Peter Schneider (San Francisco, USA) and Thomas Zeller (Bad Krozingen, Germany), alongside co-authors Jos van den Berg (Lugano, Switzerland), Yann Gouëffic (Paris, France) and Sabine Steiner (Vienna, Austria), reflect on the new European Society for Vascular Surgery (ESVS) guideline for asymptomatic peripheral arterial disease (PAD) and intermittent claudication.
Clinical practice guidelines play an important role in the management of vascular disease and the trust that vascular specialists place in guidelines is predicated on the assumption of development in a thoughtful and evidence-based manner. The recent ESVS guideline update on the management of claudication indicates that, “For patients with intermittent claudication undergoing endovascular femoropopliteal intervention, the routine adjunctive use of paclitaxel-coated balloons or paclitaxel-eluting stents is not recommended owing to the lack of demonstrated quality-of-life (QoL) benefit and concerns regarding potential long-term mortality risk”.1 The new guideline in femoropopliteal treatment is such an abrupt change of course from the previous recommendations and from worldwide practice, that further consideration is warranted.2
Claudication is a common problem that causes disability presenting with a wide range of severity. Exercise and lifestyle changes should be instituted and medical management optimised. There is broad agreement on these principles of management, and this is reflected in the current guidelines. Some patients are severely affected to the point of being considered for intervention. The recent update on claudication management is atypical of previous efforts from the standpoint of the evidence used to support the guideline and the manner in which the new guideline was derived. The new evidence for this update is based primarily upon the SWEDEPAD 2 trial.3 Usual practice in many (if not most) countries is the routine use of paclitaxel-coated devices in the endovascular management of femoropopliteal disease when treating claudication. This approach is based upon more than 20 years of worldwide clinical experience and dozens of positive studies—including randomised controlled trials (RCTs), real-world evidence, and meta-analyses—demonstrating the benefit of drug delivery in femoropopliteal revascularisation.
SWEDEPAD 2 was a valiant, sizeable and valuable effort at better understanding PAD. However, it was a single trial in a single country positioned as the primary source of information to support a major guideline change. Standard of care could be different in Sweden than in other countries and may have limited generalisability. Like all clinical trials, there were pragmatic limitations. The trial was enrolled over nine years and included only a small percentage of those being treated. There was a high percentage of 40.4% of Rutherford 1 and 2 patients treated. There was no standardisation of devices used, protocol for use, vessel preparation, or follow-up imaging. The authors present paclitaxel-coated devices as if a class effect exists but it is well recognised that not all devices are the same. Many paclitaxel-coated devices used in SWEDEPAD 2 are associated with poorer outcomes in RCTs or may lack proof of efficacy. Follow-up was performed in the style of a registry. Primary patency and clinically driven target-lesion revascularisation (CD-TLR) were not assessed and there was no imaging collected or core labs. Target-vessel revascularisation (TVR) was assessed but without imaging; it is not known if reinterventions were at the target lesion or at the inflow or outflow segments. The primary endpoint was based upon QoL assessment. As more than 40% were Rutherford class 1–2 and had less severe symptoms, it may never have been possible to demonstrate a significant improvement in QoL in these patients. Although QoL is important, it is assessed using a survey that is subjective and open to the bias of the treating team and the person administering the survey. There was no training or standardisation of how the QoL assessment was administered. Is there another major RCT in the vascular space with QoL as a primary endpoint, especially as the primary source of evidence to drive a guideline change? One might consider use of QoL as a primary endpoint to be experimental on its own.
The guideline raises concerns about a potential long-term mortality risk associated with paclitaxel-coated devices. However, pooled analyses of randomised clinical trials have produced conflicting conclusions regarding mortality after use of these devices in the lower extremities.4,5 Assessment of mortality risk in earlier trials has been complicated by factors such as crossover, loss to follow-up, and lesion-length differences, issues that do not appear to have been adequately addressed in SWEDEPAD 2. Furthermore, the credibility of a mortality signal observed only at five years, but not at one, two, three, four, six, seven, eight, or nine years, is questionable. SWEDEPAD 1, which included more patients with five-year follow-up, also showed no increase in mortality.6 Large national databases provide a more robust assessment of long-term safety. A nationwide study based on
10 years of medico-administrative data from 259,137 adults found no association between paclitaxel-coated devices and mortality.7 Finally, no plausible biological mechanism, dose-response relationship, or consistent temporal association has been demonstrated. While continued surveillance and scientific debate remain warranted, the current evidence does not support stronger conclusions.
Societal guidelines such as these produced by the ESVS typically involve a guidelines writing committee with any recommendations graded on strength (class) and level of evidence. While guidelines are often updated to include new trial data, they are typically based on all data available. For these guidelines, the committee focused their review only on RCTs published between November 2022 and November 2025 with the major focus being on SWEDEPAD 2. This ignores high-quality RCTs that have consistently shown that paclitaxel-coated devices are associated with superior patency and lower reintervention rates compared to non-coated technologies when treating claudicants with femoropopliteal disease. Using the ESVS grading system, these findings would be graded as Class 1 (evidence that the treatment is beneficial and effective) or at least Class IIa (weight of evidence favours usefulness). The level of evidence is clearly Level A (data derived from multiple RCTs or meta-analyses of RCTs). Quality of the data must inform guideline recommendations rather than be ignored.
In order for guidelines to continue to play a prominent role in the management of vascular disease, the process should be transparent, and the result should make some practical sense based upon all available data. In the recent and abrupt ESVS guideline change on claudication, much important and high-quality information is ignored, while a single study with somewhat limited applicability has assumed an outsized role to support the update.
References:
- Nordanstig J, et al. Editor’s choice – Focused update on paclitaxel coated technologies, from the 2024 European Society for Vascular Surgery (ESVS) guidelines on the management of asymptomatic peripheral arterial disease and intermittent claudication. Eur J Vasc Endovasc Surg. 2026 Jun;71(6):923–927.
2. Nordanstig J, et al. Editor’s choice – European Society for Vascular Surgery (ESVS) 2024 clinical practice guidelines on the management of asymptomatic lower limb peripheral arterial disease and intermittent claudication. Eur J Vasc Endovasc Surg. 2024 Jan;67(1):9-96.
3. Nordanstig J, et al. 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 Sep 13;406(10508):1115–1127.
4. Parikh SA, et al. Mortality in randomised controlled trials using paclitaxel-coated devices for femoropopliteal interventional procedures: an updated patient-level meta-analysis. Lancet. 2023 Nov 18;402(10415):1848–1856.
5. Katsanos K, et al. Editor’s choice – Dynamic risk of death following application of paclitaxel-coated devices in the femoropopliteal artery: a contemporary meta-analysis of randomised controlled trials. Eur J Vasc Endovasc Surg. 2026 Jun;71(6):928–941.
6. Falkenberg M, et al. Paclitaxel-coated versus uncoated devices for infrainguinal endovascular revascularisation in chronic limb-threatening ischaemia (SWEDEPAD 1): a multicentre, participant-masked, registry-based, randomised controlled trial. Lancet. 2025 Sep 13;406(10508):1103–1114.
7. Wargny M, et al. Mortality in a nationwide practice-based cohort receiving paclitaxel-coated devices for lower limb peripheral artery disease. JACC. 2024 Mar;83(13):1207–1221.
Peter Schneider is a professor of vascular surgery at the University of California, San Francisco (San Francisco, USA); Thomas Zeller is head of the Angiology Department at University Heart-Center Freiburg (Bad Krozingen, Germany); Jos van den Berg is an interventional radiologist at Clinica Luganese Moncucco (Lugano, Switzerland); Yann Gouëffic is a professor of vascular surgery at Hôpital Paris St Joseph (Paris, France); and Sabine Steiner is head of angiology at the Medical University of Vienna (Vienna, Austria).
The authors have declared the following disclosures:
Peter Schneider: consultant to Medtronic, Boston Scientific, Cagent, Abbott, Endologix, Shockwave, Stryker, Healthcare Inroads, Cordis, Protexa
Thomas Zeller: honoraria received from: Acotec, BD Bard, Biotronik, Boston Scientific, Cook Medical, Cordis, Medtronic, Veryan; consulted for: Boston Scientific, Gore, Medtronic, Shockwave, VentureMed, Veryan, Reflow Medical; institutional grants for research, clinical trial, or drug studies received from: Acotec, Ablative Solutions, BD Bard Peripheral Vascular, Boston Scientific, Contego Medical, Cook Medical, Cordis, CSI, Gore, iVascular, MedAlliance, Medtronic, Micro Medical, R3 Vascular, Recor Medical, Reflow Medical, Reva Medical, Shockwave, Surmodics, Terumo, TriReme, University of Jena; stock options: ANT
Jos van den Berg: no relevant disclosures
Yann Gouëffic: research funding from General Electric, Gore, Bentley, Boston Scientific, Penumbra
