Drug-coated stents and balloons were not associated with a reduction in amputations or improved quality of life compared with uncoated devices among patients with peripheral artery disease, according to two randomized trials.

The results of the SWEDEPAD 1 trial in patients with chronic limb-threatening ischemia and the SWEDEPAD 2 trial in those with intermittent claudication were presented at the European Society of Cardiology (ESC) Congress 2025 in Madrid, Spain, and published simultaneously in The Lancet.

The studies investigated the effectiveness of drug-coated devices, the most promising method to reduce the recurrence of stenosis after surgery, said Mårten Falkenberg, MD, a vascular surgeon at Sahlgrenska University Hospital in Gothenburg, Sweden, and co-principal investigator of the two studies.

“We wanted to know: Are drug-coated devices better for peripheral artery disease and worth the extra cost?” he said.

No Difference With Drug-Coated Devices

For SWEDEPAD 1, Falkenberg and colleagues randomly assigned 2355 patients with a median age of 77 years who had chronic limb-threatening ischemia to receive drug-coated or uncoated balloons or stents for infrainguinal endovascular treatment. In SWEDEPAD 2, they did the same with 1155 patients with a median age of 73 years who had intermittent claudication.

Any device with CE Mark approval was allowed in the trials, with more than 99% of the drug-coated devices using paclitaxel, a chemotherapy drug intended to prevent scar tissue from forming and re-narrowing the artery.

In SWEDEPAD 1, major amputations, the trial’s primary endpoint, did not differ between patients who received drug-coated devices and those who received uncoated devices (hazard ratio [HR], 1.05; 95% CI, 0.87-1.27).

Patients in the control group had more target vessel reinterventions in the first year than those in the drug-coated device group (HR, 0.81; 95% CI, 0.66-0.98), but this difference faded over longer follow-up. Mortality also did not differ between the two groups (HR, 1.01; 95% CI, 0.91-1.13).

In SWEDEPAD 2, results showed no difference in the primary endpoint of quality of life, as measured by the Vascular Quality of Life Questionnaire, at 1 year (mean difference, -0.02; P = .96). The rate of reinterventions also did not differ at 1 year or over a median follow-up of 6.2 years.

Revisiting Old Concerns

Although mortality was not significantly different between study groups over the full follow-up period of 7.1 years in SWEDEPAD 2 (HR, 1.18; 95% CI, 0.94-1.48), the researchers found that at 5 years, mortality was 47% higher among those who received drug-coated devices (HR, 1.47; 95% CI, 1.09-1.98).

This finding may be cause for concern, according to Falkenberg.

“Given the signal of increased mortality with intermittent claudication, clinicians should carefully evaluate the potential risks and benefits when considering these expensive devices,” he said.

Marianne Brodmann, MD, a cardiologist at the Medical University of Graz in Graz, Austria, and discussant for the presentation at ESC, questioned why the researchers chose to report the 5-year mortality figures in SWEDEPAD 2, given that they did not differ over the longer term. She also noted a lack of difference in mortality in the larger SWEDEPAD 1 study, even though its participants were generally older and sicker than those in SWEDEPAD 2.

Concerns about a potential increase in mortality from paclitaxel-coated devices first emerged in 2018, but subsequent studies determined they were safe, including real-world observational data from 300,000 patients in the US and Europe, she said.

The fallout from that controversy led to a rise in major amputations and deaths, according to Brodmann.

“Curiously, this [mortality] signal has only presented in smaller studies with incomplete data,” she said.

Falkenberg said the 5-year endpoint was chosen because the participants were older, so mortality was quite high over the entire follow-up period, making it difficult to tease out different effects. Randomized trials are best for studying issues like this, he added.

“We don’t think this can be addressed in large observational studies; it really has to be addressed in randomized trials such as ours,” he said.

Falkenberg and Brodmann reported having no relevant financial conflicts of interest.

Brian Owens is a freelance journalist in New Brunswick, Canada.