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

Figures & data

Table 1 Early clinical trials of DCB vs PTA in femoropopliteal lesions

Femoropopliteal RCT	THUNDER^Citation14		FemPac^Citation15		PACIFIER^Citation16		LEVANT I^Citation17
DCB type used	Cotavance/Paccocath®		Cotavance/Paccocath®		IN.PACT™ Pacific		Moxy/Lutonix®
	DCB	PTA	DCB	PTA	DCB	PTA	DCB	PTA
Characteristics
Number of patients (n)	48	54	45	42	41	44	49	52
Diabetics (%)	50	46	40	55	43	28	45	50
CLI (%)			4	7	4	0	6	8
Lesion length (mm)a	75±62	74±65	57	61	7±53	66±55	81±37	80±38
De novo lesion (%)	63	83	64	67	68	83	90	88
Total occlusion (%)	27	26	13	19	23	38	41	42
Calcified lesion (%)	50	52	53	52	64	66
Bailout stenting (%)	4	22	9	14	21	34	2.7	15.8
6 months
Improvement RU	√	√	Yes	√	√	√	√	√
Improvement ABI	√	√
12 months
Improvement RU			√	√			√	√
Improvement ABI							√	√

Notes: √ Indicates significant improvement

a Data presented as mean ± standard deviation. Cotavance/Paccocath® DCB (Medrad, Bayer Healthcare, Berlin, Germany); Moxy/Lutonix® DCB (BARD Peripheral Vascular, Inc, Tempe, AZ, USA); IN.PACT™ Pacific DCB (Medtronic GmbH, Meerbusch, Germany); FemPac, Femoral Paclitaxel Randomized Pilot Trial – Inhibition of Restenosis in Femoropopliteal Arteries: Paclitaxel-Coated vs Uncoated Balloon; LEVANT I, Trial Comparing the Lutonix Catheter vs Standard Balloon Angioplasty for Treatment of Femoropopliteal Arteries With and Without Stenting; 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. Adapted with permission from Herten M, Schönefeld E, Stahlhoff S, Schwindt A, Torsello GB. Drug-coated balloons in the treatment of femoro- and infra-popliteal lesions. Interv Cardiol. 2015;7(4):353–370.⁷²

Abbreviations: ABI, ankle-brachial index; CLI, critical limb ischemia; DCB, drug-coated balloon; PTA, percutaneous transluminal angioplasty; RCT, randomized controlled trial; RU, Rutherford classification.

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.

Table 2 Recent clinical trials of DCB vs PTA and registries of DCB use in the SFA

Femoropopliteal RCT	IN.PACT SFA^Citation20		LEVANT II^Citation19		ILLUMENATE FIH^Citation21
DCB type used	IN.PACT™ Admiral		Lutonix®		Stellarex™
	DCB	PTA	DCB	PTA	DCB
Characteristics
Number of patients (n)	220	111	316	160	50/58
Diabetics (%)	41	49	43	43	34
CLI (%)	5	5	8	8	2
Lesion length (mm)a	89±49	88±51	63±41	63±40	72±47
De novo lesion (%)	95	95			100
Total occlusion (%)	26	20	21	22	12
Calcified lesion (%)			59	57	62
Severe calcification (%)	8	6
Bailout stenting (%)	8	13	3	7	8
12 months
Improvement RU	√	√	Yes	√
Improvement ABI	Yes	√

Notes: √ Indicates significant improvement.

a Data presented as mean ± standard deviation. IN.PACT™ Admiral DCB (Medtronic GmbH, Meerbusch, Germany); Lutonix® DCB (BARD Peripheral Vascular, Inc, Tempe, AZ, USA); Stellarex DCB™ (Spectranectrics, Colorado Springs, CO, USA); 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. Adapted with permission from Herten M, Schönefeld E, Stahlhoff S, Schwindt A, Torsello GB. Drug-coated balloons in the treatment of femoro- and infra-popliteal lesions. Interv Cardiol. 2015;7(4):353–370.⁷²

Abbreviations: ABI, ankle–brachial index; CLI, critical limb ischemia; DCB, drug-coated balloon; LLL, late lumen loss; PTA, percutaneous transluminal angioplasty; RCT, randomized controlled trial; RU, Rutherford classification; SFA, superficial femoral artery.

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.

Table 3 Clinical trials of DCB vs PTA in BTK lesions

BTK RCT	DEBELLUM^*^Citation25		DEBATE-BTK^Citation27		IN.PACT DEEP^Citation26		BIOLUX-PII^Citation28
DCB type used	IN.PACT™ Amphirion		IN.PACT™ Amphirion		IN.PACT™ Amphirion		Passeo-18 Lux
	DCB	PTA	DCB	PTA	DCB	PTA	DCB	PTA
Characteristics
Number of patients (n)	25	25	65	67	239	119	36	36
Diabetics (%)	52	36	100	100	76	69	61	72
CLI (%)	36	40	100	100	100	99	78	78
Lesion length (mm)a	75±35	74±35	129±83	131±79	101±9I	129±95	113±88	115±87
De novo lesion (%)	100	100	100	100	93	96
Total occlusion (%)	21	22	77	82	39	46
Calcified lesion (%)					75	78	36	11
Severe calcification (%)					14	11
12 months
Improvement RU			Yes	√
Improvement ABI			Yes	√	√	√
Amputation rate (%)	4.0	12.0	0	1.5	8.8	3.6	3.3	5.7

Notes: √ Indicates significant improvement.

a Data presented as mean ± standard deviation. IN.PACT™ Amphirion DCB (Medtronic GmbH, Meerbusch, Germany); Passeo-18 Lux DCB (Biotronik SE and Co, KG, Berlin, Germany); DEBELLUM, Lower Limb Multilevel Treatment with Drug-Eluting Balloon Trial; DEBELLUM^*I, 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. Adapted with permission from Herten M, Schönefeld E, Stahlhoff S, Schwindt A, Torsello GB. Drug-coated balloons in the treatment of femoro- and infra-popliteal lesions. Interv Cardiol. 2015;7(4):353–370.⁷²

Abbreviations: ABI, ankle–brachial index; ATK, above the knee; BTK, below the knee; CLI, critical limb ischemia; DCB, drug-coated balloon; LLL, late lumen loss; PTA, percutaneous transluminal angioplasty; RCT, randomized controlled trial; RU, Rutherford classification.

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.

Table 4 Clinical trials of DCB vs PTA in ISR of the SFA

Femoropopliteal RCT and registry	Italian registry^Citation31	DEBATE ISR^Citation35		FAIR^Citation34		COPA CABANA^Citation33
DCB type used	IN.PACT™	IN.PACT™ Admiral		IN.PACT™ Admiral		Cotavance®
	DCB	DCB	PTA	DCB	PTA	DCB	PTA
Characteristics
Number of patients (n)	39	44	42	62	57	47	41
Diabetics (%)	49	100	100	45	30	43	46
CLI (%)		75	67	4,8	10,5	8	11
Lesion length (mm)a	83±39	132±86	137±82	82±71	81±66	119±96	109±78
Lesion type (%)	ISR	ISR	ISR	ISR	ISR	ISR	ISR
Total occlusion (%)	20			24	33	18	35
Bailout stenting (%)	10,3	15,9	26,2	1,6	7,0
12 months
Improvement RU				Yes	√
Improvement ABI				√	√

Notes: √ Indicates significant improvement.

a Data presented as mean ± standard deviation. IN.PACT™ Admiral DCB (Medtronic GmbH, Meerbusch, Germany); Cotavance™ DCB (Medrad, Bayer Healthcare, Berlin, Germany); 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. Adapted with permission from Herten M, Schönefeld E, Stahlhoff S, Schwindt A, Torsello GB. Drug-coated balloons in the treatment of femoro- and infra-popliteal lesions. Interv Cardiol. 2015;7(4):353–370.⁷²

Abbreviations: ABI, ankle–brachial index; CLI, critical limb ischemia; DCB, drug-coated balloon; ISR, in-stent restenosis; LLL, late lumen loss; PTA, percutaneous transluminal angioplasty; RCT, randomized controlled trial; RU, Rutherford classification; SFA, superficial femoral artery.

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.

Table 5 Clinical trials combining debulking and DCB in the SFA

Debulking + DCB RCT	Sixt et al (2013)^Citation51		Gandini et al (2013)^Citation52		Tepe (2015)^Citation53 (DEFINITIVE AR)
Study design, systems used	DA + DCB vs DA + PTA, SilverHawk™		LA + DCB vs DCB only, TurboElite Laser, Freeway DCB®		DA + DCB vs DCB only, SilverHawk™/Turbo Hawk™, Cotavance™ DCB
	DA +DCB	DA + PTA	LA+DCB	DCB	DA+DCB	DCB
Characteristics
Number of patients (n)	29	60	24	24	48	54
CLI	42	17	100	100
Lesion length (mm)a	153±93	180±136	200±101	233±91	113	97
Lesion type	93% ISR	60% ISR	100% ISR	100% ISR
Total occlusion (%)
Severe calcification (%)			25	42	25	19
12 months
Distal embolization, n	5	7	1	2	3	0
Limb salvage (%)			92	54	100	100
Ulcer healing (%)			87	62
Amputation rate, n			8,3	45,8	0	0

Notes:

a Data presented as mean ± standard deviation. Cotavance™ DCB (Medrad, Bayer Healthcare, Berlin, Germany); Freeway DCB® (Eurocor GmbH, Bonn, Germany); SilverHawk™, TurboHawk™ Plaque Excision Systems (Covidien-EV3, Dublin, Ireland); TurboElite Laser (Spectranetics, Corporation, Leusden, the Netherlands); DEFINITIVE-AR, Study of the SilverHawk/TurboHawk Plaque Excision Systems Used With SpiderFX to Treat Calcified Peripheral Arterial Disease. Adapted with permission from Herten M, Schönefeld E, Stahlhoff S, Schwindt A, Torsello GB. Drug-coated balloons in the treatment of femoro- and infra-popliteal lesions. Interv Cardiol. 2015;7(4):353–370.⁷²

Abbreviations: CLI, critical limb ischemia; DA, directional atherectomy; DCB, drug-coated balloon; LA, laser atherectomy; ISR, in-stent-restenose; PTA, percutaneous transluminal angioplasty; RCT, randomized controlled trial; RU, Rutherford classification; SFA, superficial femoral artery.

TepeGZellerTAlbrechtTLocal delivery of paclitaxel to inhibit restenosis during angioplasty of the legN Engl J Med2008358768969918272892

 PubMed Web of Science ®Google Scholar

WerkMLangnerSReinkensmeierBInhibition of restenosis in femoropopliteal arteries: paclitaxel-coated versus uncoated balloon: femoral paclitaxel randomized pilot trialCirculation2008118131358136518779447

 PubMed Web of Science ®Google Scholar

WerkMAlbrechtTMeyerDRPaclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the randomized PACIFIER trialCirc Cardiovasc Interv20125683184023192918

 PubMed Web of Science ®Google Scholar

ScheinertDDudaSZellerTThe LEVANT I (Lutonix paclitaxel-coated balloon for the prevention of femoropopliteal restenosis) trial for femoropopliteal revascularization: first-in-human randomized trial of low-dose drug-coated balloon versus uncoated balloon angioplastyJACC Cardiovasc Interv201471101924456716

 PubMed Web of Science ®Google Scholar

HertenMSchönefeldEStahlhoffSSchwindtATorselloGBDrug-coated balloons in the treatment of femoro- and infra-popliteal lesionsInterv Cardiol201574353370

 Google Scholar

TepeGLairdJSchneiderPIN.PACT SFA Trial Investigators. Drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial femoral and/or popliteal peripheral artery disease: 12-month results from the IN.PACT SFA Randomized TrialCirculation2015131549550225472980

 PubMed Web of Science ®Google Scholar

RosenfieldKJaffMRWhiteCJLEVANT 2 InvestigatorsTrial of a paclitaxel-coated balloon for femoropopliteal artery diseaseN Engl J Med2015373214515326106946

 PubMed Web of Science ®Google Scholar

DudaSILLUMENATE FIH: direct DCB cohort – first resultsLINCLeipzig, Germany2015 Available from: http://linc2015.cloudcontrolled.com/media/15th_1_0830_Duda.pdfAccessed February 19, 2015

 Google Scholar

FanelliFCannavaleABoattaELower limb multilevel treatment with drug-eluting balloons: 6-month results from the DEBELLUM randomized trialJ Endovasc Ther201219557158023046320

 PubMed Web of Science ®Google Scholar

LiistroFPortoIAngioliPDrug-eluting balloon in peripheral intervention for below the knee angioplasty evaluation (DEBATE-BTK): a randomized trial in diabetic patients with critical limb ischemiaCirculation2013128661562123797811

 PubMed Web of Science ®Google Scholar

ZellerTBaumgartnerIScheinertDIN.PACT DEEP Trial Investigators. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trialJ Am Coll Cardiol201464151568157625301459

 PubMed Web of Science ®Google Scholar

ZellerTBeschornerUPilgerEPaclitaxel-coated balloon in infrapopliteal arteries: 12-month results from the BIOLUX P-II randomized trial (BIOTRONIK’S-first in man study of the Passeo-18 LUX drug releasing PTA balloon catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries)JACC Cardiovasc Interv20158121614162226493253

 PubMed Web of Science ®Google Scholar

StabileEVirgaVSalemmeLDrug-eluting balloon for treatment of superficial femoral artery in-stent restenosisJ Am Coll Cardiol201260181739174223040582

 PubMed Web of Science ®Google Scholar

LiistroFAngioliPPortoIPaclitaxel-eluting balloon vs. standard angioplasty to reduce recurrent restenosis in diabetic patients with in-stent restenosis of the superficial femoral and proximal popliteal arteries: the DEBATE-ISR studyJ Endovasc Ther20142111824502477

 PubMed Web of Science ®Google Scholar

KrankenbergHTublerTIngwersenMDrug-coated balloon versus standard balloon for superficial femoral artery in-stent restenosis: the randomized femoral artery in-stent restenosis (FAIR) TrialCirculation2015132232230223626446728

 PubMed Web of Science ®Google Scholar

TepeGThe Copa Cabana study: DEB vs. POBA in in-stent restenosisLINCLeipzig, Germany2015 Available from: http://linc2015.cloudcontrolled.com/media/15t_1_1620_Tepe.pdfAccessed February 19, 2015

 Google Scholar

SixtSCarpio CancinoOGTreszlADrug-coated balloon angioplasty after directional atherectomy improves outcome in restenotic femoropopliteal arteriesJ Vasc Surg201358368268623755977

 PubMed Web of Science ®Google Scholar

GandiniRDel GiudiceCMerollaSMorosettiDPampanaESimonettiGTreatment of chronic SFA in-stent occlusion with combined laser atherectomy and drug-eluting balloon angioplasty in patients with critical limb ischemia: a single-center, prospective, randomized studyJ Endovasc Ther201320680581424325697

 PubMed Web of Science ®Google Scholar

TepeGDCB + atherectomy for complex lesions: DEFINITIVE AR – final dataLINCLeipzig, Germany2015 Available from: http://linc2015.cloudcontrolled.com/media/15t_1_1005_Tepe.pdfAccessed February 19, 2015

 Google Scholar