==== Front Cardiovasc Intervent Radiol Cardiovasc Intervent Radiol Cardiovascular and Interventional Radiology 0174-1551 1432-086X Springer US New York 32968830 2620 10.1007/s00270-020-02620-4 Commentary 24-Month Registry Results on Drug-Coated Balloon Angioplasty Below the Knee: Strong Enough Evidence to Convince the Sceptics? http://orcid.org/0000-0002-4048-3938Teichgräber Ulf ulf.teichgraeber@med.uni-jena.de grid.275559.90000 0000 8517 6224Department of Radiology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany 23 9 2020 23 9 2020 2021 44 1 19 20 14 7 2020 4 8 2020 © The Author(s) 2020Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.issue-copyright-statement© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2021 ==== Body Critical limb ischemia (CLI) requires immediate revascularization to prevent limb loss. In less-complex disease and in patients with severe comorbidities, the endovascular approach can be the preferred strategy. However, so far, research on Paclitaxel drug-coated balloon (DCB) angioplasty of below-the-knee (BTK) arteries gives rise to controversy. Initially, the single-center DEBATE-BTK study (65 DCB vs. 67 POBA participants) suggested a potential advantage of DCB angioplasty over standard balloon angioplasty (plain old balloon angioplasty; POBA) [1]. DCB significantly reduced the incidence of 12-month binary restenosis and target lesion revascularization (TLR). No major amputation was needed. In contrast, the larger, multi-center IN.PACT DEEP trial that evaluated the same DCB (IN.PACT Amphirion) failed to meet superiority of DCB over POBA and showed only comparable 5-year effectiveness (follow-up completed in 95 DCB and 49 POBA participants). The tendency to an increased rate of major amputations with DCB angioplasty at 12 months weakened throughout 5-years (15.4% DCB vs. 10.6% POBA; p = 0.11) [2]. The randomized BIOLUX P-II trial (36 DCB vs. 36 POBA participants) presented 12-month results on the Passeo-18 BIOLUX DCB and also confirmed only comparable effectiveness between DCB and POBA without any safety signal from DCB (major amputation: DCB 3.3% vs. POBA 5.6%; p = 0.63) [3]. Finally, 12-month outcomes from the APOLLO observational study on the ELUTAX SV DCB in CLI patients (164 participants) revealed estimates of primary patency and freedom from TLR of 68.5% and 90.6%, respectively. Incidence of major amputation and mortality was 5% and 15.9%, respectively [4]. In this issue of CVIR, Tepe et al. present 24-month results of DCB angioplasty in a pre-specified subgroup of 151 participants with BTK lesions from the real-world BIOLOUX P-III registry [5]. Most of the participants had CLI (76.0%) with a share of 22.3% categorized as Rutherford-Becker class 6. A total of 62.9% participants were diabetics. Mean lesion length was 7.9 cm, proportionate share of total occlusions 18.4%, and that of severely calcified lesions 9.8%. Lesion preparation was conducted in 73.0% and bailout stenting in 1.1% of lesions. No data are provided whether inflow vessels were diseased or treated. At 24 months, primary patency and freedom from TLR were favorable (82.8% and 90.9%, respectively), however, against the background of 9.9% major amputations and 20.8% mortality. Overall, Tepe et al. provided valuable data on effectiveness of DCB, however, no direct comparison with POBA, the standard of care, which would be needed to prove efficacy. The range of 12-month effectiveness across DCB studies for BTK lesions is large (primary patency 49.2–86.6%; freedom from TLR 68.7–90.6% [3, 5]). This also applies to safety (major amputation 0.0–9.0%; mortality 8.8–15.9% [1, 2, 4]). With regard to safety, neither the recent study of Tepe et al. nor any of the earlier studies were powered to compare major amputation or all-cause mortality rates that should be seen even in light of possible paclitaxel embolization and its potential adverse side effects. Whether differences are due to patient risk, limb threat according to wound grading, anatomic complexity, lesion preparation, or to index procedure and DCB type can only be imagined. However, except for mortality, the recent 24-month results suggest a relatively stable course of the disease throughout the second year after index procedure. After all, 5-year mortality in the IN.PACT DEEP trial was similar across groups (DCB 39.4% vs. POBA 44.9%) and mortality might comply with the advanced stage of the disease. In summary, both efficacy and safety of DCB in BTK lesions are still to be evaluated with appropriately controlled, adequately powered trials and long-term follow-ups. Until then, POBA should remain standard of care when infra-popliteal endovascular revascularization is indicated. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Funding Open Access funding provided by Projekt DEAL. Compliance with Ethical Standards Conflict of interest Educational grant by Aachen Resonance for APOLLO trial. Consent for Publication Not applicable. Ethical Approval Not applicable. Informed Consent Not applicable. ==== Refs References 1. Liistro F Porto I Angioli P Drug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in diabetic patients with critical limb ischemia Circulation 2013 128 6 615 621 10.1161/CIRCULATIONAHA.113.001811 23797811 2. Zeller T Micari A Scheinert D The IN.PACT DEEP clinical drug-coated balloon trial: 5-year outcomes JACC Cardiovasc Interv 2020 13 4 431 443 10.1016/j.jcin.2019.10.059 32081236 3. Zeller T Beschorner U Pilger E Paclitaxel-Coated Balloon in Infrapopliteal Arteries: 12-Month Results From the BIOLUX P-II Randomized Trial (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries) JACC Cardiovasc Interv 2015 8 12 1614 1622 10.1016/j.jcin.2015.07.011 26493253 4. Teichgräber U Lehmann T Thieme M Drug-coated balloon angioplasty of infrapopliteal lesions in patients with critical limb ischaemia: 1-year results of the APOLLO trial Cardiovasc. Intervent. Radiol. 2019 42 10 1380 1390 10.1007/s00270-019-02279-6 31286197 5. Tepe G Wang J Corpataux J-M BIOLOUX P-III Passeo-18 Lux all-comers registry: 24-month results in below-the-knee arteries Cardiovasc. 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