Critical appraisal of paclitaxel balloon angioplasty for femoral-popliteal arterial disease

Abstract

Peripheral arterial disease, particularly critical limb ischemia, is an area with urgent need for optimized therapies because, to date, vascular interventions often have limited life spans. In spite of initial encouraging technical success after femoropopliteal percutaneous transluminal angioplasty or stenting, postprocedural restenosis remains the major problem. The challenging idea behind the drug-coated balloon (DCB) concept is the biological modification of the injury response after balloon dilatation. Antiproliferative drugs administered via DCBs or drug-eluting stents are able to suppress neointimal hyperplasia, the main cause of restenosis. This article reviews the results of DCB treatments of femoropopliteal and infrapopliteal lesions in comparison to standard angioplasty with uncoated balloons. A systematic literature search was performed in 1) medical journals (ie, MEDLINE), 2) international registers for clinical studies (ie, www.clinicaltrials.gov), and 3) abstracts of scientific sessions. Several controlled randomized trials with follow-up periods of up to 5 years demonstrated the efficacy of paclitaxel -DCB technology. However, calcified lesions seem to affect the efficacy of DCB. Combinations of preconditioning methods with DCBs showed promising results. Although the mechanical abrasion of calcium via atherectomy or laser ablation showed favorable periprocedural results, the long-term impact on restenosis and clinical outcome has to be demonstrated. Major advantages of the DCBs are the rapid delivery of drug at uniform concentrations with a single dose, their efficacy in areas wherein stents have been contraindicated until now (ie, bifurcation, ostial lesions), and in leaving no stent scaffold behind. Reinterventions are easier to perform because DCBs leave no metal behind. Various combinations of DCBs with other treatment modalities may prove to be viable options in future. The follow-up results of clinical studies will evaluate the long-term impact of DCBs.

Keywords: atherectomy; critical limb ischemia; drug-coated balloon; peripheral artery disease; restenosis; stent restenosis.

Figures

Figure 1

Early clinical trials of DCB vs PTA in femoropoliteal lesions. Notes: (A) Comparison of LLL at 6 months in early clinical trials of DCB vs PTA in femoropoliteal lesions. *P≤0.05; ***P≤0.001. Error bars indicate standard deviation. (B) Comparison of TLR at 12 months in early clinical trials of DCB vs PTA in femoropoliteal lesions. *P≤0.05; **P≤0.01; ***P≤0.001. THUNDER, Local Delivery of Paclitaxel to Inhibit Restenosis during Angioplasty of the Leg Trial; FemPac, Femoral Paclitaxel Randomized Pilot Trial – Inhibition of Restenosis in Femoropopliteal Arteries: Paclitaxel-Coated vs Uncoated Balloon; PACIFIER, Paclitaxel-coated balloons In Femoral Indication to dEfeat Restenosis trial; LEVANT I, Trial Comparing the Lutonix Catheter vs Standard Balloon Angioplasty for Treatment of Femoropopliteal Arteries With and Without Stenting. Abbreviations: DCB, drug-coated balloon; LLL, late lumen loss; ns, not significant; PTA, percutaneous transluminal angioplasty; TLR, target lesion revascularization.

Figure 2

Comparison of TLR at 12 months in recent clinical trials of DCB vs PTA in femoropopliteal lesions. Notes: ***P≤0.001. IN.PACT SFA, Randomized Trial of IN.PACT Admiral™ Drug Eluting Balloon vs Standard PTA for the Treatment of Superficial Femoral and/or Popliteal Peripheral Artery Disease; LEVANT II, The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropoliteal Restenosis; ILLUMENATE FIH, Study to Evaluate Treatment of Obstructive Superficial Femoral Artery or Popliteal Lesions With A Novel Paclitaxel-Coated Percutaneous Angioplasty Balloon. Abbreviations: DCB, drug-coated balloon; ns, not significant; PTA, percutaneous transluminal angioplasty; TLR, target lesion revascularization.

Figure 3

Development of freedom from TLR over time in clinical trials of DCB vs PTA in the SFA. Notes: PACIFIER, Paclitaxel-coated balloons In Femoral Indication to dEfeat Restenosis trial; THUNDER, Local Delivery of Paclitaxel to Inhibit Restenosis during Angioplasty of the Leg Trial; LEVANT I, Trial Comparing the Lutonix Catheter vs Standard Balloon Angioplasty for Treatment of Femoropopliteal Arteries With and Without Stenting; IN.PACT SFA, Randomized Trial of IN.PACT Admiral™ Drug Eluting Balloon vs Standard PTA for the Treatment of Superficial Femoral and/or Popliteal Peripheral Artery Disease. Abbreviations: DCB, drug-coated balloon; PTA, percutaneous transluminal angioplasty; SFA, superficial femoral artery; TLR, target lesion revascularization; mo, months.

Figure 4

Comparison of TLR at 12 months in clinical trials of DCB vs PTA in BTK lesions. Notes: **P≤0.01; ***P≤0.001. DEBELLUM, Lower Limb Multilevel Treatment with Drug-Eluting Balloon Trial; DEBELLUM*1, 75% ATK and 25% BTK; DEBATE-BTK, Drug-Eluting Balloon in Peripheral Intervention for Below the Knee Angioplasty Evaluation Trial; IN.PACT DEEP, Study of IN.PACT Amphirion™ Drug Eluting Balloon vs Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia; BIOLUX-PII, BIOTRONIK’s First-in-Men Study of the Passeo-18 LUX Drug Releasing PTA Balloon Catheter vs the Uncoated Passeo 18 Balloon Catheter in Subjects Requiring Revascularization of Infrapopliteal Arteries. Abbreviations: BTK, below the knee; DCB, drug-coated balloon; ns, not significant; PTA, percutaneous transluminal angioplasty; TLR, target lesion revascularization.

Figure 5

Comparison of TLR at 12 months in clinical trials with DCB vs PTA in ISR of the SFA. Notes:*P≤0.05; ***P≤0.001. DEBATE ISR, Trial Drug Eluting Balloon in Peripheral Intervention for In-Stent Restenosis; FAIR, Drug Eluting Balloon vs PTA for Superficial Femoral Artery In-Stent Restenosis Trial; COPA CABANA trial, Cotavance™ Paclitaxel Coated Balloons vs Uncoated Balloon Angioplasty for Treatment of In-Stent Restenosis in SFA and the Popliteal Arteries. Abbreviations: DCB, drug-coated balloon; ISR, in-stent restenosis; PTA, percutaneous transluminal angioplasty; SFA, superficial femoral artery; TLR, target lesion revascularization.

Figure 6

Comparison of TLR at 12 months in clinical trials combining debulking and DCB in the SFA. Notes:**P≤0.01. DEFINITIVE-AR, Study of the SilverHawk/TurboHawk Plaque Excision Systems Used With SpiderFX to Treat Calcified Peripheral Arterial Disease. Abbreviations: DCB, drug-coated balloon; ns, not significant; SFA, superficial femoral artery; TLR, target lesion revascularization.