Angioplastie mit Sirolimus-beschichtetem Ballon: der neue Standard in der Behandlung der PAVK?

Zusammenfassung

Die endovaskuläre Revaskularisierung mit Paclitaxel-beschichteten Ballons zur Behandlung der peripheren arteriellen Verschlusskrankheit hat sich im femoropoplitealen Segment als wirksame Therapieoption erwiesen. Der antiproliferative Effekt von Paclitaxel verhindert Restenosen. Im infrapoplitealen Segment dagegen ist die Evidenz derzeit noch widersprüchlich. Allerdings gibt es Hinweise auf ein erhöhtes Amputations- und Mortalitätsrisiko ab 2 Jahren nach Angioplastie mit Paclitaxel-beschichteten Ballons. Dies könnte auf einen dosisabhängigen zytotoxischen Effekt von Paclitaxel zurückzuführen sein. Sirolimus-beschichtete Ballons könnten daher eine Alternative sein, weil Sirolimus nicht zytotoxisch, sondern zytostatisch wirkt und damit ein weites therapeutisches Fenster aufweist.

Drei einarmige Pilotstudien (50, 25, bzw. 50 Patient*innen) zeigen, dass die Angioplastie mit Sirolimus-beschichteten Ballons zu vergleichbaren Ergebnissen führt, wie von Paclitaxel-beschichteten Ballons berichtet (Lumenverlust nach 6 Monaten: 0,29 mm; primäre Offenheit nach 12 Monaten: femoropopliteal 79%–82%, infrapopliteal 59%; Freiheit von Revaskularisierung der Zielläsion nach 12 Monaten: femoropopliteal 83%–94%, infrapopliteal 86%). Randomisierte kontrollierte Studien zum Vergleich mit Standard-Ballon Angioplastie und mit Paclitaxel-beschichteten Ballons für die Behandlung von Claudicatio intermittens oder chronischer Gliedmaßen-gefährdender Ischämie sind aktiv und werden voraussichtlich ab Mitte 2024 erste Ergebnisse zu Wirksamkeit und Sicherheit liefern.

Diese Übersichtsarbeit stellt die Ergebnisse der Pilotstudien zur Angioplastie mit Sirolimus-beschichteten Ballons zur Behandlung der peripheren arteriellen Verschlusskrankheit vor und gibt einen Überblich über aktuell laufende randomisierte kontrollierte Studien.

Abstract

Endovascular revascularisation with paclitaxel-coated balloons for the treatment of peripheral artery disease has been shown to be an effective therapeutic option in the femoropopliteal segment. The antiproliferative effect of paclitaxel prevents restenosis. In contrast, in the infra-popliteal segment, the evidence is currently conflicting. However, there is evidence of an increased risk of amputation and mortality from the second year after angioplasty with paclitaxel-coated balloons. This may be due to a dose-dependent cytotoxic effect of paclitaxel. Sirolimus-coated balloons might therefore be an alternative because sirolimus is cytostatic rather than cytotoxic and thus has a wide therapeutic window.

Three single-arm pilot studies (50, 25, and 50 patients, respectively) show that angioplasty with sirolimus-coated balloons leads to comparable results to those reported from paclitaxel-coated balloons (late lumen loss at 6 months: 0.29 mm; primary patency at 12 months: femoropopliteal 79%–82%, infra-popliteal 59%; freedom from target lesion revascularization at 12 months: femoropopliteal 83%–94%, infra-popliteal 86%). Randomised controlled trials comparing standard balloon angioplasty and paclitaxel-coated balloons for the treatment of intermittent claudication or chronic limb-threatening ischaemia are active and are expected to provide efficacy and safety results from mid 2024.

This review presents the results of pilot studies on angioplasty with sirolimus-coated balloons for the treatment of peripheral artery disease and reviews currently ongoing randomised controlled trials.

Schlüsselwörter

medikamentenbeschichtete Ballons - periphere arterielle Verschlusserkrankung - Angioplastie - Sirolimus

Keywords

drug-coated balloon - peripheral arterial occlusion disease - angioplasty - sirolimus

Publication History

Received: 06 July 2023

Accepted: 09 September 2023

Article published online:
16 October 2023

• Literatur

• 1 Fowkes FG, Rudan D, Rudan I. et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013; 382: 1329-1340 DOI: 10.1016/s0140-6736(13)61249-0. (PMID: 23915883)
• 2 Aboyans V, Ricco JB, Bartelink MEL. et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Endorsed by: the European Stroke Organization (ESO), The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J 2018; 39: 763-816 DOI: 10.1093/eurheartj/ehx095. (PMID: 28886620)
• 3 Klumb C, Lehmann T, Aschenbach R. et al. Benefit and risk from paclitaxel-coated balloon angioplasty for the treatment of femoropopliteal artery disease: A systematic review and meta-analysis of randomised controlled trials. EClinicalMedicine 2019; 16: 42-50 DOI: 10.1016/j.eclinm.2019.09.004. (PMID: 31832619)
• 4 Teichgräber UK, Klumb C. Drug-coated Balloon Angioplasty in Femoropopliteal Arteries – Is There a Class Effect?. Zentralbl Chir 2017; 142: 470-480 DOI: 10.1055/s-0043-119895. (PMID: 29078242)
• 5 Giannopoulos S, Ghanian S, Parikh SA. et al. Safety and Efficacy of Drug-Coated Balloon Angioplasty for the Treatment of Chronic Limb-Threatening Ischemia: A Systematic Review and Meta-Analysis. J Endovasc Ther 2020; 27: 647-657 DOI: 10.1177/1526602820931559. (PMID: 32508220)
• 6 Jia X, Zhuang B, Wang F. et al. Drug-Coated Balloon Angioplasty Compared With Uncoated Balloons in the Treatment of Infrapopliteal Artery Lesions (AcoArt II-BTK). J Endovasc Ther 2021; 28: 215-221 DOI: 10.1177/1526602820969681. (PMID: 33118432)
• 7 Liistro F, Angioli P, Ventoruzzo G. et al. Randomized Controlled Trial of Acotec Drug-Eluting Balloon Versus Plain Balloon for Below-the-Knee Angioplasty. JACC Cardiovasc Interv 2020; 13: 2277-2286 DOI: 10.1016/j.jcin.2020.06.045. (PMID: 32950416)
• 8 Liistro F, Weinberg I, Almonacid Popma A. et al. Paclitaxel-coated balloons versus percutaneous transluminal angioplasty for infrapopliteal chronic total occlusions: the IN.PACT BTK randomised trial. EuroIntervention 2022; 17: e1445-e1454 DOI: 10.4244/EIJ-D-21-00444. (PMID: 34602386)
• 9 Katsanos K, Spiliopoulos S, Kitrou P. et al. Risk of Death Following Application of Paclitaxel-Coated Balloons and Stents in the Femoropopliteal Artery of the Leg: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc 2018; 7: e011245 DOI: 10.1161/JAHA.118.011245. (PMID: 30561254)
• 10 Katsanos K, Spiliopoulos S, Kitrou P. et al. Risk of Death and Amputation with Use of Paclitaxel-Coated Balloons in the Infrapopliteal Arteries for Treatment of Critical Limb Ischemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Vasc Interv Radiol 2020; 31: 202-212 DOI: 10.1016/j.jvir.2019.11.015. (PMID: 31954604)
• 11 Albrecht T, Schnorr B, Kutschera M. et al. Two-Year Mortality After Angioplasty of the Femoro-Popliteal Artery with Uncoated Balloons and Paclitaxel-Coated Balloons-A Pooled Analysis of Four Randomized Controlled Multicenter Trials. Cardiovasc Intervent Radiol 2019; 42: 949-955 DOI: 10.1007/s00270-019-02194-w. (PMID: 30843092)
• 12 Freisinger E, Koeppe J, Gerss J. et al. Mortality after use of paclitaxel-based devices in peripheral arteries: a real-world safety analysis. Eur Heart J 2020; 41: 3732-3739 DOI: 10.1093/eurheartj/ehz698. (PMID: 31593987)
• 13 Chen Y, Zeng Y, Zhu X. et al. Significant difference between sirolimus and paclitaxel nanoparticles in anti-proliferation effect in normoxia and hypoxia: The basis of better selection of atherosclerosis treatment. Bioact Mater 2020; 6: 880-889 DOI: 10.1016/j.bioactmat.2020.09.005. (PMID: 33024904)
• 14 Ferreira LT, Figueiredo AC, Orr B. et al. Dissecting the role of the tubulin code in mitosis. Methods Cell Biol 2018; 144: 33-74 DOI: 10.1016/bs.mcb.2018.03.040. (PMID: 29804676)
• 15 Herdeg C, Oberhoff M, Baumbach A. et al. Local paclitaxel delivery for the prevention of restenosis: biological effects and efficacy in vivo. J Am Coll Cardiol 2000; 35: 1969-1976 DOI: 10.1016/s0735-1097(00)00614-8. (PMID: 10841250)
• 16 Wessely R, Blaich B, Belaiba RS. et al. Comparative characterization of cellular and molecular anti-restenotic profiles of paclitaxel and sirolimus. Implications for local drug delivery. Thromb Haemost 2007; 97: 1003-1012 (PMID: 17549304)
• 17 Choke E, Tang TY, Peh E. et al. MagicTouch PTA Sirolimus Coated Balloon for Femoropopliteal and Below the Knee Disease: Results From XTOSI Pilot Study Up To 12 Months. J Endovasc Ther 2022; 29: 780-789 DOI: 10.1177/15266028211064816. (PMID: 34911383)
• 18 Tang TY, Yap C, Soon SXY. et al. World’s First Experience Treating TASC II C and D Tibial Occlusive Disease Using the Selution SLR Sirolimus-Eluting Balloon: Six-Month Results From the PRESTIGE Study. J Endovasc Ther 2021; 28: 555-566 DOI: 10.1177/15266028211007457. (PMID: 33843364)
• 19 Tang TY, Yap CJQ, Soon SXY. et al. 12-Months Results From the PRESTIGE Study Using Sirolimus Drug-Eluting Balloons in the Treatment of Complex BTK Tibial Atherosclerotic Lesions in CLTI Patients. Cardiovasc Revasc Med 2022; 43: 143-146 DOI: 10.1016/j.carrev.2022.03.035. (PMID: 35414445)
• 20 Zeller T, Brechtel K, Meyer DR. et al. Six-Month Outcomes From the First-in-Human, Single-Arm SELUTION Sustained-Limus-Release Drug-Eluting Balloon Trial in Femoropopliteal Lesions. J Endovasc Ther 2020; 27: 683-690 DOI: 10.1177/1526602820941811. (PMID: 32666871)
• 21 Caradu C, Lakhlifi E, Colacchio EC. et al. Systematic review and updated meta-analysis of the use of drug-coated balloon angioplasty versus plain old balloon angioplasty for femoropopliteal arterial disease. J Vasc Surg 2019; 70: 981-995.e10 DOI: 10.1016/j.jvs.2019.01.080. (PMID: 31126769)
• 22 Faenger B, Heinrich A, Hilger I. et al. Drug loss from Paclitaxel-Coated Balloons During Preparation, Insertion and Inflation for Angioplasty: A Laboratory Investigation. Cardiovasc Intervent Radiol 2022; 45: 1186-1197 DOI: 10.1007/s00270-022-03164-5. (PMID: 35689119)
• 23 Heinrich A, Engler MS, Güttler FV. et al. Systematic evaluation of particle loss during handling in the percutaneous transluminal angioplasty for eight different drug-coated balloons. Sci Rep 2020; 10: 17220 DOI: 10.1038/s41598-020-74227-1. (PMID: 33057070)
• 24 Torii S, Jinnouchi H, Sakamoto A. et al. Comparison of Biologic Effect and Particulate Embolization after Femoral Artery Treatment with Three Drug-Coated Balloons in Healthy Swine Model. J Vasc Interv Radiol 2019; 30: 103-109 DOI: 10.1016/j.jvir.2018.07.025.
• 25 Tang TY, Sulaiman MSB, Soon SXY. et al. Slow-flow phenomena following lower limb paclitaxel- and sirolimus-coated balloon angioplasty in the setting of chronic limb threatening ischaemia–a case series. Quant Imaging Med Surg 2022; 12: 2058-2065 DOI: 10.21037/qims-21-633. (PMID: 35284292)
• 26 Tepe G, Schnorr B, Albrecht T. et al. Angioplasty of femoral-popliteal arteries with drug-coated balloons: 5-year follow-up of the THUNDER trial. JACC Cardiovasc Interv 2015; 8: 102-108 DOI: 10.1016/j.jcin.2014.07.023. (PMID: 25616822)
• 27 Laird JA, Schneider PA, Jaff MR. et al. Long-Term Clinical Effectiveness of a Drug-Coated Balloon for the Treatment of Femoropopliteal Lesions. Circ Cardiovasc Interv 2019; 12: e007702 DOI: 10.1161/CIRCINTERVENTIONS.118.007702. (PMID: 31195825)
• 28 Xu Y, Liu J, Zhang J. et al. Long-term safety and efficacy of angioplasty of femoropopliteal artery disease with drug-coated balloons from the AcoArt I trial. J Vasc Surg 2021; 74: 756-762 e753 DOI: 10.1016/j.jvs.2021.01.041. (PMID: 33600928)
• 29 Teichgräber U, Lehmann T, Ingwersen M. et al. Long-Term Effectiveness and Safety of Femoropopliteal Drug-Coated Balloon Angioplasty: 5-Year Results of the Randomized Controlled EffPac Trial. Cardiovasc Intervent Radiol 2022; 45: 1774-1783 DOI: 10.1007/s00270-022-03265-1. (PMID: 36088609)
• 30 Conte MS, Bradbury AW, Kolh P. et al. Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia. Eur J Vasc Endovasc Surg 2019; 58 (Suppl. 01) S1-S109.e33 DOI: 10.1016/j.ejvs.2019.05.006. (PMID: 31182334)
• 31 Spiliopoulos S, Del Giudice C, Manzi M. et al. CIRSE Standards of Practice on Below-the-Knee Revascularisation. Cardiovasc Intervent Radiol 2021; 44: 1309-1322 DOI: 10.1007/s00270-021-02891-5. (PMID: 34173044)
• 32 Farhan S, Enzmann FK, Bjorkman P. et al. Revascularization Strategies for Patients With Femoropopliteal Peripheral Artery Disease. J Am Coll Cardiol 2023; 81: 358-370 DOI: 10.1016/j.jacc.2022.10.036. (PMID: 36697136)
• 33 Bradbury AW, Moakes CA, Popplewell M. et al. A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial. Lancet 2023; 401: 1798-1809 DOI: 10.1016/s0140-6736(23)00462-2. (PMID: 37116524)
• 34 Katsanos K, Kitrou P, Spiliopoulos S. et al. Comparative Effectiveness of Plain Balloon Angioplasty, Bare Metal Stents, Drug-Coated Balloons, and Drug-Eluting Stents for the Treatment of Infrapopliteal Artery Disease: Systematic Review and Bayesian Network Meta-analysis of Randomized Controlled Trials. J Endovasc Ther 2016; 23: 851-863 DOI: 10.1177/1526602816671740. (PMID: 27708143)