Supervised Exercise Plus Angioplasty Best for Intermittent Claudication: Meta-analysis

(UPDATED) The biggest gains in walking distance among patients with intermittent claudication are seen with the combined use of angioplasty and supervised exercise therapy on top of best medical therapy, making that the preferred strategy in this population, authors of a new network meta-analysis conclude.

Through a year of follow-up, angioplasty plus supervised exercise therapy was associated with a 290-meter greater maximum walking distance compared with medical therapy alone and a 110-meter greater distance compared with supervised exercise, according to researchers led by Athanasios Saratzis, MBBS, PhD (Guy’s and St Thomas’ NHS Foundation Trust, London, England).

The findings, published online May 29, 2019, ahead of print in JACC: Cardiovascular Interventions, “have important implications for clinical practice,” they say.

“All patients with intermittent claudication should be offered best medical therapy, given the overwhelming evidence that [it] prevents future cardiovascular events and improves limb-related outcomes,” the investigators advise. “Adjunctive treatment modalities such as supervised exercise therapy and percutaneous angioplasty should, however, be also considered, to improve walking distance and quality of life.”

But they go even further, stating that this meta-analysis “strongly suggests that supervised exercise therapy with percutaneous angioplasty should be the preferred first-line treatment (always in the context of best medical therapy), followed by supervised exercise therapy (with best medical therapy). Offering percutaneous angioplasty without supervised exercise therapy should be avoided where possible.”

Mary McDermott, MD (Northwestern University Department of Medicine, Chicago, IL), who wrote an editorial accompanying the study, said that conclusion goes too far.

“I would be cautious about the interpretation of the meta-analysis because the authors’ conclusion implies that everybody should be getting revascularization, but the fact is that many patients with PAD aren’t eligible for revascularization because of the nature of their disease,” she commented to TCTMD, pointing out that revascularization “is not really a durable treatment” in many patients either. “But everybody should be advised to exercise,” McDermott urged.

Saratzis et al note that prior randomized trials have evaluated the relative merits of angioplasty and exercise interventions with best medical therapy and say that even though there have been meta-analyses, none have incorporated all possible treatment combinations or all quality-of-life data.

In an emailed comment, Saratzis and the two senior authors—Hany Zayed, MD (Guy’s and St Thomas’ NHS Foundation Trust), and Konstantinos Katsanos, MD, PhD (Patras University Hospital, Greece)—said that this analysis “is one of the most comprehensive literature syntheses in intermittent claudication to date and the first to employ a network meta-analytical approach. It confirms the central role of supervised exercise therapy (in addition to best medical therapy) in the treatment of claudicants, with or without undergoing revascularization in the form of an angioplasty.

“These patients, however, will receive the maximum potential benefit if they are offered all three treatment modalities combined (medical therapy + supervised exercise + angioplasty),” they continued. “Hopefully, physicians caring for claudicants will use these important findings to set up clinical services that can provide supervised exercise therapy in more areas, therefore benefiting patients in terms of both walking distance and quality of life.”

Exercise and Angioplasty Better in Combination

The investigators performed a network meta-analysis—which combines both direct and indirect comparisons between treatments—that incorporated 37 RCTs with a total of 2,783 patients who had intermittent claudication (mean weighted age 68 years; 54.5% men).

Patients were divided into four groups (all received best medical therapy):

• 688 received no additional interventions
• 1,189 underwent supervised exercise therapy
• 511 underwent percutaneous angioplasty
• 395 underwent both angioplasty and supervised exercise therapy

Exercise therapy, which mostly involved walking on a treadmill, lasted an average of 24 weeks, with an average of three sessions per week.

After a mean follow-up of 12 months, the maximum walking distance gain compared with medical therapy alone was greatest with angioplasty plus supervised exercise therapy, followed by exercise therapy alone and then angioplasty. The combined intervention also tended to have the greatest benefits in terms of quality of life, although the gains were not significantly greater when compared with supervised exercise therapy.

Exercise is amazingly effective, but the problem is it’s not a pill that you can take and get better overnight. You really have to stick with it. Mary McDermott

McDermott said the analysis doesn’t really change the understanding of the relative merits of supervised exercise therapy or angioplasty in this patient population. “It really confirms some other trials that have shown this phenomenon: if you undergo both revascularization and exercise, then that’s better than receiving either individual therapy,” she said.

The approach currently outlined in practice guidelines is the right strategy for incorporating supervised exercise therapy and angioplasty into treatment plans, according to McDermott. Guidelines state that all patients with PAD should first try supervised exercise therapy, and then if that doesn’t work, revascularization can be considered.

“There’s no question that people with certain types of disease respond better to revascularization,” McDermott acknowledged. “People who have a proximal stenosis, particularly an isolated stenosis, respond better, while those who have more distal disease or disease that’s closer to the knees or below the knees tend not to respond as well.”

Even though supervised exercise therapy should be tried first, it can be difficult to get patients into these programs, she said. Going in for supervised exercise can be burdensome, particularly for patients with intermittent claudication, many of whom are older and frail. Exercise can also be painful in this population, making it hard to get people to stick with it. And systemic issues come into play as well, as there is a lack of rehabilitation centers around the country, possibly related to the “somewhat modest” reimbursement provided by the Centers for Medicare & Medicaid Services (CMS) for these programs, McDermott said.

Several things might help improve the situation, she said. First, more resources and attention should be devoted to home-based exercise, which has been shown in some trials to improve walking performance in patients with PAD. Second, more resources should be directed toward helping patients get to supervised exercise programs. And third, additional education of both patients and healthcare professionals might pay dividends.

“Patients need to understand the benefits that exercise can bring them, and clinicians probably should be educated, too, that this is now covered by CMS—which is relatively new—and it really benefits the patients,” McDermott said.

This is particularly important because there aren’t a lot of therapies available for PAD, she noted.

“Exercise is amazingly effective, but the problem is it’s not a pill that you can take and get better overnight. You really have to stick with it, and I think that’s something that patients need to be educated about,” McDermott said. “And revascularization works for many patients and it does work overnight—you get the procedure and you can immediately walk better—but it’s really not a durable solution. It’s for many people only temporary, and for those who aren’t eligible for it because their disease anatomy is not well suited to it need help to be able to exercise regularly. So there’s still a lot of work we need to do.”