Treatment and Prevention of Peripheral Arterial Disease

Peripheral arterial disease (PAD) affects approximately 8 to 12 million people in the United States.[1] The prevalence of PAD among patients with diabetes is estimated to be 10% in people above age 40 and as high as 20% among those with diabetes who are over the age of 50.[2] Diabetes and smoking are the strongest risk factors for PAD. Other well-known risk factors include advanced age, hypertension, and hyperlipidemia.[1,3] A recent study found that many physicians routinely do not obtain a relevant history for PAD, and the symptoms of PAD are often subtle and frequently overlooked, especially among patients with diabetes who also frequently have concomitant neuropathy.[4] The most frequent symptom of PAD is intermittent claudication, or muscle pain that occurs with activity and is relieved during rest.[1] Guidelines for the management of PAD appear in Figure 1.

Figure 1. Management of peripheral arterial disease[5]

Nonsurgical treatment

Nonsurgical therapy for PAD involves lifestyle modification and pharmacologic therapy. Lifestyle modification is extremely effective in the treatment of PAD.

Lifestyle modification

Cessation of smoking

Cigarette smoking is the single most important modifiable risk factor for improving PAD. In patients with PAD, tobacco use is associated with increased progression of atherosclerosis as well as increased risk of amputation. Smoking-cessation counseling and avoidance of all tobacco products are absolutely essential.[5,6]

Physical activity

Since 1966, many randomized controlled trials have demonstrated the benefit of supervised physical activity training in individuals with PAD. The most beneficial outcomes have been seen after 3 months of treadmill walking 3 times per week. Physical activity is associated with minimal morbidity and improved functional capacity.[7,8]

Pharmacologic therapies

Antiplatelet therapy

The use of aspirin to prevent cardiovascular events and death in patients with PAD is considered equivocal; however, aspirin therapy for people with diabetes is recommended by the American Diabetes Association.[9] The Antiplatelet Trialists’ Collaboration reviewed 145 randomized patients and questioned whether patients with diabetes may derive more benefit from clopidogrel than aspirin.[10]

Dyslipidemia treatment

Although treating dyslipidemia decreases cardiovascular morbidity and mortality in general, even greater improvements have been seen among patients with diabetes.[9] In The Heart Protection Study, subjects over age 40 with diabetes and a total cholesterol >135 mg/dL reduced by approximately 25% their risk of first major coronary events by achieving a reduction in LDL cholesterol of approximately 30% from baseline with statin therapy. This reduced risk was independent of baseline LDL, preexisting vascular disease, type of diabetes, length of diabetes or glycemic control.[9]  In the subgroup analysis of the Scandinavian Simvastatin Survival Study, the reduction in LDL cholesterol level by simvastatin was associated with a 42% reduction in coronary death and 34% reduction in the risk of major coronary events.[11]

Other Therapies

Pentoxifylline was approved by the FDA in 1984 for treating claudication, though there is no clear evidence that it significantly improves walking distance.[12,13] Cilostazol, an oral phosphodiesterase type III inhibitor, was the second drug to gain FDA approval for treating intermittent claudication. Significant benefit has been demonstrated in increasing maximal walking time and improving functional status and health-related quality of life in several randomized trials.[12-14] A summary of pharmacologic therapies appears in Table 1.

Table 1. Pharmacotherapy for patients with claudication[5]

Indications for revascularization

The indications for limb revascularization are disabling claudication, pain at rest or tissue loss which has been refractory to other therapy. Although most ischemic limbs can be revascularized, some cannot. The need for amputation occurs when there is difficulty in obtaining appropriate target vessels beyond the obstruction, or irreversible gangrene beyond the obstruction precludes revascularization.[13]

Prevention

Preventive strategies which can improve peripheral arterial disease among patients with diabetes include intensive management of glucose, lipids, hypertension, and smoking cessation. Though most of the data on glycemic control point towards its most direct impact being on microvascular complications, the relationship between improved glycemic control with prevention and or delay in neuropathy has been well established. Glycemic control is the cornerstone for improved outcomes. Among patients with diabetes who are hospitalized, improved outcomes are seen in diverse areas of wound care management when glucose control as close as possible to normal is achieved.

Conclusion

Patients with diabetes have numerous risk factors for the development of PAD. A systematic approach to medical care which includes optimizing glucose, blood pressure and cholesterol, as well as using antiplatelet therapy, with concomitant daily exercise, may help delay or prevent the onset and/or progression of PAD. Aggressive risk factor modification among all patients with diabetes may reduce the morbidity and mortality associated not only with PAD, but with other microvascular and macrovascular morbidities associated with diabetes.

References

1. American Heart Association. PAD quick facts. Available at http://www.americanheart.org/presenter.jhtml?identifier=3020248. Accessed May 1, 2004.
2. Gregg EW, Sorlie P, Paulose-Ram R, et al. Prevalence of lower-extremity disease in the US adult population ≥40 years of age with and without diabetes: 1999-2000 National Health and Nutrition Examination Survey. Diabetes Care. 2004;27:1591-1597.
3. Criqui MH. Peripheral arterial disease - epidemiological aspects. Vasc Med. 2001;6(suppl 1):3-7.
4. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001;286:1317-1324
5. Gey DC, Lesho EP, Mangold J. Management of peripheral arterial disease. Am Fam Physician. 2004;69:525-532.
6. Lassila R, Lepantalo M. Cigarette smoking and the outcome after lower limb arterial surgery. Acta Chir Scand. 1988;154:635-640.
7. Larsen OA, Lassen NA. Effect of daily muscular exercise in patients with intermittent claudication. Lancet. 1966;2:1093–1096.
8. Leng GC, Fowler B, Ernst E. Exercise for intermittent claudication. Cochrane Database Syst Rev. 2000 [Art No: CD000990].
9. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28(Suppl 1):S4-S36.
10. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Br Med J. 1994;308:81–106.
11. Kjekshus J, Pedersen TR, for the Scandinavian Simvastatin Survival Study Group. Reducing the risk of coronary events: evidence from the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol. 1995;76:64C–68C.
12. Jaff MR. Pharmacotherapy for peripheral arterial disease: emerging therapeutic options. Angiology. 2002;53:627-633.
13. Fernandez BB. A rational approach to diagnosis and treatment of intermittent claudication. Am J Med Sci. 2002;323:244-251.
14. Regensteiner JG, Ware JE Jr, McCarthy WJ, et al. Effect of cilostazol on treadmill walking, community-based walking ability, and health-related quality of life in patients with intermittent claudication due to peripheral arterial disease: meta-analysis of six randomized controlled trials. J Am Geriatr Soc. 2002;50:1939–1946.