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Is There a Safety Concern for Drug-Coated Balloons in Peripheral Arterial Disease?

  • New Therapies for Cardiovascular Disease (AA Bavry, Section Editor)
  • Published:
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Abstract

Purpose of Review

Drug-coated balloons (DEB) and drug-eluting stents (DES) emerged as a tool to aid in lowering the rates of neointimal hyperplasia and target lesion restenosis following endovascular peripheral arterial disease (PAD) interventions.

Recent Findings

Although the initial trials comparing these devices with non-drug balloons and stents showed favorable results, more recent data raised concerns regarding the mid to long-term safety of these devices.

Summary

In this review, we will discuss the evolution of endovascular therapy for PAD, with highlights regarding the recent debates on the long-term safety of the drug-coated devices for treatment of PAD.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209.

    Google Scholar 

  2. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg. 2007;45 Suppl S:S5–67.

    CAS  PubMed  Google Scholar 

  3. Allison MA, Ho E, Denenberg JO, Langer RD, Newman AB, Fabsitz RR, et al. Ethnic-specific prevalence of peripheral arterial disease in the United States. Am J Prev Med. 2007;32(4):328–33.

    PubMed  Google Scholar 

  4. Doshi R, Changal KH, Gupta R, Shah J, Patel K, Desai R, et al. Comparison of outcomes and cost of endovascular management versus surgical bypass for the management of lower extremities peripheral arterial disease. Am J Cardiol. 2018;122(10):1790–6.

    PubMed  Google Scholar 

  5. Hoppe H, Kaufman JA. CHAPTER 16 - Radiologic intervention in diabetic peripheral vascular disease. In: Bowker JH, Pfeifer MA, editors. Levin and O’Neal’s the diabetic foot. Seventh ed. Philadelphia: Mosby; 2008. p. 329–37.

    Google Scholar 

  6. Gray BH. Chapter 9b - Endovascular treatment of lower extremity arterial occlusive disease: femoropopliteal and tibial interventions. In: Hallett JW, Mills JL, Earnshaw JJ, Reekers JA, Rooke TW, editors. Comprehensive vascular and endovascular surgery. Second ed. Philadelphia: Mosby; 2009. p. 151–75.

    Google Scholar 

  7. Lugmayr HF, Holzer H, Kastner M, Riedelsberger H, Auterith A. Treatment of complex arteriosclerotic lesions with nitinol stents in the superficial femoral and popliteal arteries: a midterm follow-up. Radiology. 2002;222(1):37–43.

    PubMed  Google Scholar 

  8. Schillinger M, Sabeti S, Loewe C, Dick P, Amighi J, Mlekusch W, et al. Balloon angioplasty versus implantation of nitinol stents in the superficial femoral artery. N Engl J Med. 2006;354(18):1879–88.

    CAS  PubMed  Google Scholar 

  9. Sabeti S, Schillinger M, Amighi J, Sherif C, Mlekusch W, Ahmadi R, et al. Primary patency of femoropopliteal arteries treated with nitinol versus stainless steel self-expanding stents: propensity score-adjusted analysis. Radiology. 2004;232(2):516–21.

    PubMed  Google Scholar 

  10. Cejna M, Thurnher S, Illiasch H, Horvath W, Waldenberger P, Hornik K, et al. PTA versus Palmaz stent placement in femoropopliteal artery obstructions: a multicenter prospective randomized study. J Vasc Interv Radiol. 2001;12(1):23–31.

    CAS  PubMed  Google Scholar 

  11. Grimm J, Muller-Hulsbeck S, Jahnke T, Hilbert C, Brossmann J, Heller M. Randomized study to compare PTA alone versus PTA with Palmaz stent placement for femoropopliteal lesions. J Vasc Interv Radiol. 2001;12(8):935–42.

    CAS  PubMed  Google Scholar 

  12. Becquemin JP, Favre JP, Marzelle J, Nemoz C, Corsin C, Leizorovicz A. Systematic versus selective stent placement after superficial femoral artery balloon angioplasty: a multicenter prospective randomized study. J Vasc Surg. 2003;37(3):487–94.

    PubMed  Google Scholar 

  13. Vroegindeweij D, Vos LD, Tielbeek AV, Buth J, vd Bosch HC. Balloon angioplasty combined with primary stenting versus balloon angioplasty alone in femoropopliteal obstructions: a comparative randomized study. Cardiovasc Intervent Radiol. 1997;20(6):420–5.

    CAS  PubMed  Google Scholar 

  14. Laird JR, Katzen BT, Scheinert D, Lammer J, Carpenter J, Buchbinder M, et al. Nitinol stent implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-up from the RESILIENT randomized trial. J Endovasc Ther. 2012;19(1):1–9.

    PubMed  Google Scholar 

  15. Schillinger M, Sabeti S, Dick P, Amighi J, Mlekusch W, Schlager O, et al. Sustained benefit at 2 years of primary femoropopliteal stenting compared with balloon angioplasty with optional stenting. Circulation. 2007;115(21):2745–9.

    PubMed  Google Scholar 

  16. Back MR. Commentary. Sustained benefit at 2 years of primary femoropopliteal stenting compared with balloon angioplasty with optional stenting. Perspect Vasc Surg Endovasc Ther. 2008;20(2):228–30.

    PubMed  Google Scholar 

  17. Schillinger M, Sabeti S, Dick P, Amighi J, Mlekusch W, Schlager O, et al. Response to letter regarding article, “sustained benefit at 2 years of primary femoropopliteal stenting compared with balloon angioplasty with optional stenting”. Circulation. 2007;116(21):e546–e.

    Google Scholar 

  18. Kruger D. Neo-intimal hyperplasia, diabetes and endovascular injury. Cardiovasc J Afr. 2012;23(9):507–11.

    PubMed  PubMed Central  Google Scholar 

  19. Dake MD, Scheinert D, Tepe G, Tessarek J, Fanelli F, Bosiers M, et al. Nitinol stents with polymer-free paclitaxel coating for lesions in the superficial femoral and popliteal arteries above the knee: twelve-month safety and effectiveness results from the Zilver PTX single-arm clinical study. J Endovasc Ther. 2011;18(5):613–23.

    PubMed  Google Scholar 

  20. Htay T, Liu MW. Drug-eluting stent: a review and update. Vasc Health Risk Manag. 2005;1(4):263–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Werk M, Albrecht T, Meyer DR, Ahmed MN, Behne A, Dietz U, et al. Paclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the randomized PACIFIER trial. Circ Cardiovasc Interv. 2012;5(6):831–40.

    CAS  PubMed  Google Scholar 

  22. Fanelli F, Cannavale A, Corona M, Lucatelli P, Wlderk A, Salvatori FM. The “DEBELLUM”--lower limb multilevel treatment with drug eluting balloon--randomized trial: 1-year results. J Cardiovasc Surg. 2014;55(2):207–16.

    CAS  Google Scholar 

  23. Rosenfield K, Jaff MR, White CJ, Rocha-Singh K, Mena-Hurtado C, Metzger DC, et al. Trial of a paclitaxel-coated balloon for femoropopliteal artery disease. N Engl J Med. 2015;373(2):145–53.

    CAS  PubMed  Google Scholar 

  24. Scheinert D, Schulte KL, Zeller T, Lammer J, Tepe G. Paclitaxel-releasing balloon in femoropopliteal lesions using a BTHC excipient: twelve-month results from the BIOLUX P-I randomized trial. J Endovasc Ther. 2015;22(1):14–21.

    PubMed  Google Scholar 

  25. Jia X, Zhang J, Zhuang B, Fu W, Wu D, Wang F, et al. Acotec drug-coated balloon catheter: randomized, multicenter, controlled clinical study in femoropopliteal arteries: evidence from the AcoArt I trial. JACC Cardiovasc Interv. 2016;9(18):1941–9.

    PubMed  Google Scholar 

  26. Schneider PA, Laird JR, Tepe G, Brodmann M, Zeller T, Scheinert D, et al. Treatment effect of drug-coated balloons is durable to 3 years in the femoropopliteal arteries: long-term results of the IN.PACT SFA randomized trial. Circ Cardiovasc Interv. 2018;11(1):e005891.

    PubMed  PubMed Central  Google Scholar 

  27. Brodmann M, Werner M, Meyer DR, Reimer P, Kruger K, Granada JF, et al. Sustainable antirestenosis effect with a low-dose drug-coated balloon: the ILLUMENATE European randomized clinical trial 2-year results. JACC Cardiovasc Interv. 2018;11(23):2357–64.

    PubMed  Google Scholar 

  28. Lindquist J, Schramm K. Drug-eluting balloons and drug-eluting stents in the treatment of peripheral vascular disease. Semin Interv Radiol. 2018;35(5):443–52.

    Google Scholar 

  29. Bausback Y, Wittig T, Schmidt A, Zeller T, Bosiers M, Peeters P, et al. Drug-eluting stent versus drug-coated balloon revascularization in patients with femoropopliteal arterial disease. J Am Coll Cardiol. 2019;73(6):667–79.

    CAS  PubMed  Google Scholar 

  30. . Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal srtery of the leg: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2018;7(24):e011245 Findings from the meta-analysis published by Katsanos et al. suggested an increased mortality risk associated with paclitaxel-coated devices and highlighted the lack of long-term follow-up data.

    PubMed  PubMed Central  Google Scholar 

  31. Hunt BD, Popplewell MA, Davies H, Meecham L, Jarrett H, Bate G, et al. BAlloon versus stenting in severe ischaemia of the Leg-3 (BASIL-3): study protocol for a randomised controlled trial. Trials. 2017;18(1):224.

    PubMed  PubMed Central  Google Scholar 

  32. Swedish Drug-elution Trial in Peripheral Arterial Disease (SWEDEPAD) [06/01/2019]. Available from: https://clinicaltrials.gov/ct2/show/NCT02051088. Accessed 8 June 2019.

  33. (FDA) USFaDA. Treatment of peripheral arterial disease with paclitaxel-coated balloons and paclitaxel-eluting stents potentially associated with increased mortality - letter to health care providers 2019 [Available from: https://www.fda.gov/medical-devices/letters-health-care-providers/treatment-peripheral-arterial-disease-paclitaxel-coated-balloons-and-paclitaxel-eluting-stents. Accessed 8 June 2019.

  34. (FDA) USFaDA. UPDATE: Treatment of peripheral arterial disease with paclitaxel-coated balloons and paclitaxel-eluting stents potentially associated with increased mortality - letter to health care providers 2019 [Available from: https://www.fda.gov/medical-devices/letters-health-care-providers/update-treatment-peripheral-arterial-disease-paclitaxel-coated-balloons-and-paclitaxel-eluting. Accessed 8 June 2019.

  35. Granada J. Toxicological aspects and safety profile of paclitaxel [Internet]. Linc2019.cncptdlx.com. 2019 [cited 9 June 2019]. Available from: https://linc2019.cncptdlx.com/media/1116_Juan_Fernando_Granada_Solis_22_01_2019_Room_1_-_Main_Arena_1_v1.pdf [. Accessed 8 June 2019.

  36. Schneider P. DCBs over the long-term: are they safe for our PAD patients? Insights from IN.PACTTM DCB program [Internet]. Linc2019.cncptdlx.com. 2019 [cited 9 June 2019]. Available from: https://linc2019.cncptdlx.com/media/1128_Peter_Schneider_22_01_2019_Room_1_-_Main_Arena_1.pdf. Accessed 8 June 2019.

  37. Dake M. Long-term safety information on paclitaxel eluting stents: insights from the Zilver PTX programme [Internet]. Linc2019.cncptdlx.com. 2019 [cited 9 June 2019]. Available from: https://linc2019.cncptdlx.com/media/1143_Michael_Dake_22_01_2019_Room_1_-_Main_Arena_1_v2.pdf [. Accessed 8 June 2019.

  38. Drug elution in peripheral artery disease (PAD): a critical analysis from a multispecialty consortium [Internet]. 2019 [cited 9 June 2019]. Available from: https://vivaphysicians.org/vlf. Accessed 8 June 2019.

  39. SVS announces new task force on paclitaxel safety | Society for Vascular Surgery [Internet]. Vascular.org. 2019 [cited 9 June 2019]. Available from: https://vascular.org/news-advocacy/svs-announces-new-task-force-paclitaxel-safety. Accessed 8 June 2019.

  40. Physician and healthcare payer information | Medtronic [Internet]. Newsroom.medtronic.com. 2019 [cited 9 June 2019]. Available from: http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=2387744. Accessed 8 June 2019.

  41. Dake M, Ansel G, Jaff M, Ohki T, Saxon R, Smouse H et al. Correction to: Durable Clinical Effectiveness With Paclitaxel-Eluting Stents in the Femoropopliteal Artery 5-Year Results of the Zilver PTX Randomized Trial. Circulation. 2019;139(8). https://doi.org/10.1161/CIR.0000000000000657.

  42. . Schneider PA, Laird JR, Doros G, Gao Q, Ansel G, Brodmann M, et al. Correction mortality not correlated with paclitaxel exposure: an independent patient-level meta-analysis of a drug-coated balloon. Journal of the American College of Cardiology. 2019;73(20):2643 Schneider et al. performed an independent, individual patient-level meta-analysis that showed no statistically significant increase in mortality risk conflicting with prior results reported by Katsanos et al. and igniting further debate about the safety of paclitaxel-coated devices.

    Google Scholar 

  43. Dake Michael D, Ansel Gary M, Jaff Michael R, Ohki T, Saxon Richard R, Smouse HB, et al. Durable clinical effectiveness with paclitaxel-eluting stents in the femoropopliteal artery. Circulation. 2016;133(15):1472–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Kichikawa K, Ichihashi S, Yokoi H, Ohki T, Nakamura M, Komori K, et al. Zilver PTX post-market surveillance study of paclitaxel-eluting stents for treating femoropopliteal artery disease in Japan: 2-year results. Cardiovasc Intervent Radiol. 2019;42(3):358–64.

    PubMed  Google Scholar 

  45. Secemsky EA, Kundi H, Weinberg I, Jaff MR, Krawisz A, Parikh SA, et al. Association of durvival with femoropopliteal artery revascularization with drug-coated devices. JAMA Cardiol. 2019.

  46. Schneider PA, Laird JR, Doros G, Gao Q, Ansel G, Brodmann M, et al. Mortality not correlated with paclitaxel exposure. J Am Coll Cardiol. 2019;73(20):2550–63.

    PubMed  Google Scholar 

  47. Grube E, Lansky A, Hauptmann K, Di Mario C, Di Sciascio G, Colombo A et al. High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary revascularization. J Am Coll Cardiol. 2004;44(7):1368–72.

    CAS  PubMed  Google Scholar 

  48. Mauri L, Hsieh W, Massaro J, Ho K, D'Agostino R, Cutlip D. Stent Thrombosis in Randomized Clinical Trials of Drug-Eluting Stents. N Engl J Med. 2007;356(10):1020–29.

    CAS  PubMed  Google Scholar 

  49. Stettler C, Wandel S, Allemann S, Kastrati A, Morice M, Schömig A et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. The Lancet. 2007;370(9591):937–48.

    CAS  Google Scholar 

  50. Hayes D, Thor A, Dressler L, Weaver D, Edgerton S, Cowan D et al. HER2 and Response to Paclitaxel in Node-Positive Breast Cancer. N Engl J Med. 2007;357(15):1496–506.

    CAS  PubMed  Google Scholar 

  51. Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA, Hudis CA, et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008;26(8):1231–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Tepe G, Laird J, Schneider P, Brodmann M, Krishnan P, Micari A, et al. Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the IN.PACT SFA randomized trial. Circulation. 2015;131(5):495–502.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Laird John A, Schneider Peter A, Jaff Michael R, Brodmann M, Zeller T, Metzger DC, et al. Long-term clinical effectiveness of a drug-coated balloon for the treatment of femoropopliteal lesions. Circ Cardiovasc Interv. 2019;12(6):e007702.

    CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Heart and Vascular Institute, Cleveland, OH, USA

    Mohamed M. Gad & Antonette K. Karrthik

  2. School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Mohamed M. Gad

  3. Department of Internal Medicine, University of Florida, Gainesville, FL, USA

    Ahmad A. Mahmoud

  4. Division of Cardiology, University of Washington, Seattle, WA, USA

    Ahmed N. Mahmoud

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  1. Mohamed M. Gad
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  2. Antonette K. Karrthik
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  3. Ahmad A. Mahmoud
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  4. Ahmed N. Mahmoud
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Correspondence to Ahmed N. Mahmoud.

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Mohamed M. Gad, Antonette K. Karrthik, Ahmad A Mahmoud, and Ahmed N. Mahmoud declare no conflict of interest.

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Gad, M.M., Karrthik, A.K., Mahmoud, A.A. et al. Is There a Safety Concern for Drug-Coated Balloons in Peripheral Arterial Disease?. Curr Cardiol Rep 21, 126 (2019). https://doi.org/10.1007/s11886-019-1211-z

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