Paclitaxel-Coated Devices for PAD Evaluated in SWEDEPAD 1 and 2 Trials

September 3, 2025—The European Society of Cardiology (ESC) announced the presentation of new findings from the SWEDEPAD 1 and 2 trials of chronic limb-threatening ischemia (CLTI) and intermittent claudication, respectively, demonstrating that paclitaxel-coated devices were not associated with reduced risk of amputation or improved quality of life compared with uncoated devices.

ESC reported in its press release that clinicians should carefully consider the use of drug-coated stents over uncoated devices, and that devices coated with antiproliferative agents other than paclitaxel warrant further investigation.

The findings from the SWEDEPAD 1 and 2 pragmatic, participant-blinded, registry-based randomized trials conducted at 22 sites in Sweden were presented in a Hot Line session at the ESC Congress 2025. Simultaneously, the SWEDEPAD 1 and SWEDEPAD 2 findings were both published in The Lancet.

In the ESC press release, the rationale for the trials was explained by Principal Co-Investigator Professor Joakim Nordanstig, MD.

“Drug-coated balloons and stents have been shown to reduce restenosis and the need for reinterventions in the endovascular treatment of peripheral artery disease (PAD),” stated Prof. Nordanstig. “However, there are uncertainties regarding whether drug-coated devices improve outcomes that are meaningful to patients, quality of life and reducing amputations, and there are some concerns over safety. We investigated these and other endpoints in two trials in PAD—one in CLTI and one in intermittent claudication—comparing drug-coated and uncoated devices.”

The ESC press release outlined the specific findings of the two trials.

SWEDEPAD 1 was composed of 2,355 patients with CLTI (Rutherford stage 4-6) undergoing infrainguinal endovascular treatment who were randomized 1:1 to drug-coated (paclitaxel, > 99%) or uncoated balloons or stents. The investigators found:

• There was no significant difference in the primary endpoint of time to ipsilateral above-ankle amputation with drug-coated versus uncoated devices (hazard ratio [HR], 1.05; 95% CI, 0.87-1.27) during 5 years of follow-up.
• Target vessel reinterventions were reduced in the drug-coated group during the first year (HR, 0.81; 95% CI, 0.66-0.98), but this difference disappeared with longer follow-up.
• There was no difference in all-cause mortality or in quality of life as assessed using the VascuQoL-6 questionnaire.

SWEDEPAD 2 was composed of 1,155 patients with intermittent claudication (Rutherford stage 1-3) undergoing infrainguinal endovascular treatment, randomized 1:1 after successful guidewire crossing to receive either drug-coated (paclitaxel, 100%) or uncoated balloons or stents. The investigators found:

• There was no difference in the primary efficacy endpoint of quality of life between the drug-coated and uncoated groups at 12 months (mean difference in VascuQoL-6 scores: –0.02; 95% CI, –0.66 to 0.62).
• Target vessel reintervention rates were not different at 1 year during a median follow-up of 6.2 years.
• All-cause mortality did not differ over 7.1 years (HR 1.18; 95% CI, 0.94-1.48), although higher 5-year mortality was noted with drug-coated versus uncoated devices (HR 1.47; 95% CI, 1.09-1.98).

The findings were further summarized in the ESC press release by Principal Co-Investigator Professor Mårten Falkenberg, PhD, who stated, “Paclitaxel-coated devices were not effective in preventing amputation in CLTI or improving quality of life in intermittent claudication. Given the signal of increased mortality with intermittent claudication, clinicians should carefully evaluate the potential risks and benefits when considering these expensive devices. Devices incorporating antiproliferative agents other than paclitaxel warrant further investigation in PAD.”