CLEVER! Exercise Better Than Stenting in Proximal PAD

November 16, 2011

November 16, 2011 (Orlando, Florida) — Adding a supervised exercise program to optimal medical care can improve walking performance better than performing stent revascularization in patients with symptomatic aortoiliac peripheral artery disease (PAD), a small randomized trial suggests [1].

The multicenter Claudication: Exercise versus Endoluminal Revascularization (CLEVER) trial is the first of its kind "to examine the relative benefit of supervised exercise, stenting, and optimal medical care and the first trial conducted exclusively in patients with aortoiliac PAD, long considered ideal for stent revascularization," according to Dr Timothy P Murphy (Rhode Island Hospital, Providence) and colleagues, in their report published online today in Circulation.

Dr Alan T Hirsch

As described by Dr Alan T Hirsch (University of Minnesota, Minneapolis), who presented the CLEVER results to the media here at the American Heart Association 2011 Scientific Sessions, stenting "has a track record of great efficacy" in patients like those in CLEVER, who were "rather ill" with hemodynamically significant aortoiliac PAD, moderate to severe claudication, and low ankle-brachial index readings. "It's also notable that, at least in North America, stent procedures are reimbursed, [and] supervised exercise is not," Hirsch noted.

But the six-month results of CLEVER, he said, suggest that "supervised exercise in fact offers better treadmill walking performance than stent revascularization alone," although both therapies are "effective" and superior to standard medical care alone.

Indeed, the CLEVER paper concludes that the effectiveness of both interventions in the trial "provide widened choices for all patients." The "ideal treatment," it states, will depend on patient preference. "At the very least, the CLEVER six-month results suggest that supervised exercise is a reasonable strategy compared with stenting and that efforts should be made to develop supervised exercise programs that are available and affordable to patients."

On the other hand, according to Dr Michael S Conte (University of California, San Francisco), the scheduled discussant following the CLEVER live presentation, the trial also suggests that "optimal medical care appears to have little clinical benefit." It seemed to make a relatively modest improvement on patients' walking performance, he noted in his presentation for the media, "and it agrees with what we've observed in clinical practice."

Dr Michael S Conte

CLEVER randomized 111 patients with symptomatic aortoiliac PAD, at 22 sites in Canada and the US, to one of three regimens: optimal medical care on its own or with either a supervised exercise program or stent revascularization.

Optimal medical therapy included cilostazol (Pletal, Otsuka America) 100 mg twice daily, with "prescription of a classic home walking program, supported by a nurse coordinator who would call the patients and verify that they understood the need for walking," Hirsch said. Supervised exercise consisted of exercise according to a single studywide protocol, for one hour, three times per week, for 26 weeks. Stenting was aimed at treating all hemodynamically significant >50% stenoses in the aorta and iliac arteries.

The change in peak walking time from baseline to six months, the primary end point, "was minimal in the optimal-medical-care group, a 1.2-minute improvement, which was dwarfed by [improvements] in the two active-treatment groups," Hirsch noted.

Changes in Functional Measures From Baseline to Six Months by Management Group

End point OMC+supervised exercise, n=38 (min) OMC+stenting, n=41 (min) OMC, n=20 (min) p, supervised exercise vs OMC p, stenting vs OMC p, supervised exercise vs stenting
Change in PWT 5.8 3.7 1.2 <0.0001 0.021 0.042
Change in COT 3.0 3.6 0.7 0.003 0.006 0.425

OMC=optimal medical care; PWT= peak walking time; COT=claudication-onset time

Disease-specific quality of life, as measured by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire, improved for both exercise and stenting compared with optimal medical care for most of their domains, including pain severity, symptoms, walking distance and speed, and social limitation. But, note Murphy et al, "the greatest improvements in self-reported quality of life were observed in the stenting cohort." That apparent inconsistency is unexplained and should be explored further, they write.

"It's unclear whether these results will actually alter the perceptions of clinicians," according to Conte. Supervised exercise emerged as an effective if not better alternative than stenting, but "the apparent discordance between the treadmill outcome and quality of life limit the trial's potential impact on practice, I believe."

And any impact is unlikely, he said, unless reimbursement policies change. "I think at this point, with all the evidence we've had to date, it's striking that reimbursement for supervised exercise is still not available to Medicare beneficiaries, which are most of the patients with peripheral artery disease. In contrast, reimbursement for stenting to providers is significant [but] has not been linked to outcomes--and both providers and industry are incentivized to provide invasive treatments. We need to increase pressure on [the Centers for Medicare & Medicaid Services] CMS to provide reimbursement for supervised exercise."

CLEVER was "mostly" funded by the National Heart, Lung, and Blood Institute and also was supported by Cordis/Johnson & Johnson, eV3, Boston Scientific, and Otsuka America. Murphy has received research grant support from Abbott Vascular, Cordis/Johnson & Johnson, and Otsuka Pharmaceuticals and consultant fees from Microvention/Terumo. Hirsch discloses grant support from Cytokinetics, Viromed, and Abbott Vascular and consulting fees from Merck, Pozen, Novartis, and AstraZeneca. Disclosures for the coauthors are listed in the paper.


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