Peripheral Vascular Disease Management

Aka: Peripheral Vascular Disease Management, Claudication Management, Peripheral Arterial Disease Management

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II. Background

  1. Claudication is very disabling
  2. Consider intensive management in all patients

III. Protocol: Overall (See agents below)

  1. Ankle-Brachial Index < 0.3
    1. Treat as Limb Threatening Ischemia (emergent surgical management)
  2. Ankle-Brachial Index 0.3 to 1.0
    1. Step 1: Risk factor modification for 3 months
      1. See General measures below
      2. Aspirin 81 to 325 mg orally daily (or Plavix 75 mg daily)
    2. Step 2: No change in 3 months after step 1
      1. Add Cilostazol (Pletal) to regimen for 3 months
        1. High side effect profile (Dizziness, GI symptoms)
        2. Avoid Pletal in Congestive Heart Failure
        3. Pletal 100 mg twice daily (50 mg twice daily if also on Calcium Channel Blocker)
    3. Step 3: No change in 3 months after step 2
      1. Evaluate for possible surgery (see below)
  3. Ankle-Brachial Index >1.0
    1. Consider alternative diagnosis
    2. See Leg Pain for differential diagnosis
  4. References
    1. (1996) Lancet 348:1329-39 [PubMed]

IV. Protocol: Evaluation for surgical intervention

  1. Indications
    1. Significant limitations refractory to other measures
    2. Limb-threatening ischemia (usually ABI <0.3)
      1. Gangrene
      2. Non-healing ulcers
      3. Rest pain
  2. Non-invasive Testing
    1. Ankle-Brachial Index (Non-specific screening)
    2. Segmental Arterial Pressure (Defines Occlusion site)
    3. Treadmill Testing
      1. Perform at 2 MPH at 12% grade
      2. Reassuring test: Patient walks >5 minutes
      3. Signs of significant Occlusion
        1. Drop in ankle systolic BP with Exercise
        2. Claudication limits walking to <5 minutes
    4. Duplex arterial Ultrasound
      1. Significant if Occlusion >50%
      2. Excellent noninvasive confirmatory test
        1. Helps to define surgical candidates
        2. Assists to risk stratify for arteriography

V. Management: General Measures for risk modification

  1. Cardiovascular Risk Reduction is critical
    1. Carries same risk as Coronary Artery Disease
  2. Antiplatelet Therapy (Aspirin, Clopidogrel)
    1. See below
  3. Phosphodiesterase Inhibitor (Cilostazol)
    1. See below
  4. Tobacco Cessation is the most important intervention
    1. Tobacco Cessation increases walking time by 6.5 minutes on average
  5. Exercise Program (see below)
    1. Specific protocol is required
    2. Unstructured programs (e.g. "walk more") are not typically effective
  6. Maximize Diabetes Mellitus management (Hgb A1C <7%)
  7. Maximize Hyperlipidemia Management (LDL <100 mg/dl)
    1. Statin Medications (e.g. Simvastatin, Atorvastatin, Rosuvastatin) at high intensity dosing
    2. Reduced need for revascularization, amputation and improves pain-free walk distance
    3. Kumbhani (2014) Eur Heart J 35(41): 2864-72 [PubMed]
    4. McDermott (2003) Circulation 107(5): 757-61 [PubMed]
  8. Maximize Hypertension Management (<130/80 mmHg)
    1. ACE Inhibitors may be preferred agents in PVD
    2. Ramapril 10 mg daily increased walk time an extra 4 minutes over 6 months
    3. Ahimastos (2013) JAMA 309(5): 453-60 [PubMed]
    4. Yusuf (2000) N Engl J Med 342:145-53 [PubMed]
  9. Direct Oral Anticoagulant (DOAC, e.g. Xarelto) may be considered in some patients
    1. Studied in combination with low dose Aspirin (81 mg) with use over 2 years
    2. May reduce major cardiovascular events (1 in 50) and amputations (1 in 150)
    3. However, risk of major bleeding events (1 in 100)
    4. (2019) presc lett 26(7): 38

VI. Management: Antiplatelet Medications

  1. Antiplatelet Medications
    1. Indications
      1. Antiplatelet agents do not decrease Claudication symptoms
      2. Antiplatelet agents reduce the risk of PAD associated Acute Coronary Syndrome and Cerebrovascular Accident
      3. Single antiplatelet agent (e.g. Aspirin, Clopidogrel) is sufficient
        1. Reserve Dual Antiplatelet Therapy for the immediate post-revascularization period
    2. First-Line agents
      1. Aspirin 75 to 150 mg orally daily
    3. Second-Line (alternatives if Aspirin intolerant)
      1. Clopidogrel (Plavix)
      2. Ticlopidine (Ticlid)
  2. Phosphodiesterase Inhibitor medications
    1. Cilostazol (Pletal)
      1. Reserved for symptomatic PAD patients refractory to Exercise and optimized Cardiovascular Risks
      2. Significant benefits in Claudication walk distance
      3. Preferred agent over Pentoxifylline
      4. Higher frequency of adverse effects (e.g. Headache, Diarrhea, Dizziness, Palpitations)
      5. Contraindicated in Congestive Heart Failure
      6. Thompson (2002) Am J Cardiol 90:1314-9 [PubMed]
      7. Brown (2021) Cochrane Database Syst Rev (6):CD003748 [PubMed]
    2. Pentoxifylline (Trental)
      1. Not recommended due to low efficacy, three times daily dosing and gastrointestinal adverse effects
      2. Theoretically increases RBC deformity for the purpose of improving flow
      3. Only small benefits in Claudication distance
      4. Listed for historical purposes only, but if used, effects may not be evident for 3 months
  3. Anticoagulation (e.g. Rivaroxiban)
    1. Indications
      1. Consider in CAD patients with symptomatic PAD
    2. Rivaroxiban (Xarelto) 2.5 mg twice daily (in combination with Aspirin)
      1. Reduced cardiac associated major events, but not FDA approved for this indication
      2. NNT 50 to prevent one cardiovascular event (e.g. MI, cardiac death) in PAD patients (over 2 years)
      3. NNT 150 to prevent one Limb Amputation in PAD (over 2 years)
      4. NNH 100 to cause one major bleeding complication (over 2 years)
      5. Anand (2018) Lancet 391(10117):219-29 [PubMed]
      6. (2024) presc lett 31(8): 43-4

VII. Management: Exercise

  1. Exercise Stress Test needed before vigorous activity
    1. Peripheral Arterial Disease is a marker for Coronary Artery Disease
  2. Efficacy
    1. Walking improves Claudication distance
      1. Average increase in walk distance of 5 minutes and 113 meters
      2. Benefits are sustained for more than 2 years
      3. Watson (2008) Cochrane Database Syst Rev 8(4): CD000990 [PubMed]
    2. Effects are equivalent to percutaneous Angioplasty in walk distance and quality of life
      1. Frans (2012) Br J Surg 99(1): 16-28 [PubMed]
  3. Exercise types
    1. Walking (standard walking or on a treadmill)
    2. Stair stepping
  4. Time for Exercise
    1. Start: 3-5 times per week for 30 minutes per time
    2. Increase by 5 minutes until 50 minutes/session
    3. Continue program for at least 6 months
      1. Supervised Exercise program has highest efficacy
  5. Speed and grade selection
    1. Intensity that provokes Claudication at 3-5 minutes
    2. Continue to increase intensity as ability improves
      1. Claudication should occur at every session
  6. Intermittent walking technique
    1. Walk until moderate to near maximal Claudication pain
    2. Rest briefly at severe Claudication symptoms
    3. Rest in sitting or standing position
    4. Restart walking when Claudication symptoms tolerable
  7. References
    1. Stewart (2002) N Engl J Med 347:1941-51 [PubMed]

VIII. Management: Surgical

  1. Indications
    1. Failed maximal medical therapy (see above)
    2. Severe symptoms significantly reducing life quality
    3. Critical Limb Ischemia (surgical emergency)
      1. Ischemic Rest pain >2 weeks OR
      2. Non-healing ischemic wounds or tissue loss OR
      3. Gangrene in one or both legs
  2. Lesion localization
    1. Arterial duplex Ultrasound
    2. CT Angiography
    3. Magnetic resonance anigiography
    4. Angiography
  3. Procedures
    1. Endovascular Revascularization or Angioplasty (with or without stent placement)
      1. Higher risk of restenosis
        1. Brachytherapy reduces restenosis risk
      2. Significantly lower risk of complications than arterial bypass graft
      3. High efficacy in aorto-illiac (90% at five years)
      4. Low efficacy femoral-popliteal (<60% at five years)
    2. Arterial Bypass Graft
      1. High efficacy in aorto-illiac (90% at 5 years)
      2. Mod. efficacy femoral-popliteal (70-85% at 5 years)
      3. Higher rate of mortality (<3%)
    3. Intra-arterial Directed Thrombolysis (e.g. Urokinase)
    4. Endarterectomy

IX. References

  1. Boccalon (1999) Drugs Aging 14:247
  2. Samuelson (March, 2000) Fed Pract, p. 34-50
  3. Carman (2000) Am Fam Physician 61(4):1027-32 [PubMed]
  4. Firnhaber (2019) Am Fam Physician 99(6): 362-9 [PubMed]
  5. Firnhaber (2022) Am Fam Physician 105(1): 65-72 [PubMed]
  6. Gardner (1995) JAMA 274(12):975-80 [PubMed]
  7. Gey (2004) Am Fam Physician 69:525-33 [PubMed]
  8. Hirsch (2001) JAMA 286(11):1317-24 [PubMed]
  9. Santilli (1999) Am Fam Physician 59(7):1899-908 [PubMed]
  10. Santilli (1996) Am Fam Physician 53(4):1245-53 [PubMed]
  11. (1999) Med Lett Drugs Ther 41:(1052):44-6 [PubMed]

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