Drug-Coated Balloons for Infrainguinal PAD

Abstract and Introduction

Abstract

Revascularization of infrainguinal peripheral artery disease has traditionally been accomplished via percutaneous transluminal angioplasty. However, long-term results have been hampered by high rates of restenosis. Along with the advent of stents, paclitaxel-coated balloons are an emerging therapeutic option for the invasive management of infrainguinal peripheral artery disease. Paclitaxel has been successful in inhibiting neointimal hyperplasia, the main mechanism for in-stent restenosis. Technological advances have facilitated the development of paclitaxel-coated balloons, which show promise in early trials for femoropopliteal stenosis relative to uncoated balloons. For infrapopliteal stenoses, the data remain scant and conflicted. Therefore, large-scale randomized clinical trials with long-term follow-up evaluating safety and effectiveness between various strategies need to be performed to determine the optimal invasive management strategy for infrainguinal peripheral artery disease.

Introduction

Since Dr Charles Dotter described the first percutaneous transluminal angioplasty (PTA) over 50 years ago, endovascular therapy has remained an important treatment option for infrainguinal peripheral artery disease (PAD).^[1] Despite numerous advances in technology over time, endovascular approaches to femoropopliteal and infrapopliteal PAD remain plagued by high rates of restenosis.^[2] Despite the effectiveness of PTA in establishing immediate revascularization, the vascular injury generated can lead to elastic recoil and plaque dissection which can lead to abrupt vessel closure.^[3]

The introduction of stents in the 1990s appeared to have solved these issues by providing a metal scaffold.^[2] However, exaggerated neointimal hyperplasia frequently led to in-stent restenosis, with multiple randomized controlled trials failing to find a long-term benefit of using stents over angioplasty.^[4–7] Rates of restenosis for both PTA and stenting due to neointimal hyperplasia vary by arterial bed and lesion length, but can approach up to 50% at 2 years regardless of intervention type.^[5,8,9]

Table 1. Summary of trials comparing drug-coated balloons versus percutaneous transluminal angioplasty for femoropopliteal stenosis.
Trial	N	Primary Outcome	Primary Outcome Result	P	Percent Reduction	Target-Lesion Revascularization	P
THUNDER²⁵	154	Late lumen loss at 6 months	0.4 mm vs 1.7 mm	<.001	76.5%	4% vs 37%	<.001
FemPac²⁷	87	Late lumen loss at 6 months	0.5 mm vs 1.0 mm	.03	50%	7% vs 33%	.01
LEVANT I⁴⁵	101	Late lumen loss at 6 months	0.4 mm vs 1.1 mm	.02	64%	13% vs 34%	—
PACIFIER⁴⁶	91	Late lumen loss at 6 months	-0.01 mm vs 0.65 mm	.01	—	7% vs 21%	.12
IN.PACT SFA²⁹	331	Primary patency at 12 months	82% vs 52%	<.001	30%	2% vs 21%	<.001

Table 2. Summary of trials comparing drug-coated balloons versus percutaneous transluminal angioplasty or drug-eluting stents for infrapopliteal stenosis.
Trial	N	Primary Outcome	Primary Outcome Result	P	Percent Reduction	Target-Lesion Revascularization	P
DEBATE-BTK⁴⁰	132	Binary in-segment restenosis at 12 months	27% vs 74%	<.001	47% (with DCB)	18% vs 43%	.01
INPACT DEEP⁴¹	358	Clinically driven target-lesion revascularization and late lumen loss at 12 months	9.2% vs 13.1% and 0.61 mm vs 0.62 mm	NS	—	9% vs 13%	NS
IDEAS⁴²	50	Target-lesion restenosis >50% at 6 months	58% vs 28%	.045	30% (with DES)	14% vs 7%	NS