Two large randomized trials presented at ESC Congress 2025 have challenged the clinical value of drug-coated devices in peripheral artery disease, showing that paclitaxel-coated stents and balloons failed to improve patient-centered outcomes compared to uncoated alternatives.
The SWEDEPAD 1 and 2 trials, conducted across 22 sites in Sweden, examined whether drug-coated devices could deliver meaningful benefits beyond the established reduction in restenosis rates. The results, simultaneously published in The Lancet, revealed no significant improvements in amputation prevention or quality of life measures.
Chronic Limb-Threatening Ischemia Results
SWEDEPAD 1 enrolled 2,355 patients with chronic limb-threatening ischemia (Rutherford stage 4-6) undergoing infra-inguinal endovascular treatment. Patients were randomized 1:1 to receive either drug-coated or uncoated balloons or stents, with over 99% of drug-coated devices delivering paclitaxel.
The trial found no significant difference in the primary endpoint of time to ipsilateral above-ankle amputation between drug-coated and uncoated devices over 5 years of follow-up (hazard ratio 1.05; 95% confidence interval 0.87 to 1.27). While target vessel reinterventions were initially reduced in the drug-coated group during the first year (HR 0.81; 95% CI 0.66 to 0.98), this benefit disappeared with longer follow-up.
"Paclitaxel-coated devices were not effective in preventing amputation in chronic limb-threatening ischaemia," said Principal Co-Investigator Professor Mårten Falkenberg from Sahlgrenska University Hospital and the University of Gothenburg, Sweden.
Intermittent Claudication Findings
SWEDEPAD 2 randomized 1,155 patients with intermittent claudication (Rutherford stage 1-3) to drug-coated or uncoated devices after successful guidewire crossing. All drug-coated devices delivered paclitaxel.
The study showed no difference in the primary efficacy endpoint of quality of life between groups at 12 months, with a mean difference in VascuQoL-6 scores of -0.02 (95% CI -0.66 to 0.62). Target vessel reintervention rates remained similar at 1 year and over a median follow-up of 6.2 years.
Concerning safety signals emerged in this population, with higher 5-year mortality observed with drug-coated versus uncoated devices (HR 1.47; 95% CI 1.09 to 1.98), though all-cause mortality over 7.1 years did not differ significantly (HR 1.18; 95% CI 0.94 to 1.48).
Clinical Implications
The trials addressed critical uncertainties about drug-coated devices in PAD treatment. "Drug-coated balloons and stents have been shown to reduce restenosis and the need for reinterventions in the endovascular treatment of PAD. 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," explained Principal Co-Investigator Professor Joakim Nordanstig from the University of Gothenburg, Sweden.
The findings have immediate implications for clinical practice, particularly given the higher costs associated with drug-coated devices. "Given the signal of increased mortality with intermittent claudication, clinicians should carefully evaluate the potential risks and benefits when considering these expensive devices," Professor Falkenberg noted.
Future Research Directions
The researchers emphasized that their findings specifically relate to paclitaxel-coated devices and should not be extrapolated to all drug-coated technologies. "Devices incorporating antiproliferative agents other than paclitaxel warrant further investigation in PAD," Professor Falkenberg concluded.
The pragmatic, participant-blinded, registry-based design of both trials strengthens the real-world applicability of these findings, providing robust evidence to guide clinical decision-making in PAD management.
