Author + information
- Piotr S. Sobieszczyk, MD and
- Joshua A. Beckman, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Joshua A. Beckman, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Intermittent claudication is the most common symptomatic form of peripheral artery disease (PAD). The magnitude of the disability from claudication is severe, such that patients report a marked decrease in their quality of life (1). Despite vigorous investigative efforts, only 4 treatments reliably reduce disability and increase walking distance: cilostazol; exercise training; percutaneous angioplasty and stenting; and surgical bypass. Cilostazol, an oral phosphodiesterase-3 inhibitor, modestly increases walking distance and rarely returns patients to full functional status (2). Therapies currently recommended most to relieve intermittent claudication include exercise training and percutaneous revascularization. In multispecialty expert consensus guidelines released in 2005 and reaffirmed in 2011, supervised exercise training is the recommended initial treatment modality for patients with intermittent claudication, with endovascular revascularization reserved for patients who have failed exercise therapy or have a “very favorable risk-benefit ratio” (3).
Despite wide agreement of the value of supervised exercise therapy, endovascular therapy has become, de facto, the only treatment in the management of patients with claudication that is due to aortoiliac arterial disease, despite a paucity of clinical trials supporting its durability and long-term impact on patients’ functional status. There are several obvious reasons why endovascular therapies are commonly chosen. First, when successful, they make patients feel better quickly. Second, the time required for the treatment is short. Third, exercise therapy is labor intensive, requiring a significant investment of time and effort by the patient and team of healthcare providers, making the process challenging (4). Fourth, and likely most important, only endovascular therapy is reimbursed in the United States. Thus, despite a rich database demonstrating the value of supervised exercise rehabilitation (5), it is not routinely prescribed because it is neither reimbursed nor available. Fifth, the benefits after cessation of the training program are unclear (6,7). Thus, at least in part because of a lack of available options, patients and providers have gravitated to endovascular intervention as the first-line therapy for intermittent claudication caused by aortoiliac occlusive disease.
To clarify the value of available therapies for claudication, Murphy et al. (8) performed the CLEVER (Claudication: Exercise Versus Endoluminal Revascularization) study. This multicenter, National Heart, Lung, and Blood Institute–sponsored trial compared the outcomes of the 3 recommended therapies in patients who experienced moderate-to-severe claudication caused by aortoiliac occlusive disease: 1) contemporary pharmacotherapy and advice to exercise (optimal medical care [OMC]); 2) endovascular intervention and OMC; and 3) supervised exercise and OMC. Interventional therapy involved treatment of all aortoiliac stenoses >50%. The exercise arm involved hour-long sessions performed 3 times a week for 26 weeks. After completing the training program, patients were provided counseling by telephone, promoting exercise and preventing relapse. The 6-month results of this trial were previously published and showed improved walking times for both supervised exercise and endovascular revascularization (8). The exercise arm had a significantly greater peak walking time than the stenting arm, whereas the stenting arm had a significantly greater increase in quality of life than the exercise arm. Whether 6 months of exercise therapy would provide a durable result comparable to endovascular therapy remained speculative.
In this issue of the Journal, Murphy et al. (9) report the 18-month results of the CLEVER trial. At 18 months, both supervised exercise and endovascular therapy yielded a superior functional capacity compared with OMC. The peak walking time and claudication onset time improved from baseline and remained significantly longer among patients treated with exercise or stenting than in the OMC arm. Perhaps surprisingly, there was no longer a difference between the 2 active arms: both parameters of walking capacity improved and remained similar for 18 months, although this may be a function of the number of patients available for follow-up. Quality of life, measured by the disease-specific quality-of-life metrics (Walking Impairment Questionnaire and Peripheral Artery Questionnaire), remained significantly higher in the exercise and intervention groups compared with the OMC arm.
The trial team must be congratulated for completing this labor-intensive project, conducted in 29 centers over the course of 4 years. They enrolled 111 patients, and only 79 completed the 18-month program, although the baseline characteristics of patients unavailable for follow-up were similar to those who continued participation. These numbers highlight some challenges in comparing therapies in an environment in which 1 therapy is dominant because of perception of benefit, established reimbursement, and instant gratification. They also limit the generalizability of the results. Is it possible that many patients with aortoiliac disease were not considered for enrollment because endovascular therapy was considered routine, and those enrolled represented a more complex group with less certain benefit of intervention? It is shameful that we in the vascular community cannot muster sufficient effort and interest, even when resources are provided, to enroll meaningful numbers of patients in a trial like the CLEVER study (10).
Several important points can be gleaned from this trial. First, both exercise training and endovascular therapy are durable. The subjects’ adherence to exercise therapy is notable: 71% attended at least 70% of the scheduled sessions, and 88% continued to participate in the telephone counseling program. One surmises that the sustained benefit of exercise was, in large part, due to motivated subjects who continued to exercise while supported remotely by determined study staff. Recent data suggest that telephone-based support may be a viable option in getting PAD patients to exercise (11). However, it is not certain whether such a well-organized training and support system can be broadly reproduced and applied.
Second, both therapies are effective in patients with intermittent claudication from aortoiliac occlusive disease. The current paradigm favors a quick and moderate improvement in walking distance with a significant improvement in quality of life at the expense of significantly greater increase in walking distance. The lack of reimbursement for exercise therapy is particularly distressing, for it presumes that “1 size fits all.” This is particularly irksome, because exercise has ancillary benefits, with reductions in blood pressure, improvements in the lipid profile, and better glucose control—all standard recommendations for patients with atherosclerosis. We strongly advocate research to identify patients for whom one therapy would be recommended first over the other.
Third, it is time to end the competition between therapies. This well-done trial makes clear that supervised exercise and percutaneous revascularization have different mechanisms of action and different treatment outcomes—both of which are desirable. In contrast to pitting one treatment against the other, it might be better to treat claudication like hypertension, where practitioners use as many therapies as needed to bring the patient to goal. The goal in patients with claudication is to minimize (to 0 if possible) the disability caused by claudication. Cilostazol, supervised exercise therapy with follow-up telephone monitoring, and endovascular revascularization are complementary, should be used as needed in appropriate patients, and applied until the patient is better.
A final observation is that the trial evaluated a therapy currently unavailable in the United States. The CLEVER trial established that supervised exercise is at least as effective as endovascular intervention. Despite the existing infrastructure for cardiac and pulmonary rehabilitation programs, exercise therapy remains unavailable for patients with PAD and intermittent claudication, even though it is less expensive than intervention (12). The demonstration that the results are durable in patients with claudication in the CLEVER study should spur a change in coverage by federal and private insurers to make supervised exercise therapy and follow-up care available to all patients who need them.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Beckman has consulted for Bristol-Myers Squibb, AstraZeneca, Merck & Co., and Novartis; has an investigator-initiated research grant from Bristol-Myers Squibb; and is a member of the Board of Directors of VIVA Physicians. Dr. Sobieszczyk has reported that he has no relationships relevant to the contents of this paper to disclose.
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