ORLANDO – In patients with aortoiliac peripheral artery disease, adding supervised exercise to optimal medical therapy offers better treadmill walking performance than does aortoiliac stenting.
On the other hand, aortoiliac stenting plus optimal medical care results in better quality of life than does supervised exercise, according to the 6-month results of the CLEVER (Claudication vs. Endoluminal Revascularization) trial.
The CLEVER trial produced discordant results at 6 months, but also a clear signal that the combination interventions are superior to optimal medical therapy alone.
"This idea that you can go home and walk isn’t, and hasn’t been, effective," coauthor Dr. Alan Hirsch said at the annual scientific sessions of the American Heart Association.
CLEVER is the first prospective, head-to-head, comparative trial of three guideline-recommended interventions: supervised exercise, stenting, and optimal medical therapy. It is also the first trial to be conducted exclusively in patients with aortoiliac peripheral artery disease, a group generally considered ideal for stent revascularization, he said.
CLEVER randomized 111 patients to either optimal medical care, (OMC) including cilostazol (Pletal) 100 mg twice daily, plus advice about home exercise and diet with monthly coordinator contact; OMC plus supervised exercise for 1 hour thrice weekly for 26 weeks; or OMC plus aortoiliac stenting. All patients had moderate to severe claudication.
The patients averaged 64 years of age. Their baseline ankle-brachial index was 0.68, peak walking time was about 5 minutes, and claudication-onset time was 1.5 minutes.
The primary end point of change in peak walking time from baseline to 6 months was just 1.2 minutes in the OMC group, compared with 5.8 minutes in the supervised exercise group and a clinically significant 3.7 minutes in the stenting group, said Dr. Hirsch, director of the vascular medicine program at the University of Minnesota in Minneapolis. The changes were significantly different between supervised exercise and OMC (4.6 minutes), stenting and OMC (2.5 minutes), and supervised exercise and stenting (2.1 minutes).
The change in claudication-onset time from baseline to 6 months was again low with OMC at just 0.7 minutes, compared with 3 minutes with the supervised exercise and 3.6 minutes with stenting. The changes were significantly different between supervised exercise and OMC (2.2 minutes) and stenting, compared with OMC (2.9 minutes), but not between supervised exercise and stenting (0.7 minutes), again suggesting the similarity of the two interventions, he said.
Self-reported quality of life scores on the Walking Impairment Questionnaire and Peripheral Artery Questionnaire improved significantly with supervised exercise plus stenting, compared with OMC for most domains including walking distance, walking speed, stair climbing, physical limitation, social limitation, and summary score. The improvements were significantly greater with stenting than with supervised exercise for three of the four domains that were evaluated on each questionnaire.
Dr. Hirsch said the quality of life finding raises questions that CLEVER was not designed to answer, and he hoped the trial would inspire future research. Ongoing 18-month follow-up is expected to provide greater insight into the relative durability of the treatments, as well as the health economic impact.
Dr. Conte added that reimbursement for stenting is significant and not linked to outcomes, and providers and industry are therefore incentivized to provide invasive treatments.
He called for greater investment in clinical trials in PAD, more trials in intermittent claudication to clarify the best outcome measures that correlate with patient improvement in everyday life, increased pressure on the Centers for Medicare and Medicaid Services to provide reimbursement for supervised exercise programs, and more effective pharmacotherapies in intermittent claudication.
The study, which was led by Dr. Timothy Murphy, medical director of the vascular research center at Brown University in Providence, R.I., was simultaneously published online (Circulation 2011 Nov.16 [doi:10.1161/circulationaha.111.075770]).
The National Heart, Lung, and Blood Institute funded the trial, with additional support from Cordis/Johnson & Johnson, eV3, Boston Scientific, and Otsuka America. Dr. Hirsch reported grant support from Abbott Vascular, Cytokinetics, and Viromed, as well as having consulted for AstraZeneca, Merck, Novartis, and Pozen. Dr. Conte reported that he had no relevant disclosures.