Long-Term Clinical Effectiveness of a Drug-Coated Balloon for the Treatment of Femoropopliteal Lesions

John A Laird, Peter A Schneider, Michael R Jaff, Marianne Brodmann, Thomas Zeller, D Chris Metzger, Prakash Krishnan, Dierk Scheinert, Antonio Micari, Hong Wang, Michele Masters, Gunnar Tepe, John A Laird, Peter A Schneider, Michael R Jaff, Marianne Brodmann, Thomas Zeller, D Chris Metzger, Prakash Krishnan, Dierk Scheinert, Antonio Micari, Hong Wang, Michele Masters, Gunnar Tepe

Abstract

Background While randomized trials have demonstrated the superiority of drug-coated balloon (DCB) angioplasty versus standard percutaneous transluminal angioplasty (PTA) in patients with femoropopliteal peripheral artery disease, the long-term durability of DCB angioplasty remains uncertain. Methods and Results IN.PACT SFA is a prospective, multicenter, randomized single-blinded trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA] and/or Proximal Popliteal Artery [PPA]) that enrolled 331 subjects with symptomatic (Rutherford 2-4) femoropopliteal lesions. Subjects were randomly assigned 2:1 to the IN.PACT Admiral DCB or PTA. Assessments through 5 years included freedom from clinically driven target lesion revascularization, the primary safety end point, and major adverse events. Through 5 years, patients treated with the IN.PACT Admiral DCB demonstrated a sustained treatment effect with superior freedom from clinically driven target lesion revascularization when compared with PTA (Kaplan-Meier estimate of 74.5% versus 65.3%; log-rank P=0.020). The primary safety composite was achieved in 70.7% of subjects in the DCB and 59.6% in the PTA groups ( P=0.068). The major adverse event rate was 42.9% for DCB and 48.1% for PTA ( P=0.459). There were no device- or procedure-related deaths in either group as adjudicated by an independent and blinded Clinical Events Committee. Conclusions The IN.PACT SFA randomized trial demonstrates that the IN.PACT Admiral DCB continues to perform better than PTA through 5 years with higher freedom from clinically driven target lesion revascularization. The sustained safety and effectiveness profile of this DCB supports its use as a preferred treatment choice compared with PTA for femoropopliteal lesions. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01175850 (IN.PACT SFA phase I) and NCT01566461 (IN.PACT SFA phase II).

Keywords: angioplasty; drug-coated balloons; paclitaxel; peripheral artery disease.

Figures

Figure 1.
Figure 1.
Subject flow chart in the IN.PACT SFA trial though 60 mo. Three hundred thirty-one subjects were randomized 2:1 into groups that received angioplasty with a paclitaxel drug-coated balloon (DCB) or a standard percutaneous transluminal angioplasty (PTA). Subjects were followed for 5 y. IN.PACT SFA indicates Randomized Trial of IN.PACT Admiral Paclitaxel-Coated Percutaneous Transluminal Angioplasty (PTA) Balloon Catheter vs Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA).
Figure 2.
Figure 2.
Treatment effect of a drug-coated balloon (DCB) in femoropopliteal lesions at 60 mo. Freedom from clinically driven target lesion revascularization (CD-TLR) by Kaplan-Meier estimate was significantly higher in the DCB group than in the percutaneous transluminal angioplasty (PTA) group (74.5% vs 65.3%; log-rank P=0.020) at 60 mo. Bars represent 95% CI. All target lesion revascularization events were adjudicated by the independent and blinded Clinical Events Committee.
Figure 3.
Figure 3.
Subgroup analysis of freedom from clinically driven target lesion revascularization (CD-TLR) by Kaplan-Meier estimate at 60 mo. A, Freedom from CD-TLR was significantly higher in the drug-coated balloon (DCB) group than percutaneous transluminal angioplasty (PTA; 77.1% vs 66.3%; P=0.046) in the nondiabetic subgroup. B, Freedom from CD-TLR was numerically higher in the DCB group than PTA but not statistically significant (70.3% vs 64.4%; P=0.243) in the diabetic subgroup. Bars represent 95% CI. All target lesion revascularization events were adjudicated by the independent and blinded Clinical Events Committee.
Figure 4.
Figure 4.
Post hoc analysis of freedom from clinically driven target lesion revascularization (CD-TLR) at 60 mo. Forest plot shows CD-TLR based on Kaplan-Meier estimate in key subgroups at 60 mo. Subjects with Rutherford category 4, nondiabetic, age greater than 75 y, longer lesion length (≥10 cm and ≤18 cm), total occlusion and female sex favored drug-coated ballon (DCB), while both DCB and percutaneous transluminal angioplasty (PTA) performed nonsignificantly in remaining subgroups. P value of hazard ratio between DCB and PTA was calculated using Cox Proportion Hazards model for each subgroup. Treatment-by-subgroup interactions were tested using a Cox proportional hazards model containing the main effects of treatment (IN.PACT DCB and Control PTA), subgroup and the treatment-by-subgroup interaction. ITT indicates intent-to-treat.

References

    1. Laird JR, Schneider PA, Tepe G, Brodmann M, Zeller T, Metzger C, Krishnan P, Scheinert D, Micari A, Cohen DJ, Wang H, Hasenbank MS, Jaff MR IN.PACT SFA Trial Investigators. Durability of treatment effect using a drug-coated balloon for femoropopliteal lesions: 24-month results of IN.PACT SFA. J Am Coll Cardiol. 2015;66:2329–2338. doi: 10.1016/j.jacc.2015.09.063.
    1. Tepe G, Laird J, Schneider P, Brodmann M, Krishnan P, Micari A, Metzger C, Scheinert D, Zeller T, Cohen DJ, Snead DB, Alexander B, Landini M, Jaff MR IN.PACT SFA Trial Investigators. 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;131:495–502. doi: 10.1161/CIRCULATIONAHA.114.011004.
    1. Iida O, Soga Y, Urasawa K, Saito S, Jaff MR, Wang H, Ookubo H, Yokoi H MDT-2113 SFA Japan Investigators. Drug-coated balloon vs standard percutaneous transluminal angioplasty for the treatment of atherosclerotic lesions in the superficial femoral and proximal popliteal arteries: one-year results of the MDT-2113 SFA Japan randomized trial. J Endovasc Ther. 2018;25:109–117. doi: 10.1177/1526602817745565.
    1. Schneider PA, Laird JR, Tepe G, Brodmann M, Zeller T, Scheinert D, Metzger C, Micari A, Sachar R, Jaff MR, Wang H, Hasenbank MS, Krishnan P IN.PACT SFA Trial Investigators. 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:e005891. doi: 10.1161/CIRCINTERVENTIONS.117.005891.
    1. Krishnan P, Faries P, Niazi K, Jain A, Sachar R, Bachinsky WB, Cardenas J, Werner M, Brodmann M, Mustapha JA, Mena-Hurtado C, Jaff MR, Holden AH, Lyden SP. Stellarex drug-coated balloon for treatment of femoropopliteal disease: twelve-month outcomes from the randomized ILLUMENATE pivotal and pharmacokinetic studies. Circulation. 2017;136:1102–1113. doi: 10.1161/CIRCULATIONAHA.117.028893.
    1. Rosenfield K, Jaff MR, White CJ, Rocha-Singh K, Mena-Hurtado C, Metzger DC, Brodmann M, Pilger E, Zeller T, Krishnan P, Gammon R, Müller-Hülsbeck S, Nehler MR, Benenati JF, Scheinert D LEVANT 2 Investigators. Trial of a paclitaxel-coated balloon for femoropopliteal artery disease. N Engl J Med. 2015;373:145–153. doi: 10.1056/NEJMoa1406235.
    1. Scheinert D, Micari A, Brodmann M, Tepe G, Peeters P, Jaff MR, Wang H, Schmahl R, Zeller T IN.PACT Global Study Investigators. Drug-coated balloon treatment for femoropopliteal artery disease. Circ Cardiovasc Interv. 2018;11:e005654. doi: 10.1161/CIRCINTERVENTIONS.117.005654.
    1. Brodmann M, Keirse K, Scheinert D, Spak L, Jaff MR, Schmahl R, Li P, Zeller T IN.PACT Global Study Investigators. Drug-coated balloon treatment for femoropopliteal artery disease: The IN.PACT Global Study de novo in-stent restenosis imaging cohort. JACC Cardiovasc Interv. 2017;10:2113–2123. doi: 10.1016/j.jcin.2017.06.018.
    1. Ansel GM, Brodmann M, Keirse K, Micari A, Jaff MR, Rocha-Singh K, Fernandez EJ, Wang H, Zeller T IN.PACT Global Study Investigators. Drug-coated balloon treatment of femoropopliteal lesions typically excluded from clinical trials: 12-month findings from the IN.PACT Global Study. J Endovasc Ther. 2018;25:673–682. doi: 10.1177/1526602818803119.
    1. Micari A, Brodmann M, Keirse K, Peeters P, Tepe G, Frost M, Wang H, Zeller T IN.PACT Global Study Investigators. Drug-coated balloon treatment of femoropopliteal lesions for patients with intermittent claudication and ischemic rest pain: 2-year results from the IN.PACT Global Study. JACC Cardiovasc Interv. 2018;11:945–953. doi: 10.1016/j.jcin.2018.02.019.
    1. Kansal A, Long CA, Patel MR, Jones WS. Endovascular treatment of femoro-popliteal lesions. Clin Cardiol. 2019;42:175–183. doi: 10.1002/clc.23098.
    1. Tepe G, Schnorr B, Albrecht T, Brechtel K, Claussen CD, Scheller B, Speck U, Zeller T. Angioplasty of femoral-popliteal arteries with drug-coated balloons: 5-year follow-up of the THUNDER trial. JACC Cardiovasc Interv. 2015;8(1 pt A):102–108. doi: 10.1016/j.jcin.2014.07.023.
    1. IN.PACT™ Admiral™ Instructions for Use. . Accessed January 4, 2019.
    1. Katsanos K, Spiliopoulos S, Karunanithy N, Krokidis M, Sabharwal T, Taylor P. Bayesian network meta-analysis of nitinol stents, covered stents, drug-eluting stents, and drug-coated balloons in the femoropopliteal artery. J Vasc Surg. 2014;59:1123–1133.e8. doi: 10.1016/j.jvs.2014.01.041.
    1. Jaff MR, Nelson T, Ferko N, Martinson M, Anderson LH, Hollmann S. Endovascular interventions for femoropopliteal peripheral artery disease: a network meta-analysis of current technologies. J Vasc Interv Radiol. 2017;28:1617–1627.e1. doi: 10.1016/j.jvir.2017.08.003.
    1. Dake MD, Ansel GM, Jaff MR, Ohki T, Saxon RR, Smouse HB, Machan LS, Snyder SA, O’Leary EE, Ragheb AO, Zeller T Zilver PTX Investigators. Durable clinical effectiveness with paclitaxel-eluting stents in the femoropopliteal artery: 5-year results of the Zilver PTX randomized trial. Circulation. 2016;133:1472–1483. discussion 1483. doi: 10.1161/CIRCULATIONAHA.115.016900.
    1. Shammas NW, Shammas GA, Arikat L, Shammas AN, Darrow A, Banerjee A, Rudy B. Five-year freedom from target-lesion revascularization using excimer laser ablation therapy in the treatment of in-stent restenosis of femoropopliteal arteries. J Invasive Cardiol. 2017;29:207–208.
    1. Kruse RR, Poelmann FB, Doomernik D, Burgerhof HG, Fritschy WM, Moll FL, Reijnen MM. Five-year outcome of self-expanding covered stents for superficial femoral artery occlusive disease and an analysis of factors predicting failure. J Endovasc Ther. 2015;22:855–861. doi: 10.1177/1526602815610583.
    1. Koifman E, Lipinski MJ, Buchanan K, Yu Kang W, Escarcega RO, Waksman R, Bernardo NL. Comparison of treatment strategies for femoro-popliteal disease: a network meta-analysis. Catheter Cardiovasc Interv. 2018;91:1320–1328. doi: 10.1002/ccd.27484.
    1. Feldman DN, Armstrong EJ, Aronow HD, Gigliotti OS, Jaff MR, Klein AJ, Parikh SA, Prasad A, Rosenfield K, Shishehbor MH, Swaminathan RV, White CJ. SCAI consensus guidelines for device selection in femoral-popliteal arterial interventions. Catheter Cardiovasc Interv. 2018;92:124–140. doi: 10.1002/ccd.27635.
    1. Sobieszczyk P. In-stent restenosis after femoropopliteal interventions with drug-eluting stents: same but different? JACC Cardiovasc Interv. 2016;9:835–837. doi: 10.1016/j.jcin.2016.02.015.
    1. Iida O, Takahara M, Soga Y, Hirano K, Yamauchi Y, Zen K, Kawasaki D, Nanto S, Yokoi H, Uematsu M ZEPHYR Investigators. The characteristics of in-stent restenosis after drug-eluting stent implantation in femoropopliteal lesions and 1-year prognosis after repeat endovascular therapy for these lesions. JACC Cardiovasc Interv. 2016;9:828–834. doi: 10.1016/j.jcin.2016.01.007.
    1. Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. 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.
    1. Albrecht T, Ukrow A, Werk M, Tepe G, Zeller T, Meyer DR, Kutschera M, Speck U, Waliszewski M. Impact of patient and lesion characteristics on drug-coated balloon angioplasty in the femoropopliteal artery: a pooled analysis of four randomized controlled multicenter trials. Cardiovasc Intervent Radiol. 2019;42:495–504. doi: 10.1007/s00270-018-2137-3.
    1. Schneider PA, Laird JR, Doros G, Gao Q, Ansel G, Brodmann M, Micari A, Shishehbor MH, Tepe G, Zeller T. Mortality not correlated with paclitaxel exposure: an independent patient-level meta-analysis [published online January 25, 2019]. J Am Coll Cardiol. doi: 10.1016/j.jacc.2019.01.013.
    1. Secemsky EA, Kundi H, Weinberg I, Jaff MR, Krawisz A, Parikh SA, Beckman JA, Mustapha J, Rosenfield K, Yeh RW. Association of survival with femoropopliteal artery revascularization with drug-coated devices [published online February 12, 2019]. JAMA Cardiol. doi: 10.1001/jamacardio.2019.0325.
    1. Anantha-Narayanan M, Shah SM, Jelani QU, Garcia S, Ionescu C, Regan C, Mena-Hurtado C. Drug-coated balloon versus plain old balloon angioplasty in femoropopliteal disease: an updated meta-analysis of randomized controlled trials [published online March 6, 2019]. Catheter Cardiovasc Interv. doi: 10.1002/ccd.28176.
    1. Albrecht T, Schnorr B, Kutschera M, Waliszewski MW. 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 [published online March 6, 2019]. Cardiovasc Intervent Radiol. doi: 10.1007/s00270-019-02194-w.
    1. Micari A, Nerla R, Vadalà G, Castriota F, Grattoni C, Liso A, Russo P, Pantaleo P, Roscitano G, Cremonesi A. 2-year results of paclitaxel-coated balloons for long femoropopliteal artery disease: evidence from the SFA-Long Study. JACC Cardiovasc Interv. 2017;10:728–734. doi: 10.1016/j.jcin.2017.01.028.
    1. Schmidt A, Piorkowski M, Görner H, Steiner S, Bausback Y, Scheinert S, Banning-Eichenseer U, Staab H, Branzan D, Varcoe RL, Scheinert D. Drug-coated balloons for complex femoropopliteal lesions: 2-year results of a real-world registry. JACC Cardiovasc Interv. 2016;9:715–724. doi: 10.1016/j.jcin.2015.12.267.
    1. Teymen B, Akturk S, Akturk U, Tdjani M. Comparison of drug-eluting balloon angioplasty with self-expanding interwoven nitinol stent deployment in patients with complex femoropopliteal lesions. Vascular. 2018;26:54–61. doi: 10.1177/1708538117719580.

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