Study Title: SWEDEPAD-1 (Paclitaxel-coated versus uncoated devices for infrainguinal endovascular revascularisation in chronic limb-threatening ischaemia) & SWEDEPAD-2 (Paclitaxel-coated versus uncoated devices for infrainguinal endovascular revascularisation in patients with intermittent claudication)

Congress Presented: ESC Congress 2025, Madrid

Link: https://www.escardio.org/Congresses-Events/ESC-Congress

Prepared by: Dr. Hakan Çağlıoğlu, Dr. Mustafa Yenerçağ

Introduction:
Drug-coated devices (balloons or stents) are frequently used in coronary and peripheral interventions to reduce restenosis following revascularization; however, their effect on the risk of amputation in peripheral artery disease remains uncertain.

Objective:
In SWEDEPAD-1, the effect of paclitaxel-coated devices on above-ankle amputation rates was assessed in patients with chronic limb-threatening ischaemia undergoing infrainguinal endovascular revascularization. In SWEDEPAD-2, the clinical impact of paclitaxel-coated devices was evaluated in patients with intermittent claudication undergoing infrainguinal endovascular revascularization.

Methods
SWEDEPAD-1 and SWEDEPAD-2 were multicenter, participant-blinded, randomized controlled trials conducted at 22 centers in Sweden.
SWEDEPAD-1: Included adult patients with peripheral artery disease, Rutherford categories 4–6, planned for infrainguinal endovascular therapy. Participants were randomized 1:1 to paclitaxel-coated or uncoated devices. The primary efficacy endpoint was ipsilateral major amputation (above the ankle) during follow-up.
SWEDEPAD-2: Included adults aged ≥18 years with intermittent claudication, Rutherford categories 1–3, undergoing infrainguinal endovascular therapy, excluding those with acute thromboembolic disease or infrainguinal aneurysmal disease. Participants were randomized 1:1 to paclitaxel-coated or uncoated devices. The primary efficacy endpoint was the difference in quality of life at 1 year between groups, assessed using the Vascular Quality of Life Questionnaire-6 (VascuQoL-6), a disease-specific quality of life instrument.

Results:
SWEDEPAD-1: A total of 2400 patients were randomized to paclitaxel-coated (n=1206) or uncoated devices (n=1194). The mean age was 77 years (IQR 71–83); 1317/2355 (55.9%) were male, 1038 (44.1%) female, and 1237 (52.6%) had preoperative diabetes. The mean follow-up was 2.67 years (IQR 1.08–4.78). Most patients (1761/2351, 74.9%) presented with ulceration or tissue loss (Rutherford stage 5 or 6). Lesions were located in the femoropopliteal segment in 1241 patients (52.7%), infrapopliteal segment in 537 (22.8%), and both in 561 (23.8%). With up to 5 years of follow-up, no significant difference was observed between paclitaxel-coated and uncoated devices in ipsilateral major amputation rates (HR 1.05; 95% CI 0.87–1.27; p=0.61). There was also no difference in all-cause mortality (HR 1.04; 95% CI 0.92–1.17; p=0.54).

SWEDEPAD-2: A total of 1136 patients had adequate follow-up data: 565 randomized to paclitaxel-coated devices and 571 to uncoated devices. Mean age was 73 years (IQR 68.0–78.0); 612 (53.9%) were male and 524 (46.1%) female; 382/1135 (33.7%) had preoperative diabetes (missing data for one participant). Most patients (677/1135, 59.6%) presented with severe claudication (Rutherford category 3). Femoropopliteal interventions were performed in 1092 patients (96.1%). At 1 year, VascuQoL-6 scores did not differ between groups (mean difference –0.02; 95% CI –0.66 to 0.62; p=0.96). Over a median follow-up of 7.1 years (IQR 3.9–8.2), there was no significant difference in all-cause mortality (HR 1.18; 95% CI 0.94–1.48; p=0.16). However, 5-year mortality incidence was higher in the paclitaxel-coated device group (4.57 vs. 3.28 per 100 person-years; HR 1.47; 95% CI 1.09–1.98; p=0.010).

Conclusions:
SWEDEPAD-1: In patients with chronic limb-threatening ischaemia undergoing infrainguinal endovascular revascularization, paclitaxel-coated devices did not significantly alter major amputation rates compared with uncoated devices.

SWEDEPAD-2: In patients with intermittent claudication undergoing infrainguinal endovascular revascularization, paclitaxel-coated devices were associated with an increased mortality risk, although no significant difference was observed in overall all-cause mortality.

Commentary:
The findings of SWEDEPAD-1 indicate that device selection does not substantially affect amputation risk in the treatment of critical limb ischaemia, emphasizing the need for patient-centered individualized treatment strategies. Expectations that drug-coated devices would reduce amputation risk may not translate directly into clinical practice.

In SWEDEPAD-2, using quality of life as the primary endpoint suggests potential susceptibility to cultural and individual differences. At 1 year, no superiority of paclitaxel-coated devices over placebo or uncoated devices was observed in quality of life outcomes. These results provide new clinical support for a possible late mortality risk associated with paclitaxel.