Peripheral Arterial Occlusive Disease Treatment & Management

Treatment of claudication is medical, ^[13] except in severe cases. The goal of medical management of peripheral arterial occlusive disease (PAOD) is to impede the progression of the disease. This may include both pharmacologic and nonpharmacologic measures. For patients in whom medical and exercise therapy fail or those who have lifestyle-limiting claudication symptoms, surgical treatment options are the next line of therapy.

In July 2014, the Society for Cardiac Angiography and Interventions (SCAI) issued a consensus statement on the treatment of infrapopliteal arterial disease. The statement indicated the following ^[14] :

• Endovascular intervention is not appropriate for most single-vessel, mildly symptomatic, or asymptomatic blockages of infrapopliteal vessels
• It is not appropriate to treat most cases of moderate-to-severe claudication or major tissue loss in one-vessel disease and mild claudication in one-, two-, or three-vessel disease
• Primary amputation should be the preferred intervention in nonambulatory patients with a limited life expectancy and extensive necrosis or gangrene
• Consider surgical bypass and evaluate its associated risks for ambulatory patients with a patent infrapopliteal artery that has direct flow to the foot and an adequate autologous venous conduit
• Use balloon angioplasty for clinically significant infrapopliteal arterial disease; consider bailout bare-metal and drug-elutive stents for tibial arterial disease that is refractory to treatment with balloon angioplasty

Moreover, the SCAI indicated that intervention for infrapopliteal disease is appropriate in patients with two- or three-vessel disease and (1) moderate-to-severe claudication with a focal arterial lesion; (2) ischemic foot pain during rest (Rutherford classification 4); or (3) minor and major (skin necrosis, gangrene) tissue loss. ^[14]

Guidelines for the management of various aspects of PAOD have been published by the Society for Vascular Surgery (SVS) ^[15] ; the American Heart Association (AHA) and the American College of Cardiology (ACC) ^[16] ; the European Society of Cardiology (ESC), in collaboration with the European Society for Vascular Surgery (ESVS) ^[17] ; the SVS and the ESVS with the World Federation of Vascular Societies (WFVS) ^[18] ; the Canadian Cardiovascular Society (CCS) ^[19] ; and Diabetes Feet Australia (DFA). ^[20]  (See Guidelines.)

Misdiagnosis for intermittent claudication rarely leads directly to limb loss. However, it is advisable to make early referrals to a vascular surgeon so as to reduce the likelihood of any legal action.

In patients who smoke, the most expedient way of impeding the progression of PAOD is to stop tobacco use. Extensive evidence indicates that smoking cessation improves the prognosis. In addition, improved walking distance and ankle pressure have been attributed to smoking cessation.

Daily aspirin has been recommended for overall cardiovascular care. Standard dosages range from 81 to 325 mg/day, but no consensus has been reached on the most effective dose.

As noted in SVS guidelines for management of claudication, ^[15] numerous randomized trials have documented modest improvements in walking distance in pentoxifylline treatment groups as compared with placebo treatment groups. Treatment may take as long as 2-3 months to produce noticeable results.

The use of clopidogrel bisulfate and enoxaparin sodium in the treatment of PAOD is increasing; however, further research is needed to establish clinical efficacy.

Several randomized studies have found cilostaxol to have a beneficial effect on walking distances, ^[15] increasing both the distance before the onset of claudication pain and the distance before exercise-limiting symptoms become intolerable (ie, the maximal walking distance).

In a randomized, double-blind, placebo-controlled trial, O’Donnell et al assessed the vascular and biochemical effects of cilostazol therapy on 80 patients with peripheral arterial disease, finding that this agent to be an efficacious treatment that, besides improving patients’ symptoms and quality of life, appeared to have beneficial effects on arterial compliance. ^[21]

The investigators in this study measured arterial compliance, transcutaneous oxygenation, ankle-brachial index (ABI), and treadmill walking distance. ^[21] As compared with the placebo group, the cilostazol group had significant reduction in the augmentation index and also showed reduction in transcutaneous oxygenation levels. The mean percentage change in walking distance from baseline was greater in the cilostazol group than in the placebo group. Lipid profiles were also improved in the cilostazol group.

In 2009, Momsen et al evaluated the efficacy of drug therapy for improving walking distances in intermittent claudication. ^[22] Their study determined that statins seemed to be the best at improving maximal walking distance.

Evidence from the Heart Protection Study indicated that cholesterol-lowering statin agents (simvastatin), besides effectively lowering blood cholesterol profiles, reduced the rate of first major vascular events (myocardial infarction [MI], stroke, or limb revascularization), with the largest benefits seen in patients with peripheral vascular disease. ^[23] The benefits were demonstrated regardless of the baseline cholesterol profile.

These results suggest that cholesterol-lowering statin agents should be considered for medical treatment in patients with peripheral arterial disease. Such agents appear to provide substantial benefit for individuals with PAOD. ^[24]

Additional medical treatment may include control of diabetes as appropriate. For example, insulin-sensitizing medication may reduce PAOD in type 2 diabetics with coronary disease. ^[25]

In a secondary analysis of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, of 303 patients with type 2 diabetes and stable coronary disease without peripheral arterial disease (PAD) at baseline, those treated with insulin-sensitizing therapy (16.9%) (ie, metformin or a glitazone) were less likely to develop any type of new PAD during 4.6 years of follow-up than were patients treated with insulin-providing therapy (24.1%). ^[25]

In the study, patients who received insulin-sensitizing therapy had lower frequencies of lower-extremity revascularization (1.1% vs 2.6%), low ankle-brachial index (16.5% vs 22.7%), and amputation (0.1% vs 1.6%) than patients who received insulin-providing therapy. ^[25] These findings suggest that progression of system-wide atherosclerosis, and thus development of PAD, in diabetic individuals with relatively advanced coronary disease may be slowed or reduced with insulin-sensitizing medication.

Surgical treatment options, typically reserved for patients with more severe disease or those in whom nonsurgical management fails, include the following:

• Open bypass surgery
• Endovascular therapy (eg, stenting, balloon angioplasty, or atherectomy)

Whereas open surgery dominated the treatment options two decades ago, endovascular management of PAOD has become exponentially more popular since then (see the image below). ^[26]

Peripheral arterial occlusive disease. Procedures performed during acute admission for peripheral arterial disease in US from 1996 to 2005. Reprinted from Journal of Vascular Surgery, Vol 49(4), Rowe VL et al, Patterns of treatment for peripheral arterial disease in the United States: 1996-2005, Pages 910-7, Apr 2009, with permission from Elsevier.

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Along with the proliferation of endovascular procedures, a development of particular note has been the concurrent decrease in amputation rates for patients with PAOD. Unfortunately, factors directly contributing to lower amputation rates are difficult to delineate; they probably involve some combination of improved disease screening and patient awareness, better medical therapy, and evolving surgical device and technical modalities.

A few studies have directly compared endovascular and open surgical treatment options for patients with symptomatic PAOD. Unfortunately, a meta-analysis of four randomized control trials and six observational studies was unable to establish any well-defined superiority for either approach. Overall, recommendations for selecting a treatment modality may depend on the patient’s life expectancy and comorbid conditions, as well as on the extent of the occlusive disease. ^[27]

In October 2014, the US Food and Drug Administration (FDA) approved the first drug-coated balloon (DCB) for the treatment of peripheral arterial vascular disease, the Lutonix 035 Drug Coated Balloon Percutaneous Transluminal Angioplasty Catheter (Lutonix, New Hope, MN). The device is coated with paclitaxel and intended for use to treat stenotic or obstructive lesions in the femoropopliteal arteries to improve limb perfusion. Similar devices that have been developed include In.Pact Admiral (Medtronic Vascular, Santa Rosa, CA) and Stellarex (Spectranetics, Colorado Springs, CO).

In August 2019, the FDA issued an updated notification to healthcare providers regarding a potential association between treatment of peripheral arterial disease with paclitaxel-coated balloons or paclitaxel-eluting stents and increased late mortality. ^[28]  This notification was updated in December 2021 on an FDA Web page that listed paclitaxel-coated balloons and stents approved in the United States, provided recommendations for healthcare providers, and described the risks associated with these devices. ^[29]

Exercise plays a vital role in the treatment of claudication. Patients with PAOD reduce their daily walking because of the claudication pain they experience and their fear of causing further damage. Unfortunately, this leads to an increasingly sedentary lifestyle that is even more detrimental to their health.

In most patients with claudication, regular walking programs result in substantial improvement (80-234% in controlled studies). A daily walking program of 45-60 minutes is recommended. The patient walks until claudication pain occurs, rests until the pain subsides, and then repeats the cycle.

Although the exact mechanism by which exercise improves walking distance remains unknown, a meta-analysis found that the mechanism is most likely to be multifactorial, including changes in cardiorespiratory physiology, endothelial function, mitochondrial number and activity, and muscle conditioning. ^[30] Regular exercise is believed to condition muscles so that they work more efficiently (ie, extract more blood) and to increase collateral vessel formation.

Patients who are treated medically should be seen every 4-6 months to assess the effects of therapy. Any changes in walking distance, smoking habits, eating habits, or exercise performance should be reviewed. Hypertension and diabetes should be controlled if necessary. Finally, a repeat pulse examination should be performed and the ABI measured. If the patient’s symptoms are worsening, intervention and referral to a vascular surgeon may be warranted.