Claudication: Exercise Versus Endoluminal Revascularization (CLEVER)

BACKGROUND: Peripheral arterial disease (PAD) is a major source of morbidity and mortality, particularly in older individuals. Despite its high prevalence, clinicians often fail to diagnose PAD, particularly in patients who do not have classic claudication symptoms. Even in those individuals with documented PAD, cardiac risk factors are not often aggressively treated, and only a minority of patients receive pharmacologic therapy with cilostazol. Although there is a growing body of literature demonstrating the value of exercise rehabilitation in individuals with peripheral vascular disease and claudication, exercise rehabilitation is not often prescribed as supervised exercise rehabilitation for claudication, is not reimbursed by Medicare, and is rarely covered by private insurance. Therefore, few individuals with PAD and intermittent claudication have access to supervised exercise rehabilitation. The use of surgical intervention and stent placement to improve blood flow in patients who do not have ischemic pain at rest or limb-threatening ischemia (Fontaine class III or IV) remains controversial. There is data suggesting that patients with intermittent claudication who have had revascularization with stents have improved exercise capacity and walking times. However, the patients in the various studies often differ substantially in their clinical characteristics, and a variety of techniques were employed, including balloon angioplasty and stents, which makes it difficult to come to a definitive conclusion about the relative efficacy of stenting to improve functional performance. Additionally, to our knowledge, the combination of stent revascularization with supervised exercise rehabilitation has not been studied. DESIGN NARRATIVE: The broad objective of the study is to optimize physical functioning, increase activity levels, and reduce cardiovascular disease risk in older individuals with PAD. The specific aim of the trial is to test the primary hypothesis that aortoiliac stenting/pharmacotherapy improves maximum walking duration (MWD) better than supervised exercise rehabilitation/exercise maintenance/pharmacotherapy for those with aortoiliac artery obstruction at 6 months. Other aims are to compare these two treatment groups with two other treatment groups, optimal medical care/pharmacotherapy and combined stent plus supervised exercise rehabilitation, at 6 months, and to compare all 4 groups with regard to the following variables: MWD change score at 18 months, changes in free-living daily activity levels, patient-perceived quality of life (QoL), and cost-effectiveness. The study also will perform exploratory analyses of demographic and biochemical risk factors for atherosclerosis, including body mass index (BMI), blood pressure, lipid profile, hemoglobin Alc (HgbAlc), fibrinogen, and C-reactive protein. An estimated 252 patients (at up to 30 study sites) with aortoiliac insufficiency and intermittent claudication will be randomly divided into four groups: optimal medical care/pharmacotherapy, supervised exercise rehabilitation/maintenance/pharmacotherapy, stent/pharmacotherapy, and stent/supervised exercise rehabilitation/pharmacotherapy. Recruitment will be performed over 28 months and patients will be followed for 18 months; the total study duration will be 5 years.