Return to Symposia Highlights for the Primary-Care Physician                                        Print This
 
A Primary Care Approach to the Management of PAD and Intermittent Claudication  

Introduction

Peripheral arterial disease (PAD) is a common atherosclerotic disorder that limits blood flow to the limbs. Intermittent claudication (IC) is the primary symptom of PAD, and is characterized by pain, aching, cramping, or fatigue in the working skeletal muscles caused by insufficient blood flow to meet the metabolic demands associated with sustaining the activities of daily living. PAD is associated with considerable morbidity and mortality and causes a diminution of quality of life. The diagnosis and management of PAD and IC present many challenges to office-based clinicians. Primary care practitioners are, however, well-positioned to play a pivotal role in reducing the morbidity and mortality associated with PAD and for improving the functional status of individuals with intermittent claudication.

The past decade has witnessed the dissemination of many new pharmacologic, exercise, percutaneous, and surgical approaches that can improve the well-being of those individuals who suffer PAD and intermittent claudication. Nearly every patient with PAD can achieve both functional improvement and can diminish their ischemic cardiovascular risk by application of one or a combination of therapeutic approaches. Most critically, individuals with PAD can now be offered a therapeutic choice.

The Prevalence of PAD and Claudication

PAD is a common atherosclerotic syndrome the prevalence of which depends upon the age of the population evaluated, their risk factor burden, and the diagnostic techniques used to detect PAD. Multiple epidemiologic studies thus provide evidence that suggest that PAD is almost as common as coronary artery disease, even though it is less frequently recognized nor treated in clinical practice (Ness J, Aronow WS. Prevalence of coexistence of coronary artery disease, ischemic stroke, and peripheral arterial disease in older persons, mean age 80 years, in an academic hospital-based geriatrics practice. J Am Geriatr Soc 1999;47:1255-1256).

Despite its high prevalence, only a fraction of those affected present with easily recognized leg ischemic symptoms. For every patient who describes classic claudication, another three have either atypical symptoms or no leg symptoms, despite a considerable atherosclerotic risk burden. Current office practice does not actively identify individuals with either claudication, nor those with asymptomatic PAD, leading to an underestimate of its prevalence in our communities. The presence of PAD in a patient, as a manifestation of systemic atherosclerosis, should lead the clinician to suspect the presence of other atherosclerotic syndromes (Aronow WS, Ahn C. Prevalence of coexistence of coronary artery disease, peripheral arterial disease, and atherothrombotic brain infarction in men and women > or = 62 years of age. Am J Cardiol 1994;74:64-65). While these related atherosclerotic syndromes (coronary artery and cerebrovascular disease) may be asymptomatic and below the threshold of clinical detection, there are important clinical implications of this knowledge.

Initiation of atherosclerosis risk reduction interventions in PAD diminishes rates of myocardial infarction and stroke, offering an ideal opportunity to emplace effective cardiovascular preventive therapies.

Morbidity and Mortality

PAD is a powerful marker of short-term cardiovascular morbidity and mortality. The PAD diagnosis is associated with an approximate 3-fold increase mortality and 6-fold increased risk of cardiovascular events. Beyond its impact on mortality, PAD is also associated with a 5-6% annual rate of nonfatal myocardial infarction or stroke. Although many clinicians and patients do not perceive PAD to be dangerous, its risk is greater than that of many common cancers. The five-year mortality for patients with PAD is 32%, and exceeds that of breast cancer, Hodgkin’s Disease, and prostate cancer (American Cancer Society. Cancer Facts and Figures, 2000; Criqui MH, et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992;326:381-386). While past clinical PAD care provided a primary focus on the role of revascularization, over the five years after diagnosis, this cardiovascular risk and major diminution of functional capacity should remain the focus of care in office practice. Over this approximate time frame, only appropriately 7% of individuals with PAD will require surgical bypass or endovascular intervention, and only 4% will eventually require amputation. Prompt identification of severe PAD and critical limb ischemia offers the potential to avert limb loss (Weitz JI, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation 1996;94:3026-3049).

PAD, Functional Status, and Quality of Life

PAD has a profound impact on limb function and quality of life. Maximum walking speed in individuals with claudication is often less than half that of those in good health. As well, the maximal distance that can be traveled is often severely reduced. Individuals with severe claudication have a loss of function that is similar to the impact of New York Heart Association Class III-IV heart failure. This diminishes the ability to participate independently in activities of daily living and has impact on work, avocational activities, and family life (Dawson DL, et al. Peripheral arterial disease: medical care and prevention of complications. Prev Cardiol 2002;5:119-130). The pathophysiology of claudication is significantly more complex than can be explained by the arterial stenosis alone. Limb ischemia may result in qualitative and quantitative changes in skeletal muscle fiber structure and function, with evidence of denervation, and impaired oxidative metabolism (Farinon AM, et al. Skeletal muscle and peripheral nerve changes caused by chronic arterial insufficiency--significance and clinical correlations--histological, histochemical and ultrastructural study. Clin Neuropathol 1984;3:240-25). Increased appreciation of this complex pathophysiology permits multiple therapeutic approaches, inclusive of exercise, medications, and revascularization to be associated with benefit.

The Role of Atherosclerosis Risk Factors

The risk factors for the development of PAD are similar to those for other common atherosclerotic syndromes, and include smoking, diabetes, dyslipidemia, hypertension, age, hyperhomocysteinemia, and obesity. Of these, the modifiable risk factors, smoking and diabetes, contribute most heavily to disease progression in the patient with PAD.

Smoking is a potent modulator of the natural history of PAD. Tobacco use rapidly accelerates progression of limb atherosclerosis, and is associated with more rapid progression of mild claudication to severe claudication or critical limb ischemia, reduces the longevity of all revascularization procedures, increases amputation rates, increases rates of myocardial infarction and stroke, and profoundly decreases patient survival. Smoking synergistically enhances the atherogenic effects of other risk factors, including diabetes and hypercholesterolemia. All individuals with PAD who smoke require immediate smoking cessation interventions, and should be offered the frank information that smoking cessation may literally make the difference between life and death. Patients with claudication who continue to smoke face as high as a 40% to 50% mortality rate at 5 years. Thus, a prolonged or passive “contemplative stage” prior to initiation of effective smoking interventions may compromise survival (Kannel WB, Shurtleff D. The Framingham Study. Cigarettes and the development of intermittent claudication. Geriatrics 1973;28:61-68).

Diabetes is also a powerful risk factor for the development of PAD, and accelerates the development of limb atherosclerosis by 200 to 400%. Diabetes also increases the risk of cardiac ischemic events two- to four-fold, increases the risk of stroke four-fold, and accelerates the development of clinically evident PAD by a decade. Individuals with impaired glucose tolerance demark a cohort with an increased risk of developing claudication by two-fold in men and four-fold in women. Individuals with PAD suffer more diffuse and distal arterial occlusive disease and are more likely to require leg revascularization procedures. Individuals with diabetes face a seven-fold higher risk of amputation as compared to PAD patients without diabetes (Cardiovascular Disease and Diabetes Mellitus. Symposium at 58th Annual Scientific Session, American Diabetes Association. Chicago, Ill. June 1998).

Establishing the PAD Diagnosis

The stepwise evaluation of individuals at risk for PAD should include collection of a history of walking impairment and risk factors, documenting the presence or absence of other ischemic symptoms; should include a focused vascular physical examination; and appropriate use of the ankle-brachial index (ABI) and other tools of the noninvasive vascular laboratory. For most individuals, these data can rapidly and cost-effectively establish the diagnosis, provide objective anatomic and functional data that may guide therapeutic choices, and will create a platform for subsequent patient education.

For some individuals with difficulty walking, establishment of a broad differential diagnosis can be challenging. Claudication symptoms do not always correlate with abnormalities on physical examination or with the ABI value alone. For example, some patients with very severe PAD may not experience claudication because another limb or systemic disease may limit mobility, such as arthritis, neuropathy, deconditioning, or emphysema. Moreover, many individuals with claudication are elderly and may consider their symptoms to be a natural consequence of aging. Such individuals may slowly diminish their walking so that classic claudication is neither experienced, nor reported to their primary care clinician. Conversely, clinicians have traditionally been insensitive to obtaining histories of functional impairment, so that patients with mild PAD and mild claudication with more vigorous activity are not identified when therapies may be particularly effective.

Symptomatic PAD is routinely underdiagnosed, despite the facility with which this diagnosis can be made in office practice. Establishment of the diagnosis permits the clinician to offer the patient achievement of two major therapeutic goals: diminution of cardiovascular ischemic risk and improvement in quality of life. PAD and claudication should be suspected in any patient complaining of ambulatory leg pain. Further, any patient over the age of 50 with multiple risk factors for PAD (such as smoking and diabetes) or any patient over the age of 70 should be considered at risk for PAD. Any patient who presents with a nonhealing wound should also be assessed for the presence of PAD.

The clinical history of claudication may provide clues to the sites of stenosis of the arteries of the lower limbs (the iliac, femoral, and popliteal arteries). Symptoms typically appear one level or more below the arterial stenosis. Claudication symptoms in the buttocks or thighs, or erectile dysfunction, may imply distal aortic or iliac arterial disease. Claudication in the thigh or calf may indicate a stenosis inthe common or superficial femoral arteries or its branches. Distal femoral or popliteal arterial disease may elicit claudication in the calf, ankle or, quite rarely, the foot.

Classic claudication is often described by the patient as “aching,” “cramping,” “tightness,” or “tiredness” that occurs in leg muscle groups, but not in joints. Claudication is usually reproduced by exercise, and is relieved within 2 to 5 minutes of stopping. The use of a history of claudication and an abnormal ABI is over 95% accurate if these are performed correctly. A careful patient history can efficiently focus on some specific clinical questions (see box) (Regensteiner JG, et al. Evaluation of walking impairment by questionnaire in patients with peripheral artery disease. J Vasc Med and Biol 1990;2:142-152).

Clinicians in office practice should consider performance of a vascular physical examination for PAD on all patients who are at risk. This examination should include the abdomen, which should be auscultated for bruits, and should be palpated for an aortic aneurysm. Palpate the femoral, popliteal, posterior tibial, and dorsalis pedis pulses. Note the presence or absence of a pulse and record its grade in the chart. Evaluate the patient’s feet – including between the toes – for signs of poor circulation, infection, ulcers, fissures, calluses, or tinea. Assess overall foot skin care. This is particularly important in diabetic patients.

The ABI is one of the most useful diagnostic tools available for the accurate assessment of PAD and its severity. It is a simple, inexpensive, noninvasive, and objective technique that is readily performed either in the office setting or that is available in any vascular laboratory. The ABI is calculated from the Doppler-derived ratio of systolic blood pressure in the ankle to systolic blood pressure in the arm. The normal ABI value is greater than 1.0. Any ABI below 0.9 accurately establishes the PAD diagnosis (Dawson DL, et al. Peripheral arterial disease: medical care and prevention of complications. Prev Cardiol 2002;5:119-130).

While most individuals can be provided with comprehensive lifelong care in office practice, it is important to recognize when individuals with PAD should be referred to a vascular specialist. Most office practices will be ideal sites for establishment of the PAD diagnosis, and for consideration of a broader differential diagnosis when symptoms are atypical. Once the diagnosis is clear, an annual health assessment, treatment of claudication (via prescription of supervised exercise or pharmacotherapy), instruction in foot care, use of antiplatelet therapies, and risk factor normalizations should be performed. PAD patients with severe claudication that is refractory to exercise or pharmacologic intervention should usually not be managed in the primary care setting, and specialty referral is indicated. Symptoms of ischemic rest pain (which is indicative of severe arterial disease), ulcers, or gangrene also require the immediate care of a vascular specialist.

Supervised Exercise Training as a Primary Claudication Treatment

The efficacy of claudication exercise training has been established by numerous investigations over the past decade. Exercise training is proven to increase both the pain-free walking distance and the maximal walking distance. For the compliant patient in a supervised therapeutic program, it is reasonable for patients to expect to double their pain-free or total walking distances. While many clinicians continue to speculate that exercise may be effective by improving collateral blood flow, current data do not support this hypothesis. In contrast, exercise is known to improve skeletal muscle metabolism, gait, endothelial function, and to diminish systemic inflammatory markers (Gardner AW, Poehlman ET. Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis. JAMA 1995;274:975-980). Many clinicians and patients may derive a sense of wonder that major functional improvements can be obtained from supervised exercise programs in the absence of a readily explicable and documented physiologic mechanism, although many effective therapies defy easy mechanistic explanation. As well, clinicians should know that casual office advice to “go home and exercise” is known to be ineffective. Exercise for PAD and claudication is a defined medical procedure that is best performed in a supervised setting, by experienced exercise physiologists, nurses, or physical therapists, and this efficacy is now sanctioned by CPT code 93668 (Regensteiner JG, et al. Hospital vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease. Angiology 1997;48:291-300). While the efficacy of PAD rehabilitative techniques is proven, and cardiac rehabilitation programs are well-positioned to provide this intervention, continued lack of reimbursement by health care payors serves as a major impediment that limits program availability in the United States, denying individuals with claudication a safe and cost-effective therapeutic opportunity.

PAD Pharmacotherapy

While PAD and intermittent claudication are best managed through early identification, modification of risk factors, and exercise, pharmacotherapy is usually still required in order to minimize systemic ischemic risk (e.g., antiplatelet medications) and to offer maximal opportunities for diminution of claudication symptoms. Several pharmacotherapeutic options can effectively modify the natural history of PAD and improve outcomes for patients. The ideal medical therapy for PAD would improve claudication symptoms, forestall the onset of limb-threatening events, decrease the revascularization rate, and improve patients’ long-term survival. While no single medication can effect all of these changes, these comprehensive goals can be achieved by use of lifestyle, exercise, and pharmacological interventions.

At present, only two medications carry an indication to improve the symptoms of claudication. Cilostazol was approved in 1999, and pentoxifylline was approved in 1984. These two drugs have distinctly different mechanisms of action. Cilostazol is a PDE-III inhibitor, which increases cAMP levels in vascular smooth muscle and platelets with subsequent inhibition of platelet aggregation accompanied by vasodilation. Cilostazol also makes a modest improvement in two of the dyslipidemias implicated in PAD and atherosclerosis: it raises HDL-C and lowers triglyceride levels. Pentoxifylline is a hemorheologic agent, a synthetic dimethylxanthine derivative that is structurally related to theophylline and caffeine. There is no clear consensus in the scientific community regarding the clinical efficacy of pentoxifylline.

Antiplatelet therapy is also important in managing all patients with PAD. No antiplatelet medication (e.g., aspirin or clopidogrel) is indicated to improve claudication symptoms. However, these medications should be prescribed to decrease the risk of acute ischemic events, such as stroke or MI. Aspirin blocks prostaglandin synthase, which is necessary for the formation of the platelet-aggregating factor thromboxane A2. Clopidogrel is an antiplatelet agent that selectively inhibits the ability of ADP to bind to its platelet receptor, thereby halting activation of the ADP-mediated glycoprotein IIb-IIIa complex. Much like aspirin, clopidogrel irreversibly inhibits platelet aggregation over the life span of any platelet exposed to it. Clopidogrel is indicated to decrease rates of heart attack and stroke in individuals with established cardiovascular disease, such as prior myocardial infarction, prior stroke or PAD.

In order to further minimize ischemic risk additional medical interventions can be effective, such as the use of lipid-lowering therapies, optimally through the use of HMG-CoA reductase inhibitors, or statins. Since PAD is an atherosclerotic process, it is important to decrease serum lipid levels to target levels established by the National Cholesterol Education Program Adult Treatment Panel III (MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Heart Protection Study Collaborative Group; Lancet 2002;360:7-22).

Additional adjunctive medications may be useful, including antihypertensive medications such as ACE inhibitors, diuretics, beta blockers, and calcium channel blocking medications.

Revascularization

Selected individuals may present with severe claudication that is refractory to pharmacotherapy and exercise, or present with severe limb ischemia. These patients require prompt vascular specialty referral and consideration for revascularization in order to assure the best opportunity to improve limb symptoms and to assure effective limb salvage. Although there is no absolute consensus on the severity of limb symptoms or hemodynamic parameters that best identify patients for surgical or endovascular revascularization, clinicians in practice should gain experience with scenarios in which clinical presentations suggest the efficacy of revascularization and which therapies are particularly effective, safe, and durable (e.g., angioplasty and stenting of proximal aortoiliac arterial disease). There are a variety of effective revascularization techniques, including surgical bypass grafting and percutaneous transluminal angioplasty (PTA). Careful patient selection can assure that invasive procedures are offered to those in which the therapeutic benefit clearly outweighs the procedural risk (Weitz JI, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation 1996;94:3026-3049).

Summary

PAD is common, associated with a high cardiovascular ischemic risk and diminution of quality of life. The diagnosis of PAD is easily established, permitting the prescription of therapies that can avert myocardial infarction, stroke, and death, and that can preserve functional independence. These are goals shared by all individuals with PAD, and office practice provides an ideal setting for the initiation and continuation of lifelong effective vascular care.

Return to Symposia Highlights for the Primary-Care Physician                                      Print This

All contents Copyright © 1999 - 2003 Medical Association Communications