Anti-platelet therapy: Is it all over in peripheral artery disease?

Abstract

Peripheral artery disease (PAD) is probably much more common and important than we perceive, ranging in prevalence from 6% among patients over the age of 55 years to 18% based of Caucasian European populations (1). The prevalence of PAD rises with age, to 20% in those over 70 and even up to 60% in those over 85 years old (2). Patients with PAD have a three-fold risk of myocardial infarction, stroke, or death from cardiovascular causes (3). PAD is also well associated with a high amputation risk and poor quality of life, especially affecting those with diabetes, therefore creating a substantial economic burden (4). The most recognised clinical manifestation of PAD is intermittent claudication of the lower limbs. This “pain” however intermittent is caused by ischaemia secondary to atherosclerotic arterial narrowing and is clearly a manifestation of systemic atherosclerosis (3). Indeed, a low ankle brachial pressure index (ABI) has been shown to be predictive of coronary heart disease and all-cause mortality (4) (relative risk 1.60;95% confidence interval [CI] 1.32–195) (5). Over a five-year period, those with an ABI ≤0.9 have a two-fold risk of a cardiovascular event compared to those with an ABI >0.9 (6). The Framingham Offspring Study in 1999 reported a PAD prevalence of 90% in those who undergoing coronary angiography (7). Yet, PAD remains the most undermanaged, underdiagnosed, and understudied of all manifestations of atherosclerotic disease. Known risk factors of other atherosclerotic disease are similar for PAD, and include age, smoking, high blood pressure and hyperlipidaemia. Disease risk factor modification studies have suggested that risk factor control itself is inadequate, and other therapeutic requirements are necessary in PAD. Other pathophysiological processes, such as low-grade inflammation may be involved, as the latter is independent risk factor for PAD (8, 9). Most recently, homocysteine, C-reactive protein, fibrinogen, lipoprotein, hypercoaguability and increased platelet activity have all been implicated as risk factors for atherosclerosis (10, 11). In PAD, the main pathological process of obstruction of the arteries is caused by atherothrombosis, embolism, arteritis, and aneurysms (12). Platelets play an important role in the process of thrombosis at the site of plaque formation (13). Platelet activation markers, such as soluble CD40 ligand and P-selectin (14) levels, have been increased in studies of patients with PAD (15, 16). Urinary 11-dehydrothromboxane B2 has also been found to be increased in PAD, implicating a further platelet component (13). The modern management of PAD is largely directed to symptom control but emphasis is directed mainly to prevention of systemic complications with ‘best medical therapy’, with percutaneous or surgical revascularisation being considered where optimised medical therapy fails. Indeed, the similarities between atherosclerotic risk factors and the role of platelets in both cardiovascular and cerebrovascular diseases have led to extensive extrapolation of evidence derived from coronary artery disease to PAD, for example, with regard to the use of anti-platelet agents (17, 18). In this issue of Thrombosis and Haemostasis, Basili et al. (19) report results of a meta-analysis of 29 clinical randomised trials on anti-platelet therapy in PAD, assessing their prevention of cardiovascular Correspondence to: Mr. A. S. Jaipersad University of Birmingham Centre for Cardiovascular Sciences City Hospital, Birmingham B18 7QH, UK E-mail: tonyjaipersad@btinternet.com