Stenting is effective as primary therapy for common and external iliac artery stenoses and occlusions 1
Follow-Up Protocol
- Regular follow-up at least once annually is mandatory 1
- Assess clinical and functional status, medication adherence, limb symptoms, and cardiovascular risk factors at each visit 1
- Perform duplex ultrasound assessment as needed 1
Critical Pitfalls to Avoid
- Never perform revascularization before completing 3 months of OMT and exercise therapy unless dealing with CLTI 1
- Do not use long-term DAPT routinely in PAD patients as bleeding risk outweighs benefits 1
- Avoid cilostazol in patients with heart failure as it is contraindicated 1
- Do not prescribe pentoxifylline as first-line therapy given marginal effectiveness 1
- Never use warfarin for PAD alone unless another indication exists (e.g., atrial fibrillation) 1