Atherosclerosis 187 (2006) 221–237 Review Intermittent claudication: An overview Ashwinkumar V. Meru ∗ , Shivani Mittra, Baskaran Thyagarajan, Anita Chugh New Drug Discovery Research, Department of Pharmacology, Ranbaxy Laboratories Limited, R&D, Plot 20, Sector 18, Udyog Vihar Industrial Area, Gurgaon 122001, Haryana, India Received 2 May 2005; received in revised form 26 October 2005; accepted 20 November 2005 Available online 28 December 2005 Abstract Intermittent claudication (IC) is defined by leg muscle pain, cramping and fatigue brought on by ambulation/exercise; relieved on rest; and caused by inadequate blood supply and is the primary symptom of peripheral arterial disease (PAD). PAD has a detrimental effect on the quality of life. PAD is a debilitating atherosclerotic disease of the lower limbs and is associated with an increased risk of cardiovascular morbidity and mortality. IC is an extremely important marker of atheroma. Up to 60% patients with IC have significant underlying coronary and/or carotid disease and 40% of all patients suffering from IC die or suffer a stroke within 5 years of presentation. The therapeutic intervention of IC essentially aims at providing symptomatic relief and reducing the systemic cardiovascular complications. Although exercise therapy is one of the most efficacious conservative treatments for claudication, the pharmacotherapeutic goals can be best achieved through an increase in the walking capacity to improve quality of life and a decrease in rates of amputation. In the development of treatment for IC, an aggressive non-pharmacological intervention and pharmacological treatment of the risk factors associated with IC are considered. In the next 2 years, the results of major trials of drugs that stabilize and regress atherosclerosis such as statins and angiotensin converting enzyme inhibitors, and anti-platelet agents, recombinant growth factors and immune modulators will be available for IC. Levocarnitine (l-carnitine) and a derivative, propionyl levocarnitine, are emerging agents that increase the pain-free walking and improve the quality of life in IC patients by working at the metabolism and exercise performance of ischemic muscles. This article provides a comprehensive review of the pathophysiology involved, diagnosis of IC and existing and emerging pharmacotherapies with rationale for their use in its treatment. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Intermittent claudication; Peripheral arterial disease; Pathophysiology; Risk factors; Pharmacotherapy Contents 1. Introduction ........................................................................................................ 222 2. Diagnosis .......................................................................................................... 223 3. Risk factors for intermittent claudication .............................................................................. 224 4. Pathophysiology of “IC” ............................................................................................ 225 5. Epidemiology/prevalence ............................................................................................ 226 6. Pharmacotherapy ................................................................................................... 228 6.1. Existing pharmacotherapy for intermittent claudication ........................................................... 228 6.1.1. Aspirin .............................................................................................. 228 6.1.2. Pentoxifylline ........................................................................................ 229 6.1.3. Cilostazol ........................................................................................... 229 6.1.4. Buflomedil .......................................................................................... 230 6.1.5. Naftidrofuryl ......................................................................................... 230 ∗ Corresponding author. Tel.: +91 124 5195277; fax: +91 124 2343545. E-mail addresses: ashwinkumar.meru@ranbaxy.com, ashwinmeru@yahoo.com (A.V. Meru). 0021-9150/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2005.11.027