Objectives

To compare the effectiveness of aortic stent surgery versus exercise therapy in individuals with aortoiliac insufficiency.

Background

Peripheral arterial disease (PAD) is a major source of morbidity and mortality, particularly in older individuals. Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Despite its high prevalence, clinicians often fail to diagnose PAD, particularly in patients who do not have classic claudication symptoms. Although there is a growing body of literature demonstrating the value of exercise rehabilitation in individuals with PAD and claudication, exercise rehabilitation is not often prescribed as it 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.

At the time of the CLEVER trial, the use of surgical intervention and stent placement to improve blood flow in patients who did not have ischemic pain at rest or limb-threatening ischemia was controversial. There was data suggesting that patients with intermittent claudication who had revascularization with stents have improved exercise capacity and walking times.

Thus the CLEVER trial was initiated to compare the benefits of optimal medical therapy, structured exercise, and stent revascularization on both walking outcomes and measures of quality of life in patients with claudication due to aortoiliac PAD.

Participants

The study population consisted of individuals with symptoms of moderate to severe intermittent claudication (defined as ability to walk at least 2, but not more than 11, minutes on a graded treadmill test using the Gardner protocol) and objective evidence of a hemodynamically significant aortoiliac arterial stenosis. Individuals with critical limb ischemia or who had comorbid conditions that limited their walking ability were excluded. A total of 119 participants were enrolled and randomized.

Design

The broad objective of the CLEVER study was to optimize physical functioning, increase activity levels, and reduce cardiovascular disease risk in older individuals with PAD. The specific aim of the trial was to test the primary hypothesis that aortoiliac stenting/pharmacotherapy improves maximum walking duration better than supervised exercise rehabilitation/exercise maintenance/pharmacotherapy for those with aortoiliac artery obstruction at 6 months.

Participants were evaluated at baseline and 6 months. Demographic data, anthropomorphic and physiologic variables, atherosclerosis risk factors (lipid profile, HbA1c), and inflammatory biomarkers (plasma fibrinogen, C-reactive protein) were assessed. Participants were asked to wear pedometers during all waking hours for a seven-day period between the two baseline treadmill tests. Participants completed generic and disease-specific quality of life surveys, and Peripheral Artery Questionnaire.

This study evaluated distinct strategies of care in three treatment groups: optimal medical care (OMC), supervised exercise rehabilitation (SE), and stent revascularization (ST). A fourth treatment group that combined ST and SE was dropped after enrolling 8 participants upon the recommendation of the Data Safety and Monitoring Board. Optimal medical care was established via active promotion of the standards established by intersocietal 2005 ACC-AHA Guidelines. All study participants received cilostazol 100 mg by mouth twice daily as tolerated. Supervised exercise consisted of 26 weeks of exercise, three times a week, for an hour at a time. Stent revascularization was done to relieve all hemodynamically significant stenoses (>50% by diameter) in the aorta and iliac arteries using self-expanding or balloon-expandable stents.

Participants were called monthly to inquire about adverse events; at three months to refill their cilostazol medication; and at six months to undergo the same testing as at baseline, except that the treadmill test was performed only once at the six month outcome evaluation.

The primary endpoint was the change in peak walking time on a graded treadmill test at 6 months as compared with baseline. Secondary endpoints included free-living step activity, quality of life using the Walking Impairment Questionnaire and Peripheral Artery Questionnaire, and cardiovascular risk factors.

Conclusions

Supervised exercise resulted in superior treadmill walking performance as compared to stent placement, even for those with aortoiliac peripheral artery disease.

Circulation. 2012 Jan 3; 125(1): 130–139.

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