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Peripheral Arterial Occlusive Disease: Treatment & Medication
Updated: Oct 26, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Treatment of claudication is medical, with surgery reserved for severe cases.
- The goal of medical management is to impede the progression of peripheral arterial occlusive disease (PAOD).
- In patients who smoke, the most expedient way to impede the progress of PAOD is to stop tobacco use.
- Extensive evidence indicates that smoking cessation improves the prognosis.
- Improved walking distance and ankle pressure have been attributed to smoking cessation.
- Exercise plays a vital role in the treatment of claudication.
- Patients reduce their daily walking because of claudication pain and fear of further damage. This leads to an increasingly sedentary lifestyle that is even more detrimental.
- Regular walking programs result in substantial improvement in most patients with claudication. Improvements have ranged from 80-234% in controlled studies.
- A daily walking program of 45-60 minutes is recommended. The patient is instructed to walk until claudication pain occurs, rest until the pain subsides, and repeat the cycle.
- While the exact mechanism for improvement in walking distance with exercise remains unknown, regular exercise is thought to condition muscles to work more efficiently (more extraction of blood) and increase collateral vessel formation.
- Additional medical treatment includes control of the lipid profile, diabetes, and hypertension.
Surgical Care
Patients with limb-threatening ischemia or lifestyle-limiting claudication are referred to a vascular surgeon. Only then does evaluation warrant an arteriogram.
Consultations
See Surgical Care.
Medication
Daily aspirin is recommended for overall cardiovascular care. While standard dosages range from 81-325 mg/d, no consensus has been reached on the most effective dose.
Pentoxifylline (Trental) shows promise. Numerous randomized trials have documented modest improvements in walking distance when compared with placebo treatment groups. Treatment can take 2-3 months to produce noticeable results.
The use of clopidogrel bisulfate (Plavix) and enoxaparin sodium (Lovenox) in the treatment of this entity is increasing; however, further research is needed to establish clinical efficacy.
Cilostazol (Pletal) has recently shown increasing promise in the treatment of intermittent claudication. Several randomized studies have shown benefits in increasing walking distances for both the distance before the onset of claudication pain and the distance before exercise-limiting symptoms become intolerable (ie, maximal walking distance).In a randomized, double-blind, placebo-controlled trial, O’Donnell et al assessed the vascular and biochemical effects of cilostazol therapy in individuals (n=80) with peripheral arterial disease. Arterial compliance, transcutaneous oxygenation, ankle-brachial index, and treadmill walking distance were measured. The cilostazol group had significant reduction in the augmentation index and also showed reduction in transcutaneous oxygenation levels compared with the placebo group. Mean percentage change in walking distance improved more in the cilostazol group from baseline compared with the placebo group. Lipid profiles were also improved in the cilostazol group. The results showed that cilostazol is an efficacious treatment of peripheral arterial disease. In addition to improving patients’ symptoms and quality of life, cilostazol also appeared to have beneficial effects on arterial compliance.3
In 2009, Momsen et al evaluated the efficacy of drug therapy in improving walking distance in intermittent claudication.4 Their study determined that statins seemed to be the best in improving maximal walking distance.
Cholesterol-lowering statin agents are beneficial in the medical therapy for peripheral arterial disease.5 In addition to effectively lowering blood cholesterol profiles, recent evidence from the Heart Protection Study showed that cholesterol-lowering statin agents (simvastatin) reduced the rate of first major vascular events (myocardial infarction, stroke, or limb revascularization), with the largest benefits seen in patients with peripheral vascular disease.6
The benefits were demonstrated regardless of the baseline cholesterol profile. As such, cholesterol-lowering statin agents should be considered for medical treatment in patients with peripheral arterial disease.
Antiplatelet Agents
Decrease overall risk of cardiovascular disease from myocardial infarction and stroke. Also improve walking distance by enhancing circulation.
Aspirin (Anacin, Ascriptin, Bayer aspirin)
Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.
Adult
81-325 mg PO qd
Pediatric
Not established
Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Documented hypersensitivity; liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, and asthma; last 3 mo of pregnancy unless specifically directed by clinician; due to association of aspirin with Reye syndrome, do not use in children (<16 y) with flu
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants
Clopidogrel (Plavix)
Selectively inhibits ADP binding to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Indicated for reduction of atherosclerotic events.
Adult
75 mg PO qd
Pediatric
Not established
Potentiates effects of aspirin; potentiates anticoagulant effects of NSAIDs; may interfere with metabolism of phenytoin, tamoxifen, tolbutamide, warfarin, torsemide, and fluvastatin
Documented hypersensitivity; active pathological bleeding (eg, peptic ulcer, intracranial hemorrhage)
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause GI hemorrhage, abdominal pain, dyspepsia, gastritis, and constipation; small prevalence of neutropenia
Cilostazol (Pletal)
Mechanism of effects on symptoms of intermittent claudication not fully understood. Cilostazol and several of its metabolites are PDE III inhibitors, inhibiting phosphodiesterase activity and suppressing cAMP degradation, with a resultant increase in cAMP in platelets and blood vessels, leading to inhibition of platelet aggregation and vasodilation, respectively. Reversibly inhibits platelet aggregation induced by various stimuli, including thrombin, ADP, collagen, arachidonic acid, epinephrine, and shear stress.
Adult
100 mg PO bid at least 30 min before or 2 h after breakfast and dinner; consider 50 mg bid if coadministered with inhibitors of CYP3A4 (eg, ketoconazole, itraconazole, erythromycin, diltiazem) or with inhibitors of CYP2C19 (eg, omeprazole)
Pediatric
Not established
Diltiazem, erythromycin, grapefruit juice, itraconazole, ketoconazole, macrolide antibiotics, and omeprazole may increase levels
Cilostazol and several of its metabolites are PDE III inhibitors; several drugs with this pharmacologic effect have caused decreased survival compared with placebo in patients with class III-IV congestive heart failure; contraindicated in patients with congestive heart failure of any severity and in those with known or possible hypersensitivity to any of its components; also contraindicated with grapefruit juice coadministration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment; do not prescribe or administer without thoroughly reading complete prescribing information
Pentoxifylline (Trental)
Indicated for treatment of patients with intermittent claudication due to atherosclerosis or other obstructive arteriopathies. Improves blood flow by increasing red blood cell deformability, which decreases viscosity of blood.
Adult
400 mg PO tid
Pediatric
Not established
Coadministration with cimetidine or theophylline increases effect and toxic potential; increases effect of antihypertensives
Documented hypersensitivity; cerebral or retinal hemorrhage
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment; patients on anticoagulant therapy may require close monitoring; caution in patients with intolerance to caffeine, theophylline, or theobromine
Antilipemic Agents
These agents are beneficial in lowering blood cholesterol profiles, which may reduce the rate of first major vascular events.
Simvastatin (Zocor)
Reduces cardiovascular heart disease mortality and morbidity (eg, nonfatal myocardial infarction or stroke, revascularization procedures) in high-risk patients (ie, existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease). Competitively inhibits HMG-CoA, which catalyzes the rate-limiting step in cholesterol synthesis. Patients should be placed on a cholesterol-lowering diet; the diet should be continued indefinitely.
Adult
40 mg PO hs if renal insufficiency not severe
5 mg PO hs in patients with severe renal insufficiency; not to exceed 10 mg/d when coadministered with fibrates (eg, gemfibrozil), niacin (>1 g/d), or cyclosporine; not to exceed 20 mg/d when coadministered with verapamil or amiodarone
Pediatric
Not established
Effects increase with cholestyramine; increases toxicity of gemfibrozil, clofibrate, niacin, cyclosporine, and oral anticoagulants; itraconazole and ketoconazole increase toxicity of lovastatin; concurrent use with erythromycin may increase risk of rhabdomyolysis; when coadministered with fibrates (eg, gemfibrozil), niacin (>1 g/d), or cyclosporine do not exceed 10 mg/d; when coadministered with verapamil or amiodarone do not exceed 20 mg/d
Documented hypersensitivity; active liver disease; unexplained elevation of liver enzymes
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Initiate treatment at lower dose with severe renal insufficiency and discontinue if renal function worsens; discontinue therapy if symptoms of myopathy develop; caution in history of liver disease and those who consume excessive amounts of alcohol
More on Peripheral Arterial Occlusive Disease |
| Overview: Peripheral Arterial Occlusive Disease |
| Differential Diagnoses & Workup: Peripheral Arterial Occlusive Disease |
 Treatment & Medication: Peripheral Arterial Occlusive Disease |
| Follow-up: Peripheral Arterial Occlusive Disease |
| Multimedia: Peripheral Arterial Occlusive Disease |
| References |
| « Previous Page | Next Page » |
References
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Momsen AH, Jensen MB, Norager CB, Madsen MR, Vestersgaard-Andersen T, Lindholt JS. Drug therapy for improving walking distance in intermittent claudication: a systematic review and meta-analysis of robust randomised controlled studies. Eur J Vasc Endovasc Surg. Oct 2009;38(4):463-74. [Medline].
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Further Reading
Keywords
peripheral arterial occlusive disease, PAOD, chronic arterial insufficiency, lower extremity claudication, lower extremity ischemia, lower-extremity claudication, lower-extremity ischemia, peripheral vascular disease, cholesterol, smoking, hypertension
