Drug-eluting balloon catheters for lower limb peripheral arterial disease: the evidence to date

Figures & data

Table 1 Randomized control trials of drug-eluting balloon for femoral–popliteal disease

Study name/GRADE	No of pt	Age (years)	Anatomical location	Lesion length (mm)	Clinical severity	Aim	Primary end points	FU	Key results
LEVANT 2 trial (2015)^Citation11/++++	476	69.2±9.4	Femoral–popliteal	84.4±48.5	IC	DEB vs standard PTA	The primary efficacy end point was primary patency of the target lesion at 12 months. The primary safety end point was a composite of freedom from perioperative death from any cause and freedom from limb-related death at 12 months	12 months	Primary patency DEB vs standard PTA (65.2% vs 52.6%; P=0.02). The proportion of patients free from primary safety events was 83.9% with DEB and 79.0% with standard PTA (P=0.005). There were no significant between-group differences in functional outcomes or in the rates of death, amputation, thrombosis, or reintervention
IN.PACT SFA I and II trial (2015)^Citation12/+++	331	67.5±9.5	Femoral–popliteal	89.4±4.85	IC	IN.PACT Admiral DEB vs standard PTA	Efficacy end point: primary patency of the target lesion at 12 months. Safety end points: 30-day mortality, limb salvage, target vessel thrombosis	12 months	DEB resulted in higher primary patency vs standard PTA (82.2% vs 52.4%; P<0.001). The rate of clinically driven TLR was 2.4% in the DEB arm compared with 20.6% in the standard PTA arm (P<0.001). There was a low rate of vessel thrombosis in both arms (1.4% after DEB and 3.7% after standard PTA; P=0.10). There were no device- or procedure-related deaths and no major amputations
DEBELLUM trial (2014)^Citation13/+++	50	66±4	Femoral–popliteal or BTK arteries	75±35	IC + CLI	DEB vs standard PTA	LLL at 6 months	6–12 months	In the femoral–popliteal region, the overall LLL was 0.61±0.8 mm for DEB vs 1.84±0.3 mm for standard PTA (P=0.02). BTK, the overall LLL was 0.66±0.9 mm (DEB) vs 1.69±0.5 mm (standard PTA) (P=0.03). The overall TLR was 12.2% for DEB and 35.3% for standard PTA (P<0.05). Amputation rate was 4% (DEB) vs 12% (standard PTA) (P=0.36). Thrombosis was 4% (DEB) vs 8% (standard PTA) (P≥0.05). Major AEs 24% (DEB) vs 60% (standard PTA) (P<0.05). ABI improved more in the DEB group: 0.81±0.3 vs 0.68±0.13 (P=0.02). Fontaine stage increased (from IIb to I) 80% DEB vs 56% standard PTA (P<0.05)
LEVANT 1 trial (2013)^Citation14/+++	101	68.5	Femoral–popliteal	81±38	IC	Lutonix DEB vs standard PTA	LLL at 6 months	92 patients at 6 months, 87 patients at 12 months, 83 patients at 24 months	LLL at 6 months 0.46 mm (DEB) vs 1.09 mm (standard PTA; P=0.016); composite 24-month major AEs 39% (DEB; including 15 TLRs, one amputation, four deaths) vs 46% (standard PTA; including 20 TLRs, one thrombosis, five deaths) (P=0.45)
DEBATE-SFA trial (2013)^Citation15/++	104	75±9	Femoral–popliteal	94±60	IC + CLI	DEB and BMS vs standard PTA and BMS	Binary restenosis at 12 months	12 months	Binary restenosis 17% (DEB and BMS) vs 47.3% (standard PTA and BMS; P=0.008); freedom from TLR 83% (DEB and BMS) vs 66.7% (standard PTA and BMS; P=0.07); restenosis 17% (DEB and BMS) vs 47.3% (standard PTA and BMS; P=0.008); LLL 0.86 mm (DEB and BMS; MQR 0.8–0.94) vs 1.68 mm (standard PTA and BMS; MQR 1.6–4.2; P=0.001); no major amputation in either group
PACIFIER trial (2012)^Citation16/+++	85	71±7	Femoral–popliteal	70±53	IC	DEB vs standard PTA	LLL at 6 months	6 months	DEB was associated with lower LLL (−0.01 mm [95% CI, −0.29; 0.26] vs 0.65 mm [0.37; 0.93]; P=0.001) and fewer binary restenosis (three [8.6%] vs eleven [32.4%]; P=0.01). Fewer major AEs for DEB vs standard PTA up to 12 months (three [7.1%] vs 15 [34.9%]; P<0.01) and TLR (three [7.1%] vs 12 [27.9%]; P=0.02)
THUNDER trial (2008)^Citation17/+++	154	68±8	Femoral–popliteal	74±65	IC	DEB vs standard PTA vs PTA with paclitaxel dissolved in contrast medium	LLL at 6 months	6 months	LLL at 6 m 0.4 mm (DEB) vs 1.7 mm (standard PTA) vs 2.2 mm (paclitaxel/contrast PTA) (P=0.001 DEB vs standard PTA; P=0.11 DEB vs paclitaxel/contrast PTA); TLR at 6 m 4% (DEB) vs 37% (standard PTA; P=0.001); TLR at 24 m 15% (DEB) vs 52% (standard PTA; P<0.001)
FemPac trial (2008)^Citation18/+++	87	68.7	Femoral–popliteal	40±21	IC	DEB vs standard PTA	LLL at 6 months	128 angio FU at 6 months, 146 clinical FU at 6 months	Less LLL in the DEB group (0.5±1.1 vs 1.0±1.1 mm; P=0.031). TLR was lower in the DEB group than in control subjects (three of 45 vs 14 of 42 patients; P=0.002). Improvement in Rutherford class was greater in DEB (P=0.045), whereas the improvement in ABI was not different. The difference in TLR between treatment groups was maintained up to >18 months. No AEs were assessed as related to balloon coating

Note: Quality of study as per GRADE system:

++++ high

+++ moderate

++ low

+ very low.

Abbreviations: ABI, ankle brachial index; AE, adverse event; BMS, bare metal stent; BTK, below the knee; CLI, critical limb ischemia; DEB, drug-eluting balloon; FU, follow-up; GRADE, Grades of Recommendation Assessment, Development, and Evaluation; IC, intermittent claudication; LLL, late lumen loss; m, months; MQR, median quartile range; pt, patients; PTA, percutaneous transluminal angioplasty; TLR, target lesion revascularization.

Table 2 Randomized control trials and registry of drug-eluting balloon for infrapopliteal disease

Study name/GRADE	No of pt	Age, mean ± SD	Anatomical location	Clinical severity	Lesion length (mm), mean ± SD	Aim	Primary end points	FU	Key results
IDEAS trial (2014)^Citation22/+++	50	69±8	Infrapopliteal	IC + CLI	DEB: 148±56.7; DES: 127±46.5	DEB vs DES	Target lesion restenosis >50% assessed by digital angiography at 6 months	6 months	At 6 months, five patients died (two in DEB vs three in DES; P=1.00) and three suffered a major amputation (one in DEB vs two in DES; P=1.00). Binary (>50%) angiographic restenosis rate was significantly lower in DES (seven of 25 [28%] vs eleven of 19 [57.9%] in DEB; P=0.0457). There were no significant differences with regard to TLR (two of 26 [7.7%] in DES vs three of 22 [13.6%] in DEB; P=0.65). Positive vessel wall remodeling was observed in three cases in the DEB arm (three of 19 [15.8%] vs zero of 19 [0%] in DES; P=0.07)
DEBELLUM trial (2014)^Citation13/+++	50	66±4	Femoral–popliteal or infrapopliteal	IC + CLI	75±35	DEB vs standard PTA	LLL at 6 months	6–12 months	In the femoral–popliteal region, the overall LLL was 0.61±0.8 mm for DEB vs 1.84±0.3 mm for standard PTA (P=0.02). BTK, the overall LLL was 0.66±0.9 mm (DEB) vs 1.69±0.5 mm (standard PTA) (P=0.03). The overall TLR was 12.2% for DEB and 35.3% for standard PTA (P<0.05). Amputation rate was 4% (DEB) vs 12% (standard PTA) (P=0.36). Thrombosis was 4% (DEB) vs 8% (standard PTA) (P≥0.05). Major AEs 24% (DEB) vs 60% (standard PTA) (P<0.05). ABI improved more in the DEB group: 0.81±0.3 vs 0.68±0.13 (P=0.02). Fontaine stage increased (from IIb to I) 80% DEB vs 56% standard PTA (P<0.05)
DEBATE-BTK trial (2013)^Citation23/+++	132 (158 lesions)	74±9	Infrapopliteal	CLI (pt with diabetes)	129±83	DEB vs standard PTA	Binary in-segment restenosis at 1-year angiographic or ultrasonographic FU	12 months	Binary restenosis, assessed by angiography in >90% of patients, occurred in 20 of 74 lesions (27%) in the DEB group compared with 55 of 74 lesions (74%) in the standard PTA group (P<0.001). TLR, DEB 12 (18%) vs standard PTA 29 (43%; P=0.002); and target vessel occlusion, DEB 12 (17%) vs standard PTA 41 (55%; P<0.001). Only one major amputation occurred in the standard PTA group (P=0.9)
IN.PACT DEEP triala,^Citation24	358		Infrapopliteal	CLI	102±129	DEB vs standard PTA	Clinically driven TLR and LLL at 12 months. All-cause mortality, major amputation, and clinically driven TLR at 6 months served as the primary safety end points	12 months	Primary efficacy results of DEB vs standard PTA were clinically driven TLR of 9.2% vs 13.1% (P=0.291) and LLL of 0.61±0.78 mm vs 0.62±0.78 mm (P=0.950). Primary safety end points were 17.7% vs 15.8% (P=0.021) and met the noninferiority hypothesis. A safety signal driven by major amputations through 12 months was observed in the DEB arm vs the standard PTA arm (8.8% vs 3.6%; P=0.080)
Leipzig Registry (2011)^Citation21/++	104	73.6±6.7	Infrapopliteal	IC + CLI	173±87	DEB for long infrapopliteal lesion	Binary in-segment restenosis at 3 months angiographic follow-up. Clinical improvement was defined as marked (50%) reduction in ulcer size or depth or increase of at least one Rutherford–Becker category	3 months angio FU, 3 months and 12 months clinical assessment	Angiography in 84 treated arteries showed a restenosis in 27.4% at 3 months. During a follow-up period of 378±65 days, one patient was lost and 17 died. Of the 91 limbs remaining in the analysis, clinical improvement was present in 83 (91.2%). Complete wound healing occurred in 74.2%, whereas major amputation occurred in four patients, resulting in limb salvage of 95.6% for patients with CLI

Notes:

a Stopped prematurely. Quality of study as per GRADE system

++++ high

+++ moderate

++ low

+ very low.

Abbreviations: ABI, ankle brachial index; AE, adverse event; BTK, below the knee; DEB, drug-eluting balloon; CLI, critical limb ischemia; DES, drug-eluting stent; FU, follow-up; GRADE, Grades of Recommendation Assessment, Development, and Evaluation; IC, intermittent claudication; LLL, late lumen loss; m, months; pt, patients; PTA, percutaneous transluminal angioplasty; TLR, target lesion revascularization.

Figure 1 Risk of bias graph for the studies included in this review.

Figure 2 Risk of bias summary: review authors’ judgments about each risk of bias item for each included study.

Note: +, low risk; ?, unclear risk; −, high risk.

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