Claudication as an ‘Orphan Disease’: Rationale and Goals of Drug Therapy for Peripheral Arterial Disease

Abstract

Patients with peripheral arterial disease are often perceived to suffer from a disorder whose pathogenesis and symptoms are not amenable to drug therapies. This clinical misperception remains prevalent despite an abundance of data suggesting that diverse pharmacotherapies may modulate the natural history of this disease. Patients with chronic limb arterial occlusive disease suffer from a disease that is characterized by: (1) a prolonged asymptomatic state that can be identified by simple physical examination and confirmed by measurement of the ankle brachial index; (2) a multi-year period of symptomatic claudication; and (3) a variable rate of progression to critical limb ischemia or acute arterial occlusion. This stage-dependent disease progression is mediated via the dynamic, but as yet incompletely understood, interaction of factors that elicit endothelial dysfunction, atherogenesis, and thrombosis. Current data suggest that each of these contributory disease processes can be modulated by extant pharmacotherapies. Additionally, many novel pharmacotherapeutic agents that are currently under investigation may further improve the ability of clinicians to modulate these fundamental biologic processes. Pharmacologic therapies should be targeted to decrease the rate of limb arterial disease progression, to improve limiting symptoms, and to prolong life. Symptoms of claudication can be objectively assessed via both exercise testing and disease-specific questionnaires. The presence of lower extremity atherosclerotic disease is predictive of the presence of coronary heart disease and a foreshortened five-year survival. Current data suggest that clinical investigations should be able to effectively stratify this relative risk via use of both clinical variables (e.g., age, diabetes mellitus, tobacco use, etc.) or by measurement of the ankle brachial index (ABI). The role of the physician is to decrease suffering and to prolong life. Judicious administration of medical therapies can play a critical role in helping the vascular practitioner accomplish these goals.