Peripheral arterial disease medical therapy

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AHA/ACC Guidelines on Management of Lower Extremity PAD
Guidelines for Clinical Assessment of Lower Extremity PAD
Guidelines for Diagnostic Testing for suspected PAD
Guidelines for Screening for Atherosclerotic Disease in Other Vascular Beds in patients with Lower Extremity PAD
Guidelines for Medical Therapy for Lower Extremity PAD
Guidelines for Structured Exercise Therapy for Lower Extremity PAD
Guidelines for Minimizing Tissue Loss in Lower Extremity PAD
Guidelines for Revascularization of Claudication in Lower Extremity PAD
Guidelines for Management of CLI in Lower Extremity PAD
Guidelines for Management of Acute Limb Ischemial in Lower Extremity PAD
Guidelines for Longitudinal Follow-up for Lower Extremity PAD
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Aarti Narayan, M.B.B.S [3]; Vishnu Vardhan Serla M.B.B.S. [4]

Overview

Despite its prevalence and cardiovascular risk implications, only 25 percent of patients with peripheral arterial disease are actively being treated. The medical therapy aims to reduce the atherosclerotic risk factors which include diabetes mellitus, hypertension, dyslipidemia and smoking, to improve walking time and distance and to prevent the progression of the peripheral arterial disease and the need of invasive surgical procedures. All patients with peripheral arterial disease should be prescribed an antiplatelet agent.

Medical Therapy

Medical Therapy for Intermittent Claudication

Reduction in Modifiable Cardiovascular Risk Factors

• Diabetes control
• Hypertension treatment
• Dyslipidemia treatment
• Smoking cessation

Improvement of the Walking Ability

Exercise Rehabilitation

• A regular walking program four times a week for six month results in an average of 6.5 minutes improvement in the walking time.
• It opens up collateral circulation.
• It reduces cardiovascular mortality.
• It improves quality of life.

Cilostazol

• Cilostazol is a phosphodiesterase III inhibitor.
• It is FDA approved.
• Cilostazol is not administered to all PAD cases but rather to selected cases where regular walking program has failed to improve the walking time and capacity.
• It is contraindicated in congestive heart failure.
• Side effects:
  • Headache
  • Diarrhea
  • Gastric upset
  • Palpitations
  • Dizziness

Pentoxifylline

• It reduces platelets aggregation and improves the flexibility of red blood cell membranes.
• It is FDA approved.

Propionyl-l-carnitine

• The overall benefit is not well established and this medication is under investigation.

Statins

• Statins improve symptoms of intermittent claudication.
• They may decrease the incidence of coronary artery disease and cerebrovascular disease.
• They increase survival.
• Statins are still under investigation.

Angiotensin Converting Enzyme Inhibitors

• They decrease the risk of ischemic cardiovascular events.

Other Drugs Under Investigation

• Rosiglitazone
• L-Arginine
• Prostaglandins
• Angiogenic Factors: VEGF, bFGF

Antiplatelet and Anticoagulant Therapy

• Antiplatelet therapy is indicated for all patients with PAD unless contraindicated for a compelling reason.

Aspirin

• It decreases the need for surgical intervention and limb loss.
• It decreases cardiovascular and cerebrovascular risks.
• It decreases vascular events and appears to prevent peripheral arterial occlusion after revascularization procedures.

Clopidogrel

• It has shown to be superior to aspirin in the prevention of atherosclerotic vascular events.

Dual Antiplatelet Therapy

• According to CHARISMA study, aspirin and clopidogrel combined together are superior to the use of each of the drugs alone.

Anticoagulants

• Warfarin was not proven to be effective in the treatment of PAD.

Shown below is a table depicting the different therapeutic choices, their benefits and limitations:

Intervention	Benefits on treadmill/QoL	Limitations	PAD Cohort Indicated
Exercise	100% Improved	Availability and motivation	50% - 85%
Cilostazol	50% Improved	CHF, Medication adverse effects	50% - 85%
Angioplasty	Improvement	Proximal arteries best	10% - 15%
Surgery	150% Improved	Graft failure, high morbidity and mortality	< 5%

The moderate consumption of alcohol has been found to be associated with a reduction of the risk of PVD by almost one-third compared to those who do not drink alcohol.

Medical Therapy for Critical Limb Ischemia

• Patients with critical limb ischemia must be planned for endovascular or surgical intervention; nevertheless, they also need medical therapy similar to that of patients with claudication, aiming at:
  • Reducing the atherosclerotic risk factors
  • Improving exercise tolerance
  • Preventing progression and re-occurrence of symptomatic PAD lesions through treatment with antiplatelets
• In addition, patients presenting with severe ulcers and evidence of infections should be administered systemic antibiotics and should be received an appropriate wound care.

Medical Therapy for Acute Occlusion

• Urgent measures should be taken to ensure blood flow and protect the limb:
  • ICU admission
  • Administration of heparin for anticoagulation
  • Electrolytes, acid- base and renal status monitoring
  • Limb status monitoring and frequent assessment of the need for fasciotomy.

• If the limb is not immediately threatened:
  • Continue treatment with thrombolytic therapy for 14 days.
• If the limb ischemia is critical:
  • Consider percutaneous transluminal angioplasty
  • Consider surgery: thromboembolectomy, bypass grafting
• Send sample for pathologic examination (myxoma may be present)

Contraindicated medications

Severe peripheral arterial disease is considered an absolute contraindication to the use of the following medications:

• Almotriptan
• Eletriptan
• Metoprolol
• Frovatriptan
• Rizatriptan
• Isometheptene mucate, dichloralphenazone and acetaminophen
• Sumatriptan
• Zolmitriptan

2011 and 2005 ACCF/AHA Guidelines for the Management of Patients With Peripheral Artery Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) (DO NOT EDIT)

Antiplatelet and Antithrombotic Drugs (DO NOT EDIT)

Class I

"1. Antiplatelet therapy is indicated to reduce the risk of MI, stroke, and vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia. (Level of Evidence: A) "

"2. Aspirin, typically in daily doses of 75 to 325 mg, is recommended as safe and effective antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia.(Level of Evidence: B) (changed from A to B)"

"3. Clopidogrel (75 mg per day) is recommended as a safe and effective alternative antiplatelet therapy to aspirin to reduce the risk of MI, ischemic stroke, or vascular death in individuals with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia. (Level of Evidence: B)"

Class III (No Benefit)

"1. In the absence of any other proven indication for warfarin, its addition to antiplatelet therapy to reduce the risk of adverse cardiovascular ischemic events in individuals with atherosclerotic lower extremity PAD is of no benefit and is potentially harmful due to increased risk of major bleeding. (Level of Evidence: B)(changed from C to B)"

Class IIa

"1. Antiplatelet therapy can be useful to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with an ABI less than or equal to 0.90. (Level of Evidence: C)"

Class IIb

"1. The usefulness of antiplatelet therapy to reduce the risk of MI, stroke, or vascular death in asymptomatic individuals with borderline abnormal ABI, defined as 0.91 to 0.99, is not well established. (Level of Evidence: A)"

"2. The combination of aspirin and clopidogrel may be considered to reduce the risk of cardiovascular events in patients with symptomatic atherosclerotic lower extremity PAD, including those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization (endovascular or surgical), or prior amputation for lower extremity ischemia and who are not at increased risk of bleeding and who are at high perceived cardiovascular risk. (Level of Evidence: B)"

Medical and Pharmacological Treatment for Chronic Limb Ischemia (DO NOT EDIT)

Class III

"1. Parenteral administration of pentoxifylline is not useful for the treatment of CLI. (Level of Evidence: B)"

Thrombolysis for Acute and Chronic Limb Ischemia (DO NOT EDIT)

Class I

"1. Catheter-based thrombolysis is an effective and beneficial therapy and is indicated for patients with acute limb ischemia (Rutherford categories I and IIa) of less than 14 days’ duration. (Level of Evidence: A)"

Class IIa

"1. Mechanical thrombectomy devices can be used as adjunctive therapy for acute limb ischemia due to peripheral arterial occlusion. (Level of Evidence: B)"

Class IIb

"1. Catheter-based thrombolysis or thrombectomy may be considered for patients with acute limb ischemia (Rutherford category IIb) of more than 14 days’ duration.(Level of Evidence: B)"

Prostaglandins use in Chronic Limb Ischemia (DO NOT EDIT)

Class III

"1. Oral iloprost is not an effective therapy to reduce the risk of amputation or death in patients with CLI. (Level of Evidence: B)"

Class IIb

"1. Parenteral administration of PGE-1 or iloprost for 7 to 28 days may be considered to reduce ischemic pain and facilitate ulcer healing in patients with CLI, but its efficacy is likely to be limited to a small percentage of patients. (Level of Evidence: A)"

Angiogenic Growth Factors use in Chronic Limb Ischemia (DO NOT EDIT)

Class IIb

"1. The efficacy of angiogenic growth factor therapy for treatment of CLI is not well established and is best investigated in the context of a placebo-controlled trial. (Level of Evidence: C)"

Lipid-Lowering Drugs (DO NOT EDIT)

Class I

"1. Treatment with a hydroxymethyl glutaryl-coenzyme A reductase inhibitors (statin) medication is indicated for all patients with PAD to achieve a target LDL cholesterol level of less than 100 mg per dL.(Level of Evidence: B)"

Class IIa

"1. Treatment with an HMG coenzyme-A reductase inhibitor (statin) medication to achieve a target LDL cholesterol level of less than 70 mg per dL is reasonable for patients with lower extremity PAD at very high risk of ischemic events. (Level of Evidence: B)"

"2. Treatment with a fibric acid derivative can be useful for patients with PAD and low HDL cholesterol, normal LDL cholesterol, and elevated triglycerides. (Level of Evidence: C)"

Antihypertensive Drugs (DO NOT EDIT)

Class I

"1. Antihypertensive therapy should be administered to hypertensive patients with lower extremity PAD to achieve a goal of less than 140 mm Hg systolic over 90 mm Hg diastolic (nondiabetics) or less than 130 mm Hg systolic over 80 mm Hg diastolic (diabetics and individuals with chronic renal disease) to reduce the risk of MI, stroke, congestive heart failure, and cardiovascular death. (Level of Evidence: A). "

"2. Beta-adrenergic blocking drugs are effective antihypertensive agents and are not contraindicated in patients with PAD. (Level of Evidence: A). "

Class IIa

"1. The use of angiotensin-converting enzyme inhibitors is reasonable for symptomatic patients with lower extremity PAD to reduce the risk of adverse cardiovascular events. (Level of Evidence: B). "

Class IIb

"1. Angiotensin-converting enzyme inhibitors may be considered for patients with asymptomatic lower extremity PAD to reduce the risk of adverse cardiovascular events. (Level of Evidence: C). "

Diabetes Therapies (DO NOT EDIT)

Class I

"1. Proper foot care, including use of appropriate footwear, chiropody/podiatric medicine, daily foot inspection, skin cleansing, and use of topical moisturizing creams, should be encouraged and skin lesions and ulcerations should be addressed urgently in all diabetic patients with lower extremity PAD. (Level of Evidence: B)"

Class IIa

"1. Treatment of diabetes in individuals with lower extremity PAD by administration of glucose control therapies to reduce the hemoglobin A1c to less than 7% can be effective to reduce microvascular complications and potentially improve cardiovascular outcomes. (Level of Evidence: C)"

Homocysteine-Lowering Drugs in PAD Patients (DO NOT EDIT)

Class IIb

"1. The effectiveness of the therapeutic use of folic acid and B12 vitamin supplements in individuals with lower extremity PAD and homocysteine levels greater than 14 micromoles per liter is not well established. (Level of Evidence: C)"

Exercise and Lower Extremity PAD Rehabilitation (DO NOT EDIT)

Class I

"1. A program of supervised exercise training is recommended as an initial treatment modality for patients with intermittent claudication. (Level of Evidence: A). "

"2. Supervised exercise training should be performed for a minimum of 30 to 45 minutes, in sessions performed at least 3 times per week for a minimum of 12 weeks. (Level of Evidence: A). "

Class IIb

"1. The usefulness of unsupervised exercise programs is not well established as an effective initial treatment modality for patients with intermittent claudication. (Level of Evidence: B). "

Cilostazol use in Claudication (DO NOT EDIT)

Class I

"1. Cilostazol (100 mg orally 2 times per day) is indicated as an effective therapy to improve symptoms and increase walking distance in patients with lower extremity PAD and intermittent claudication (in the absence of heart failure). (Level of Evidence: A). "

"2. A therapeutic trial of cilostazol should be considered in all patients with lifestyle-limiting claudication (in the absence of heart failure). (Level of Evidence: A). "

Pentoxifylline use in Claudication (DO NOT EDIT)

Class IIb

"1. Pentoxifylline (400 mg 3 times per day) may be considered as second-line alternative therapy to cilostazol to improve walking distance in patients with intermittent claudication. (Level of Evidence: A)"

"2. The clinical effectiveness of pentoxifylline as therapy for claudication is marginal and not well established. (Level of Evidence: C)"

Other Proposed Medical Therapies in Claudication (DO NOT EDIT)

Class III

"1. Oral vasodilator prostaglandins such as beraprost and iloprost are not effective medications to improve walking distance in patients with intermittent claudication. (Level of Evidence: A). "

"2. Vitamin E is not recommended as a treatment for patients with intermittent claudication. (Level of Evidence: C). "

"3. Chelation (e.g., ethylenediaminetetraacetic acid) is not indicated for treatment of intermittent claudication and may have harmful adverse effects. (Level of Evidence: A). "

Class IIb

"1. The effectiveness of L-arginine for patients with intermittent claudication is not well established. (Level of Evidence: B)"

"2. The effectiveness of propionyl-L-carnitine as a therapy to improve walking distance in patients with intermittent claudication is not well established. (Level of Evidence: B)"

"3. The effectiveness of ginkgo biloba to improve walking distance for patients with intermittent claudication is marginal and not well established. (Level of Evidence: B)"

Antimicrobial Regimen

Ulcerated Skin: Venous/Arterial Insufficiency; Pressure With Secondary Infection (Infected Decubiti) Treatment

• Ulcerated skin: venous/arterial insufficiency; pressure with secondary infection (infected decubiti) treatment

• Preferred regimen (1): Imipenem 0.5 g IV q6h (OR Meropenem 1 g IV q24h OR Doripenem 500 mg IV q8h)
• Preferred regimen (2): Ticarcillin-Clavulanate 3.1 g IV q8h
• Preferred regimen (3): Piperacillin-Tazobactam 3.375 g IV q6h
• Preferred regimen (4): Ertapenem 1 g IV q24h
• Alternative regimen (1): Ciprofloxacin 500 mg PO bid OR Levofloxacin PO 500 mg qd AND Metronidazole 500 mg PO qid
• Alternative regimen (2): Cefepime 2 g IV q12h OR Ceftazidime 2 g IV q8h AND Metronidazole 500 mg PO qid
• Note (1): If gram positive cocci on gram stain add Vancomycin.
• Note (2): If the ulcer is inflamed, treat with parenteral antibiotics with no topical treatment.
• Note (3): If the ulcer is not clinically inflamed, consider debridement, removal of foreign body, reduce the pressure for weight bearing limbs and leg elevation.
• Note (4): If not inflamed, healing improved on air bed, protein supplement, radiant heat and electric stimulation.
• Note (5): Avoid chlorhexidine and povidone iodine as it may harm the granulation tissue.

See also

• Venous ulcer
• Bedsore

References

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