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Extracorporeal shockwave therapy may be effective for intermittent lower limb claudication in peripheral artery disease (PAD) patients unable to engage in supervised exercise or who experienced little benefit from that standard first-line approach, a randomized trial suggested.

For the primary endpoint, patients who received nine sessions of the electrical impulses to the gastrocnemius muscle over a 3-week period had significantly greater improvements in physical function versus a sham therapy, as measured by the Physical Functioning domain of the 36-item Short-Form questionnaire (SF-36).

At 12 weeks, a 3.8-point (95% CI 0.0-7.7, P=0.03) greater estimated median difference on the 100-point scale emerged for patients assigned to the shockwave therapy, reported researchers led by Paris Cai, MBBCh, BAO, of Hull York Medical School in England.

Furthermore, the shockwave group had significantly greater improvements at this time point in pain-free walking distance (median 34.1 meters, 95% CI 11.4-56.8, P=0.004) and maximum walking distance (median 51.4 meters, 95% CI 10.7-86.5, P=0.01), according to findings of the single-center double-blind study published in .

Despite a post hoc analysis showing the primary endpoint lost significance when adjusted for baseline differences in coronary artery disease, the research team nevertheless concluded that extracorporeal shockwave therapy "appears to be a potential alternative to supervised exercise for patients with intermittent claudication that can improve patient choice and increase access and engagement with noninvasive treatment."

Intermittent claudication is a common manifestation of PAD that is characterized by muscle pain during activity due to a lack of blood flow, typically to the lower extremities.

Beyond smoking cessation and other forms of cardiovascular risk reduction, "supervised exercise is the recommended first-line treatment for intermittent claudication but is generally met with poor uptake and completion rates as low as 25% and 75% respectively," according to Cai and co-authors. As such, other noninvasive treatment options are needed, they said.

Extracorporeal shockwave therapy, which delivers short-wave acoustic pulses and may induce angiogenesis in treated tissue, has been used in a number of conditions such as and even . But evidence for its effectiveness in PAD has been limited outside of , leading to the current first-of-its kind trial, which recruited patients from a tertiary center for vascular surgery.

"The aim of the intervention was not to eradicate claudication symptoms but to reduce them to enable patients to mobilize further," the researchers explained. "This means that there will be a continuing impact of intermittent claudication on quality of life."

No other secondary endpoints of the trial, which included ankle brachial pressure index and multiple other measures of quality of life, showed any between-group differences at 12 weeks, but some improvements favoring shockwave therapy were observed at earlier follow-ups.

In an , Helen Potter, MD, and Linda Harris, MD, DFSVS, both of the Jacobs School of Medicine and Biomedical Sciences in Buffalo, New York, raised a host of issues with the findings, including whether efficacy will be sustained after stopping the shockwave therapy sessions and whether adherence might be as low as with exercise therapy, given that the study protocol involved nine sessions over a 3-week period. Of note, approximately two-thirds of eligible participants declined to participate in the trial.

They also questioned why the investigators included two very distinct groups in the trial: patients unable to receive supervised exercise and those still symptomatic following an exercise program.

"While these preliminary findings are intriguing, it is too early to call the results efficacious with assessment only out to 12 weeks," wrote Potter and Harris. "It will be extremely important to assess midterm and long-term benefits from intervention with extracorporeal shockwave therapy, need for repeat interventions, and whether repeat interventions will continue to be efficacious before endorsing this technology as appropriate for patients with lifestyle-limiting but not limb-threatening disease."

Cai and colleagues identified 389 eligible patients for the trial, of which 138 agreed to participate and were randomized 1:1 to nine sessions over 3 weeks of the intervention or sham treatment. Patients were excluded if they had active cancer or were on anticoagulants.

Intervention participants received 100 impulses of 0.1 mJ/mm/cm² with the PiezoWave 2 shockwave system to the symptomatic calf muscle. The sham group underwent the same preparation for treatment, including the application of ultrasonography gel and having the transducer run over the affected area, but were given no impulses (a recording simulated delivery of the shockwaves).

At baseline, two-thirds of participants were male, the average age was 67 years, over 90% had a smoking history, and roughly 60% had hypertension. More patients in the sham arm had diabetes (36% vs 24% in the shockwave arm) and a history of coronary artery disease/ischemic heart disease (44% vs 32%). Overall, more than 90% had calf-exclusive claudication and about 10% had bilateral involvement.

Patients in the intervention and sham arms had median scores of 36.5 and 33, respectively, on the Physical Functioning domain of the SF-36 at the start of the trial. These increased to 41.3 and 34.6 at 12 weeks.

For the intervention arm, pain-free walking distance increased from 49 meters at baseline to 105.6 meters at 12 weeks, while maximum walking distance increased from 84.6 to 171.8 meters. In the control group, pain-free walking distance increased from 40 meters at baseline to 69.6 meters at 12 weeks, while maximum walking distance increased from 93.4 to 114.3 meters.

At 4 weeks, patients on the shockwave intervention had greater differences on the EuroQol 5-Dimension 3-Level survey (P=0.03), on the SF-36 General Health (P=0.004) and Vitality (P=0.03) domains, and on the SF-36 Physical Component Summary (PCS; P=0.02). An advantage on the PCS was seen at 8 weeks as well.

Along with the findings from the post hoc analysis and the single-center design, other limitations included the use of a constant load treadmill test to assess walking distances.

Correction: This story was updated to reflect that the sham arm had the higher rates of diabetes and coronary artery disease/ischemic heart disease at baseline.

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