Clinical Evidence: A Publication of BMJ Publishing Group

Peripheral Arterial Disease

Am Fam Physician. 2002 Jun 1;65(11):2321-2322.

Questions Addressed

  • What are the effects of treatments for chronic peripheral arterial disease?

Summary of Interventions

Beneficial

Antiplatelet treatment

Exercise

Likely to be beneficial

Smoking cessation

Cilostazol

Percutaneous transluminal angioplasty (transient benefit only)

Unknown effectiveness

Pentoxifylline

Bypass surgery

To be covered in future issues of Clinical Evidence

Lipid-lowering therapy

Levocarnitine

Naftidrofuryl

Beraprost

Ginkgo biloba

Anticoagulation

Vitamin E

Indobufen

Defibrotide

Buflomedil

Thrombolysis for acute limb ischemia

Beta blockers and peripheral vascular disease

Improved glycemic control in people with diabetes

Summary of Interventions

View Table

Summary of Interventions

Beneficial

Antiplatelet treatment

Exercise

Likely to be beneficial

Smoking cessation

Cilostazol

Percutaneous transluminal angioplasty (transient benefit only)

Unknown effectiveness

Pentoxifylline

Bypass surgery

To be covered in future issues of Clinical Evidence

Lipid-lowering therapy

Levocarnitine

Naftidrofuryl

Beraprost

Ginkgo biloba

Anticoagulation

Vitamin E

Indobufen

Defibrotide

Buflomedil

Thrombolysis for acute limb ischemia

Beta blockers and peripheral vascular disease

Improved glycemic control in people with diabetes

Definition

Peripheral arterial disease arises when there is significant narrowing of arteries distal to the arch of the aorta. Narrowing can arise from atheroma, arteritis, local thrombus formation, or embolization from the heart or more central arteries. This topic includes treatment options for people with symptoms of reduced blood flow to the leg that are likely to arise from atheroma. These symptoms range from calf pain on exercise (intermittent claudication), to rest pain, skin ulceration, or ischemic necrosis (gangrene) in people with critical ischemia.

Incidence/Prevalence

Peripheral arterial disease is more common in people older than 50 years than in younger people, and is more common in men than in women. The prevalence of peripheral arterial disease of the legs (assessed by noninvasive tests) is about 3 percent in people younger than 60 years, but rises to greater than 20 percent in people older than 75 years.1 The overall annual incidence of intermittent claudication is 1.5 to 2.6 per 1,000 men a year and 1.2 to 3.6 per 1,000 women a year.2

Etiology/Risk Factors

Factors associated with the development of peripheral arterial disease include age, gender, cigarette smoking, diabetes mellitus, hypertension, hyperlipidemia, obesity, and physical inactivity. The strongest association is with smoking (relative risk [RR]: 2.0 to 4.0) and diabetes (RR: 2.0 to 3.0).3 Acute limb ischemia may result from thrombosis arising within a peripheral artery or embolic occlusion.

Prognosis

The symptom of intermittent claudication can resolve spontaneously, remain stable over many years, or progress rapidly to critical limb ischemia. The incidence of critical limb ischemia in Denmark and Italy in 1990 was 0.25 to 0.45 per 1,000 people a year.4,5 About 15 percent of people with intermittent claudication eventually develop critical leg ischemia, which endangers the viability of the limb. Coronary heart disease is the major cause of death in people with peripheral arterial disease of the legs. Over five years, about 20 percent of people with intermittent claudication have a nonfatal cardiovascular event, myocardial infarction (MI), or stroke.6 The mortality rate of people with peripheral arterial disease is two to three times higher than that of age- and sex-matched controls. Overall mortality after the diagnosis of peripheral arterial disease is about 30 percent after five years and 70 percent after 15 years.6

Clinical Aims

To reduce symptoms (intermittent claudication), local complications (arterial leg ulcers, critical leg ischemia), and general complications (MI and stroke).

Clinical Outcomes

Local outcomes: Proportion of people with adverse outcomes (decline in claudication distance, amputation, adverse effects of treatment), the mean improvement in claudication distance measured on a treadmill or by some other specified means. We did not include studies that reported other measures such as patency assessed by angiography or ultrasound. General outcomes: Rates of MI, stroke, and other major cardiovascular events.

Definition

Peripheral arterial disease arises when there is significant narrowing of arteries distal to the arch of the aorta. Narrowing can arise from atheroma, arteritis, local thrombus formation, or embolization from the heart or more central arteries. This topic includes treatment options for people with symptoms of reduced blood flow to the leg that are likely to arise from atheroma. These symptoms range from calf pain on exercise (intermittent claudication), to rest pain, skin ulceration, or ischemic necrosis (gangrene) in people with critical ischemia.

Incidence/Prevalence

Peripheral arterial disease is more common in people older than 50 years than in younger people, and is more common in men than in women. The prevalence of peripheral arterial disease of the legs (assessed by noninvasive tests) is about 3 percent in people younger than 60 years, but rises to greater than 20 percent in people older than 75 years.1 The overall annual incidence of intermittent claudication is 1.5 to 2.6 per 1,000 men a year and 1.2 to 3.6 per 1,000 women a year.2

Etiology/Risk Factors

Factors associated with the development of peripheral arterial disease include age, gender, cigarette smoking, diabetes mellitus, hypertension, hyperlipidemia, obesity, and physical inactivity. The strongest association is with smoking (relative risk [RR]: 2.0 to 4.0) and diabetes (RR: 2.0 to 3.0).3 Acute limb ischemia may result from thrombosis arising within a peripheral artery or embolic occlusion.

Prognosis

The symptom of intermittent claudication can resolve spontaneously, remain stable over many years, or progress rapidly to critical limb ischemia. The incidence of critical limb ischemia in Denmark and Italy in 1990 was 0.25 to 0.45 per 1,000 people a year.4,5 About 15 percent of people with intermittent claudication eventually develop critical leg ischemia, which endangers the viability of the limb. Coronary heart disease is the major cause of death in people with peripheral arterial disease of the legs. Over five years, about 20 percent of people with intermittent claudication have a nonfatal cardiovascular event, myocardial infarction (MI), or stroke.6 The mortality rate of people with peripheral arterial disease is two to three times higher than that of age- and sex-matched controls. Overall mortality after the diagnosis of peripheral arterial disease is about 30 percent after five years and 70 percent after 15 years.6

Clinical Aims

To reduce symptoms (intermittent claudication), local complications (arterial leg ulcers, critical leg ischemia), and general complications (MI and stroke).

Clinical Outcomes

Local outcomes: Proportion of people with adverse outcomes (decline in claudication distance, amputation, adverse effects of treatment), the mean improvement in claudication distance measured on a treadmill or by some other specified means. We did not include studies that reported other measures such as patency assessed by angiography or ultrasound. General outcomes: Rates of MI, stroke, and other major cardiovascular events.

Evidence-Based Medicine Findings

search date: CLINICAL EVIDENCE SEARCH AND APPRAISAL MAY 2001

Evidence-Based Medicine Findings

search date: CLINICAL EVIDENCE SEARCH AND APPRAISAL MAY 2001

Antiplatelet Agents

One systematic review has found strong evidence that antiplatelet agents versus control treatments reduce the rate of major cardiovascular events and local arterial occlusion in people with peripheral arterial disease. The balance of benefits and harms is in favor of treatment for most people with peripheral arterial disease because they are at greater risk of cardiovascular events.

Exercise

Systematic reviews have found that regular exercise three times a week for 30-minute sessions significantly improves the limitation of walking by claudication.

Smoking Cessation

An old systematic review found observational evidence that continued cigarette smoking by people with intermittent claudication is associated with an increased rate of cardiovascular outcomes such as MI, stroke, and death. Another systematic review has found no good evidence from controlled studies about advice to stop smoking in people with intermittent claudication.

Cilostazol

Four randomized controlled trials (RCTs) of cilostazol versus placebo in people with intermittent claudication have found improved initial claudication distance and absolute claudication distance measured on a treadmill, and a reduced proportion of people whose symptoms did not improve. The moderate withdrawal rate in the cilostazol arm of the RCTs reduces confidence in these conclusions.

Pentoxifylline

Systematic reviews of many small RCTs of variable quality have found that pentoxifylline versus placebo increases the walking distance in people with intermittent claudication. One recently published RCT with a high withdrawal rate found no convincing benefit with pentoxifylline versus placebo in people with intermittent claudication. The available evidence is not good enough to define clearly the effects of pentoxifylline.

Percutaneous Transluminal Angioplasty

One systematic review of two small RCTs found limited evidence that angioplasty versus no angioplasty improved total walking distance in the short term, but had no long-term benefits.

Bypass Surgery

We found only limited evidence from small RCTs using proxy outcomes for the consensus view that bypass surgery is the most effective treatment for people with debilitating symptomatic peripheral arterial disease.

Adapted with permission from Anand SS, Creager MA. Peripheral arterial disease. Clin Evid 2001;6:70–81.

 

REFERENCES

1. Fowkes FG, Housley E, Cawood EH, et al. Edinburgh Artery Study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. Int J Epidemiol. 1991;20:384–92.

2. Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication. J Am Geriatr Soc. 1985;33:13–8.

3. Murabito JM, D'Agostino RB, Silbershatz H, et al. Intermittent claudication: a risk profile from the Framingham Heart Study. Circulation. 1997;96:44–9.

4. Catalano M. Epidemiology of critical limb ischemia: north Italian data. Eur J Med. 1993;2:11–4.

5. Ebskov L, Schroeder T, Holstein P. Epidemiology of leg amputation: the influence of vascular surgery. Br J Surg. 1994:81:1600–3.

6. Leng GC, Lee AJ, Fowkes FG, et al. Incidence, natural history and cardiovascular events in symptomatic and asymptomatic peripheral arterial disease in the general population. Int J Epidemiol. 1996;25:1172–81.

This is one in a series of chapters excerpted from Clinical Evidence, published by the BMJ Publishing Group, Tavistock Square, London, United Kingdom. Clinical Evidence is published in print twice a year and is updated monthly online. The complete text for this topic, as well as additional information, is available to subscribers at www.clinicalevidence.com. This series is part of AFP's CME. See “Clinical Quiz” on page 2205.


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