Background:

Peripheral artery disease (PAD) affects more than 230 million people worldwide and is responsible for intermittent claudication, tissue loss, and non-healing ulcers, with a major impact on quality of life, an aspect often underexplored in previous studies. 

Endovascular revascularisation is the treatment of choice for symptomatic PAD after optimal medical therapy. Drug-coated balloons and stents using paclitaxel have demonstrated improved outcomes in reducing vessel recoil, restenosis, and ensuring long-term patency in vascular surgery. 

However, their direct clinical benefit for patients remains insufficiently assessed, and most studies have included mixed populations of patients with intermittent claudication and critical limb ischaemia, complicating the interpretation of results.

Scientific background:

A 2018 meta-analysis by Katsanos et al. suggested an increased long-term mortality risk associated with paclitaxel-coated devices, sparking widespread concern and debate about their clinical safety and overall benefit. 

Subsequent systematic reviews of the literature from 2000 to 2014 further questioned the true clinical advantage of drug-coated over uncoated devices. To address these uncertainties, two large randomised controlled trials—SWEDEPAD 1 and SWEDEPAD 2 (Swedish Drug-Elution Trial in Peripheral Arterial Disease)—were initiated to provide more robust evidence regarding the safety and efficacy of paclitaxel-based endovascular treatments.

Objective:

The SWEDEPAD 2 trial aimed to evaluate both the efficacy and safety of paclitaxel-coated devices compared with uncoated devices in infrainguinal endovascular revascularisation. 

Beyond technical outcomes, the study focused on patient-centered endpoints, assessing symptom relief and improvement in quality of life, while specifically addressing concerns about potential long-term mortality associated with paclitaxel use.

Methods:

SWEDEPAD 2 was a large, multicentre, registry-based randomised controlled trial conducted across 22 of 28 Swedish centres using the national Swedvasc registry. Patients and statisticians were blinded, while operators were not. Randomisation (1:1) was computer-generated and stratified by centre after lesion crossing and before vessel preparation, with analysis performed on an intention-to-treat basis.

Eligible patients were ≥ 18 years old with intermittent claudication (Rutherford 1–3) due to ≥ 50 % infrainguinal stenosis or occlusion, suitable for endovascular treatment. Exclusion criteria included acute limb ischaemia, infrainguinal aneurysmal disease, previous participation in related trials, or an invalid Swedish personal ID number.

Between May 2014 and September 2023, 1,155 patients were randomised: 577 to paclitaxel-coated devices and 578 to uncoated devices. Median age was 73 years; 60 % had Rutherford class 3 disease, and 90 % were treated in the femoropopliteal segment.

The primary endpoint was quality of life at one year, assessed using the validated VascuQoL-6 questionnaire (score range 6–24). Secondary endpoints included all-cause mortality, amputation-free survival, vessel patency, target lesion and limb reintervention rates, and ABI at one and five years.

Outcomes:

At one year, the VascuQoL-6 score improved significantly in both groups — from 10 to 15 — with no difference between paclitaxel-coated and uncoated devices (median score 15 in each group; p = n.s.). The evolution curves of quality-of-life scores were superimposable, and per-protocol results were consistent with the intention-to-treat analysis.

No significant differences were observed in ankle–brachial index or vessel patency at one year, as assessed by Doppler ultrasound.