Peripheral Arterial Disease: Medical Care/ Complications

Abstract and Introduction

Peripheral arterial disease (PAD) is a common but under-recognized problem affecting older patients. Intermittent claudication is the most frequent symptom of PAD, although the diagnosis of PAD is often overlooked until the patient presents with limb-threatening ischemia. Importantly, PAD is a marker for generalized atherosclerosis and is closely associated with coronary and cerebrovascular disease. The severity of PAD has been correlated with an increased risk of myocardial infarction, stroke, and cardiovascular death. The recognition and diagnosis of PAD, combined with its appropriate medical management, may well reduce the overall risk of cardiovascular morbidity. When diagnosed early, both exercise and pharmacotherapy can ameliorate symptoms of claudication, augment functional performance, and improve quality of life.

Peripheral arterial disease (PAD) is commonly encountered in general practice. PAD should be recognized as an important marker for cardiovascular disease, but specific therapy directed to the management of PAD manifestations is indicated for most patients.

There is a need for a standardized, evidence-based management approach to PAD. This need provided the impetus for the development and recent publication of consensus recommendations for most aspects of PAD care.^[1] These recommendations were developed through a 3-year process of collaboration between North American and European vascular professional societies, in the fields of cardiology, vascular medicine, radiology, and surgery. The product of this long, collaborative process, the TransAtlantic Inter-Society Consensus, also identified many unresolved critical issues, including the uncertain benefits and cost effectiveness of many widely used diagnostic and therapeutic modalities.

This paper provides a review for physicians who care for patients with known or occult PAD, focusing on the epidemiology, office-based diagnostic evaluation, general medical management, and specific therapeutic options for patients with intermittent claudication. Because PAD is a manifestation of generalized atherosclerosis, the principal issue in medical management of PAD is the development of a treatment plan that modifies known risk factors for atherosclerosis and its atherothrombotic complications. It is also recognized that selected patients with disabling claudication symptoms may benefit from surgical therapy or catheter-based interventions, but most PAD patients do not require revascularization procedures. In contrast, this review focuses on global PAD management approaches that are needed for quality long-term PAD care, as offered by the primary care clinician/family physician, general internist, adult nurse practitioner, physician's assistant, or cardiologist.

The views expressed herein are those of the authors and do not reflect the official policy of the Department of Defense or other departments of the US government.

Cite this: Peripheral Arterial Disease: Medical Care and Prevention of Complications - Medscape - Jun 01, 2002.

Table I. Medical Management Guidelines for Peripheral Arterial Disease (PAD)
Goals	Therapy	Comments
Antiplatelet therapy	Aspirin (ASA) Clopidogrel (Plavix)	Risk of MI, stroke, vascular death^[23,25] ASA may reduce need for surgery for PAD^[24] Clopidogrel may be more effective than ASA for risk reduction for PAD patients^[26]
Management of Specific Atherosclerotic Risk Factors
Cigarette smoking	Behavioral programs Nicotine replacement	Risk of PAD progression, MI, stroke, death^[49,50]
Obesity	Bupropion (Zyban, Wellbutrin) Dietary modification Physical activity	Risk of critical ischemia and limb loss^[20]
Diabetes mellitus	Dietary therapy Oral hypoglycemics; metformin (Glucophage); and others Insulin	Intensive glycemic control may improve outcomes, including risk of MI and death^[51,52,53] Recommend fasting blood glucose 80-120 mg/dL; postprandial glucose <180 mg/dL; HbA_1c<7.0%
Hyperlipidemia	Screen all PAD patients Dietary modification Statin medication if LDL-C ≥130 mg/dL; target LDL-C <100 Consider niacin for low HDL-C Consider fibrates for low HDL-C and high triglycerides	Lp(a) is an independent risk factor for PAD^[54] PAD may stabilize or regress with therapy^{[55,56,57,58,59]} Risk of PAD progression^[60] Risk of MI and CV death^[61,62,63]
Hypertension	Manage according to guidelines of Joint National Committee of National Heart, Lung, and Blood Institute	Correlation with PAD progression not established Marked in systolic pressure may slightly worsen claudication symptoms^[64] No contraindication to blocker use^[65] ACE inhibitor (ramipril [Altace]) may risk of MI or death in PAD patients^[66]
Hypercoagulable states	Warfarin (Coumadin)	No data to support CV risk reduction or PAD symptom improvement; use warfarin in context of other proven indications
Hyperhomocysteinemia	Folic acid Vitamin B₁₂ Vitamin B₆	Elevated plasma homocysteine is an important PAD risk factor in patients <50 years^[67] Treatment may risk of CV events and death,^[68,69] but current role unproven
Postmenopausal state	Hormone replacement therapy (estrogen and progesterone)	Risk of CV events in women in epidemiologic studies,^[70] but benefit not shown in prospective trials

MI=myocardial infarction; HbA1C=hemoglobin A1C; LDL-C=low-density lipoprotein cholesterol; HDL-C=high-density lipoprotein cholesterol; Lp(a)=lipoprotein(a); ACE=angiotensin-converting enzyme; CV=cardiovascula

Table II. Pharmacotherapy for Symptoms of Intermittent Claudication
FDA-Approved Drugs (Recommended Options)
Cilostazol
Pentoxifylline
Other Established Drugs With Some or Potential Benefit for Claudication
Buflomedil
Naftidrofuryl
Therapies With Minimal or No Benefit (Not Recommended for Clinical Use)
Aminophylline	Isovolumic hemodilution
Anticoagulants	Ketanserin
Antiplatelet drugs	Nicotinic acid derivatives
Cinnarizine	Vasodilators
Defibrotide	Verapamil (and other calcium channel blockers)
Dextran	Vitamin E
Ginkgo biloba
Isosuprine
Incompletely Studied Drugs With Potential Benefit (Not Yet FDA-Approved)
Carnitine
L-arginine
Propionyl-L-carnitine
Prostaglandins and prostanoids (beraprost sodium and others)
Protein kinase C inhibitors
Vascular endothelial growth factor

FDA=Food and Drug Administration

Table III. Comparision of Current Drug Therapies for Intermittent Claudication
Agent	Clinical Indication	Dose	Potential Adverse Events	Contraindication
Cilostazol (Otsuka America Pharmaceutical, Inc.)	Reduction of symptoms of intermittent claudication	50 or 100 mg, twice daily	Headache, nausea, diarrhea or loose stools, palpitations	Congestive heart failure of any severity (i.e., left ventricular systolic dysfunction)
Pentoxifylline (Hoechst Marion Roussel)	Treatment of intermittent claudication on the basis of chronic occlusive arterial disease of the limbs	400 mg, three times daily	Gastrointestinal disturbances, headache, dizziness	Recent cerebral and/or retinal hemorrhage, previous intolerance to methylxanthines

Compiled and adapted from manufacturers' FDA-approved labeling information.

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Peripheral Arterial Disease: Medical Care and Prevention of Complications

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