Outcomes for Clinical Studies Assessing Drug and Revascularization Therapies for Claudication and Critical Limb Ischemia in Peripheral Artery Disease

Abstract

Peripheral artery disease (PAD), which affects the large and medium arteries of the lower extremities, is a substantial cause of morbidity and health costs.1–5 Clinical studies assessing treatments for PAD guide clinical management but require standard definitions of disease and outcomes to ensure validity and consistency within and between studies. Prior guidelines for PAD outcomes in clinical trials were developed by consensus from stakeholders in multiple disciplines.6–8 They consider outcomes of medical therapies targeting systemic atherosclerosis and medical or surgical therapies for leg-specific symptoms such as claudication or critical limb ischemia. However, the rapid development of percutaneous technologies and the promise of new biological therapies (eg, cell-based therapies) expand treatment options and require a re-evaluation of important outcomes in clinical trials of PAD. Multidisciplinary consensus statements for other percutaneous treatments also provide insights to help develop standardized outcomes for trials of PAD. These include the Academic Research Consortium definitions for outcomes in percutaneous coronary interventions9 and the Valve Academic Research Consortium definitions of outcomes for transcatheter aortic valve replacement.10 Although this article is not meant to provide a definitive statement on outcomes for clinical trials on symptomatic PAD, it is designed to stimulate discussion toward a multidisciplinary consensus statement that embraces new percutaneous technologies and medical and surgical treatments for PAD. PAD is defined clinically by an abnormal ankle-brachial index (ABI) ≤0.90. 6,7,11 The ABI for each leg is measured with a Doppler probe and is the ratio of the highest systolic pressure from the dorsalis pedis or posterior tibial artery in a leg divided by the highest arm systolic pressure.11,12 Although there are other causes of PAD (eg, thromboembolic causes, inflammation, trauma, aneurysms, entrapment syndromes, adventitial cysts, congenital abnormalities),12 atherosclerosis is the predominant cause of PAD. Medical …