Swedish Drug Elution Trial in Peripheral Arterial Disease - SWEDEPAD

Aug 31, 2025
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Fred M. Kusumoto, MD, FACC; Deepak L. Bhatt, MD, MPH, MBA, FACC
Date Updated:
08/31/2025
Original Posted Date:
12/21/2020
References

Highlighted text has been updated as of Aug. 31, 2025.

Contribution To Literature:

The SWEDEPAD trial did not find an association between paclitaxel-eluting stents/balloons and increased mortality. Likewise, no difference in all-cause mortality was found in SWEDEPAD 1; however, in SWEDEPAD 2, all-cause mortality was not different over the total follow-up period but was significantly higher in the paclitaxel-coated group over 5 years.

Description:

Meta-analyses have raised concern that paclitaxel-eluting stents/balloons are associated with increased mortality when used for the treatment of symptomatic peripheral arterial disease. The goal of the present trial was to evaluate drug-coated devices compared with uncoated devices for treatment of symptomatic peripheral arterial disease.

Study Design

  • Randomized
  • Parallel
  • Stratified
  • Open-label

Patients with symptomatic peripheral arterial disease undergoing endovascular lower extremity revascularization were randomized to a coated device (n = 1,149) versus an uncoated device (n = 1,140).

  • Total number of enrollees: 2,289
  • Duration of follow-up: 2.5 years
  • Mean patient age: 75 years
  • Percentage female: 45%
  • Percentage with diabetes: 46%

Inclusion criteria:

  • Intermittent claudication or chronic limb-threatening ischemia
  • Infrainguinal peripheral arterial disease
  • Eligible for endovascular revascularization

Exclusion criteria:

  • Acute lower limb ischemia
  • Infrainguinal aneurysmal disease
  • Participation in another peripheral arterial disease trial

Principal Findings:

The primary outcome, all-cause mortality during the entire follow-up period, occurred in 25.5% of the drug-coated device group compared with 24.6% of the uncoated device group (p = not significant). Results were the same among those with chronic limb-threatening ischemia and those with intermittent ischemia.

Secondary outcomes:

All-cause mortality at 1 year occurred in 10.2% of the drug-coated device group compared with 9.9% of the uncoated device group (p = not significant). Results were the same among those with chronic limb-threatening ischemia and those with intermittent ischemia.

SWEDEPAD 1 trial: 2,400 patients (median age, 77 years; 44% women) with Rutherford stage 4-6 critical limb-threatening ischemia undergoing infrainguinal endovascular revascularization were randomly assigned to treatment with paclitaxel-coated (n=1,206) or uncoated (n=1,194) devices; 75% had wounds or tissue loss (Rutherford stage 5 or 6).

After a median 2.67-year follow-up, no significant difference was found in the rate of ipsilateral major amputation comparing paclitaxel-coated with uncoated devices (hazard ratio [HR] 1.05, 95% CI 0.87-1.27; p=0.61). There was no difference in all-cause mortality or amputation-free survival between groups.

SWEDEPAD 2 trial: 1,155 patients (median age, 73 years; 46% women) with intermittent claudication (Rutherford stage 1-3 peripheral arterial disease) undergoing infrainguinal endovascular revascularization were randomly assigned to paclitaxel-coated (n=577) or uncoated (n=578) devices; 60% had Rutherford stage 3 claudication.

At 12 months, no significant differences in Vascular Quality of Life Questionnaire (VascuQoL-6) scores were found between the paclitaxel-coated and uncoated groups (mean difference –0.02, 95% CI –0.66 to 0.62; p=0.96). All-cause mortality did not differ over a median 7.1 years (HR 1.18; p=0.16); however, 5-year mortality was higher in the paclitaxel-coated device group (4.57 vs. 3.28 per 100 person-years; HR 1.47; p=0.010).

Interpretation:

Among patients with symptomatic peripheral arterial disease, drug-coated devices for treatment of symptomatic peripheral arterial disease were not associated with increased mortality in the SWEDEPAD or SWEDEPAD 1 trials. In these trials, there was not a clear mechanism for the previously documented harmful association. The SWEDEPAD 2 trial, however, did show a significantly higher incidence of all-cause mortality in the paclitaxel-coated group up to 5 years, although not over the total follow-up period.

Given the combined results of SWEDEPAD 1 and 2, which show no reduction in amputation for chronic limb-threatening ischemia, no improvement in quality of life for intermittent claudication, and possible late mortality risks, the authors write that paclitaxel-coated devices should be used cautiously for the management of peripheral arterial disease.

References:

Falkenberg M, James S, Andersson M, et al., on behalf of the SWEDEPAD trial investigators. Paclitaxel-coated versus uncoated devices for infrainguinal endovascular revascularization in chronic limb-threatening ischemia (SWEDEPAD 1): a multicentre, participant-masked, registry-based, randomized controlled trial. Lancet 2025;Aug 31:[Epub ahead of print].

Nordanstig J, James S, Andersson M, et al., on behalf of the SWEDEPAD trial investigators. Paclitaxel-coated versus uncoated devices for infrainguinal endovascular revascularisation in patients with intermittent claudication (SWEDEPAD 2): a multicentre, participant-masked, registry-based, randomised controlled trial. Lancet 2025;Aug 31:[Epub ahead of print].

Editorial Comment: Katsanosa K, Spiliopoulos S. Paclitaxel in the lower limbs: harm outweighs the benefit. Lancet 2025;Aug 31:[Epub ahead of print].

Presented by Dr. Marten Falkenberg at the European Society of Cardiology Congress, Madrid, Spain, Aug. 31, 2025.

Nordanstig J, James S, Andersson M, et al. Mortality With Paclitaxel-Coated Devices in Peripheral Artery Disease. N Engl J Med 2020;383:2538-46.

Clinical Topics: Cardiac Surgery, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Interventions and Vascular Medicine

Keywords: Diabetes Mellitus, Drug-Eluting Stents, Endovascular Procedures, Geriatrics, Intermittent Claudication, Ischemia, Lower Extremity, Myocardial Revascularization, Paclitaxel, Peripheral Arterial Disease, Stents, Vascular Diseases, ESC25, ESC Congress


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