IN.PACT™ Admiral™ drug-coated balloons in peripheral artery disease: current perspectives

Figures & data

Table 1 CE-marked DCBs

Device	Company	Drug	Coating/excipient	Drug dose (µg/mm^2)	FDA approval
RCT result available
IN.PACT™ Admiral™	Medtronic Vascular, Santa Clara, CA, USA	Paclitaxel	Urea	3.5	Yes
Lutonix^®	BARD, Murray Hill, NJ, USA	Paclitaxel	Polysorbate/sorbitol	2.0	Yes
Stellarex™	Spectranetics, Colorado Springs, CO, USA	Paclitaxel	Polyethylene glycol	2.0	Yes
Ranger™	Boston Scientific, Marlborough, MA, USA	Paclitaxel	Acetyl tributyl citrate 2	2.0	No
Passeo-18 Lux	Biotronik, Bülach, Switzerland	Paclitaxel	Butyryl-tri-hexyl citrate	3.0	No
SeQuent^® Please	B.Braun, Melsungen, Germany	Paclitaxel	Resveratrol	3.0	No
Under RCT vs BA
SurVeil	SurModics, MN, USA	Paclitaxel	Proprietary photolink^®	3.2	No
LEGFLOW^®	Cardionovum, Bonn, Germany	Paclitaxel	Shelloic acid	3.0	No
Luminor	iVascular, Barcelona, Spain	Paclitaxel	Organic ester	3.0	No
Other DCBs without RCT
Elutax SV	Aachen Resonance, Luxembourg, Luxembourg	Paclitaxel	Dextrane	2.2	No
BioPath (Freeway)	Biosensors, Singapore	Paclitaxel	Shelloic acid	3.0	No
Kanshas™	Terumo, Tokyo, Japan	Paclitaxel	l-Serine ethyl ester HCl	3.2	No
XTREME TOUCH	Concept Medical Inc., Surat, India	Sirolimus	Phospholipid	1.27	No

Abbreviations: BA, balloon angioplasty; CE, Conformité Européene; DCBs, drug-coated balloons; FDA, Food and Drug Administration; RCT, randomized controlled trial.

Figure 1 Representative images of histological changes after IN.PACT™ Admiral™ DCB and Lutonix^® DCB treatments, and histological scores of drug biological effects in the swine femoral artery model.

Notes: Movat Pentachrome stained sections showing cross sections of the iliofemoral arteries after IN.PACT Admiral DCB and Lutonix DCB treatments (A–H). Note proteoglycan deposition (green) peaking at 30–60 days (B, C, F and G) and decreased at long-term follow-up (90 days, D and H). Both depth (I) and circumferential (J) medial SMC loss scores at long-term follow-up (90 days) were significantly greater for IN.PACT Admiral than Lutonix DCB.
Abbreviations: DCB, drug-coated balloon; SMC, smooth muscle cell.

Table 2 Result from RCTs of currently available DCBsa

General						Lesion characteristics					Clinical outcome
DCB type	Study name	Primary endpoint	PSVr for PP	Treatment	n	Calc (%)	Severe calc (%)	CTO (%)	Lesion length (mm)	Provisional stenting (%)	PP (%)	PP P-value	TLR (%)		CD-TLR (%)	TLR P-value	LLL (mm)	LLL P-value	Emboli (%)
IN.PACT™ Admiral™	IN.PACT SFA^Citation13	12M PPa	2.4	IN.PACT Admiral	220	N/A	8	26	89	7	82	<0.001		3	2	<0.001	N/A	N/A	N/A
				BA	111		6	20	88	13	52			21	21
	MDT-2113^Citation15	12M PPa	2.4	IN.PACT Admiral	68	N/A	7	16	92	4	89	<0.001		3	3	0.012	N/A	N/A	N/A
				BA	32		9	16	89	3	48			19	19
Lutonix^®	LEVANT 1^Citation63	6M LLL	N/A	Lutonix	49	N/A	N/A	41	81	3	72	N/A		13	N/A	NS	0.46±1.13	0.02	N/A
				BA	52			42	80	16	49			22			1.09±1.07
	LEVANT 2^Citation40	12M PPa	2.5	Lutonix	316	60	10	21	63	3	65	0.02		12	N/A	0.2	N/A	N/A	0.6
				BA	160	58	8	22	63	7	53			17					1.9
Stellarex™	ILLUMINATE Pivotal and PK^Citation38	12M PPa	2.5	Stellarex	200	N/A	44	19	80	6	76	0.003		10	N/A	0.043	N/A	N/A	0.5
				BA	100		43	18	89	6	58			18					0
	ILLUMINATE EU RCT^Citation39	12M PPa	2.5	Stellarex	198	N/A	13	19	72	15	84	<0.001		N/A	6	0.01	N/A	N/A	N/A
				BA	61		10	19	71	11	61			N/A	17
Ranger™	RANGER SFA^Citation41	6M LLL	2.4	Ranger	71	90	36	34	68	21	92	0.005		6	N/A	0.5b	−0.16±0.99	0.002	N/A
				BA	34	84	22	34	60	12	64			12			0.76±1.4
Passeo-18 Lux	BIOLUX P-1^Citation42	6M LLL	N/A	Passeo-18 Lux	30	N/A	15	38	51	7	N/A	N/A		N/A	4	0.8	0.51±0.72	0.03	N/A
				BA	30				69	27	N/A			N/A	6		1.04±1.00
SeQuent^® Please	CONSEQUENT^Citation43	6M LLL	N/A	SeQuent Please P	78	N/A	N/A	23	137	14	N/A	N/A		9	N/A	0.001	0.35	0.006	N/A
			N/A	BA	75			29	126	19				31			0.72

Notes:

a Freedom from restenosis (assessed by a duplex ultrasound PSVr) and TLR.

b Twelve months f/u data demonstrated significantly less TLR in DCB compared with BA (8.5% vs 26.5%, respectively, P=0.03).

Abbreviations: BA, balloon angioplasty; calc, calcification; CD, clinically driven; CTO, chronic total occlusion; DCBs, drug-coated balloons; LLL, late lumen loss; N/A, not applicable, NS, not significant; PP, primary patency; PSVr, peak systolic velocity ratio; RCTs, randomized controlled trials; TLR, target lesion revascularization; f/u, follow up.

Figure 2 Representative images of downstream nontarget skeletal muscle and coronary band tissues from healthy swine after treatment of femoral arteries and downstream incidence of distal embolization after treatment with overlapping DCBs at 28 days follow-up.

Source: Reproduced with permission from Reprinted from Journal of Vascular and Interventional Radiology, 27, Frank D. Kolodgie, Erica Pacheco, Kazuyuki Yahagi, Hiroyoshi Mori, Elena Ladich, Renu Virmani, Comparison of Particulate Embolization after Femoral Artery Treatment with IN.PACT Admiral versus Lutonix 035 Paclitaxel-Coated Balloons in Healthy Swine, 1676-1685.e2., © 2016, with permission from Elsevier. And Reprinted from Journal of Vascular and Interventional Radiology, Sho Torii, Hiroyuki Jinnouchi, Atsushi Sakamoto, Maria E. Romero, Frank D. Kolodgie, Renu Virmani, Aloke V. Finn, Comparison of Biologic Effect and Particulate Embolization after Femoral Artery Treatment with Three Drug-Coated Balloons in Healthy Swine Model, Epub ahead of print., © 2018, with permission from Elsevier.⁶⁸

Notes: Hematoxylin and eosin stained sections showing embolic crystalline material after IN.PACT™ Admiral™ DCB (A), Ranger™ (B), and Stellarex™ (C) treatment (yellow arrows in top row) embedded in fibrin.
Abbreviation: DCBs, drug-coated balloons.

Figure 3 Primary patency and LLL at 12 months after the treatment in eight groups that were classified according to circumferential and longitudinal distribution of calcification.

Source: Reprinted by permission from Springer Nature Customer Service Centre GmbH: Springer Nature CardioVascular and Interventional Radiology Fanelli F, Cannavale A, Gazzetti M, et al. Calcium burden assessment and impact on drug-eluting balloons in peripheral arterial disease. Cardiovasc Intervent Radiol. 2014;37(4):898–907, © 2014.⁵⁹

Note: There is an inverse relationship between the primary patency and LLL with groups with severe calcification (4a and 4b).
Abbreviation: LLL, late lumen loss.

Figure 4 Representative histologic images of the biologic responses to DCB + DES, BA + DES, DCB + BMS, and DCB alone in swine iliofemoral arteries.

Source: Reprinted from Journal of Vascular and Interventional Radiology, 29, Sho Torii,Kazuyuki Yahagi, Hiroyoshi Mori, Emanuel Harari, Maria E. Romero, Frank D. Kolodgie, Brandt Young, Anthony Ragheb, Renu Virmani, Aloke V. Finn, Biologic drug effect and particulate embolization of drug-eluting stents versus drug-coated balloons in healthy swine femoropopliteal arteries, 1041–1049., © 2018, with permission from Elsevier.⁶¹

Notes: Fibrin deposition in each treatment group is demonstrated in the middle panels, whereas depth of SMC loss is demonstrated with yellow arrows in the lower panels. Mild medial SMC loss with focal proteoglycan accumulation is observed in the DCB-alone group (A–C). Moderate medial SMC loss is observed in the DCB + BMS group, with minimal fibrin around stent struts (D–F). The greatest biologic drug effect is observed in the DCB + DES (G–I) and BA + DES (J–L) groups in the form of extensive medial SMC loss and extensive fibrin around stent struts.
Abbreviations: BA, balloon angioplasty; BMS, bare metal stents; DCB, drug-coated balloon; DES, drug-eluting stents; PTA, percutaneous transluminal angioplasty; SMC, smooth muscle cell.

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