Lessons Learned from Recent Randomized Clinical Trials for Intermittent Claudication

It is well recognized that lower extremity peripheral arterial disease (PAD) is highly prevalent and results in significant cardiovascular mortality akin to cardiovascular disease.1 Among patients with PAD there is a broad range of clinical manifestations, with a third of patients having typical intermittent claudication (IC). The symptoms of lower extremity PAD, even in a stable nonlimb threatening form, result in measurable reductions in quality of life (QOL) and physical functioning, including mobility loss.2 The morbidity from PAD and relatively high rate of vascular procedures performed in symptomatic patients has resulted in health economic costs that are greater than ischemic heart disease and stroke.3 Moreover, the number of catheter-based interventions for PAD has increased in recent years, likely due to multiple factors, including disease recognition, development of endovascular devices, and a shift from open surgical procedures and performance of procedures by 3 disciples of medicine: interventional cardiology, interventional radiology, and vascular surgery.4,5One of the major unresolved issues is how should outcomes be measured? Is it enough to improve QOL or do we need to demonstrate reductions in cardiovascular morbidity and mortality to justify the cost of invasive therapies? In 2007, over 2 million physician office visits were related to PAD; therefore, performing clinical trials to study the treatment of PAD should be relatively straightforward, but unfortunately this has not been the case. Randomized clinical trials in PAD are uncommon and notoriously slow to enroll. This may be due to restrictive enrollment criteria, or to an unfounded belief of lack of clinical equipoise between randomized treatments that bias physicians and patients.6,7 That the pace of research in the field is slow is reflected in the fact that from the PAD guidelines in 2005 to the update in 2011, which included clinical …