November 12, 2012

LOS ANGELES — A program of supervised exercise for 30 minutes, twice a week, was as effective as endovascular revascularization in terms of functional outcomes and quality of life in patients with intermittent claudication, according to a randomized controlled study reported at the American Heart Association (AHA) 2012 Scientific Sessions last week.

Dr Farzin Fakhry

In addition, the improvement seen with both interventions was sustained out to seven years, Dr Farzin Fakhry (Erasmus Medical Center, Rotterdam, the Netherlands) told the meeting. Moderator of the session, Dr Sue Duval (University of Minnesota, Minneapolis), said: "These are impressive data for seven years, given the relatively short intervention." The other moderator, Dr Joshua A Beckman (Brigham and Women's Hospital, Boston, MA), added: "Dr Fakhry has really raised the bar on doing single-center research in peripheral arterial disease [PAD]--you will all remember the CLEVER study published by the [National Institutes of Health] NIH, and it had fewer patients than his study did.

"First, I want to compliment Dr Fakhry for showing us that exercise may actually have very long-term benefits in terms of patient function, even if it wasn't established in his group that they have reductions in mortality," Beckman continued.

Where we are moving is to figure out what the combination of therapies is that is most appropriate for each individual patient.

"When it comes to what is the best therapy for claudication, it's like trying to ask what's better, eating an apple or a pear? The methods by which revascularization work are not the same as the methods by which medical therapy and exercise work. I'm pretty sure they are going to be complementary when anyone is able to gather enough patients to make that clear. I think where we are moving is to figure out not necessarily what is the single best strategy to make people feel better, but what the combination of therapies is that is most appropriate for each individual patient."

SET Therapy First Regimen Should Be Treatment of Choice in Intermittent Claudication

Fakhry told the meeting that pharmacotherapy "is of limited effectiveness" in patients with intermittent claudication, a symptomatic form of PAD constituting pain in the thigh or calf muscle that limits exercise. While supervised exercise treatment (SET) is the first-line recommended therapy in international guidelines, "We see from clinical practice that endovascular revascularization is increasingly preferred," Fakhry observed.

In his trial, 150 patients with intermittent claudication were randomized to either SET, which involved walking on a treadmill for 30 minutes twice a week (n=75), or endovascular revascularization (n=75). Baseline characteristics of the patients were similar, he noted. Patients in both groups were advised to walk at home as much as possible.

Outcome measures included functional performance--including maximal walking distance, pain-free walking distance, and ankle-brachial index--and events--secondary interventions (endovascular or surgical), minor or major amputations, and death. They also measured quality of life, including VascuQol and SF-36.

The one- and seven-year results indicate that SET and endovascular revascularization were "equally effective in improving functional performance and quality of life," Fakhry said. The study had 36 patients in the exercise group and 47 in the revascularization group who were available for the longer follow-up of seven years, he noted.

The number of patients with one or more secondary interventions was higher in the SET group (32 patients underwent at least one secondary intervention compared with 17 in the endovascular-revascularization group; p=0.01), although the average number of secondary interventions did not differ between the groups (2.0 in the SET group vs 2.8 in the revascularization group [p=0.10]). Two patients in the exercise group underwent minor amputation, and three in the revascularization group had a major amputation.

"The study supports the use of a SET-first treatment regimen in the care of patients with intermittent claudication," Fakhry concluded.

Beckman told heartwire that while supervised exercise therapy "would be everybody's first choice" and is indicated as such in most guidelines, in the US, at least, it is not reimbursed, so this severely limits the use of this treatment.

Trials Lacking in PAD, But Most Need Exercise and Intervention

Commenting further, Beckman said: "The real crime in this field is that we can't recruit enough people in studies when we know there are tens of thousands, if not millions, of people with the condition. In the US, the entrepreneurial motive in taking care of patients basically prevents the adequate inclusion of patients in clinical trials, and it is ridiculous that we couldn't enroll more than 150 patients [in CLEVER] over several years, considering that PAD interventions cost more to the US economy in 2011 than coronary artery disease interventions--$4 billion vs $3 billion."

The real crime in this field is that we can't recruit enough people in studies when we know there are tens of thousands, if not millions, of people with the condition.

That said, he adds that "trying to figure out the best first therapy for intermittent claudication is, in my opinion, the wrong way to look at this. I would look at who are the patients who are likely to derive benefit from any of the therapies that we apply. My guess is that, over time, we are going to figure out a stepwise approach, so that we can, for example, put people on supervised exercise and if that works, great, and if it doesn't work, we may add on intervention. Or we may find out that if we start people on intervention first they feel so much better that they are much more willing to participate in exercise therapy."

Ongoing Research to Identify Asymptomatic PAD Patients

Dr Joshua A Beckman

And Beckman says that despite the paucity of clinical-trial data in the field of intermittent claudication, he is impressed by the research in general that is ongoing in noncoronary vascular disease. "The common theme is what we can do to figure out the patient who is at high risk, before they know they have a problem. This is likely to be a very fruitful pathway to make a person feel better and live longer before they have the event that's going to end their lives.

"We have made great strides over the past couple of decades in that the event rates for everything are down, including amputations in patients with diabetes and PAD. So although we don’t necessarily have agreement on what is the single best method to find out who is at high risk, it is the ongoing work where we can begin to ferret out what's real and what's nice to look at but may not add much to the management of patients."