Editorial | Rationale and evidence base for the peripheral vascular use of drug coated balloons (DCBs)

Rationale and evidence base for the peripheral vascular use of drug coated balloons (DCBs)

Published date : 27 March 2012
Article date : 27 March 2012

Editorial by Dr Sumaira Macdonald, Consultant Vascular/Interventional Radiologist & Honorary Clinical Senior Lecturer, The Freeman Hospital, Newcastle upon Tyne

Rationale

Paclitaxel, derived from the Pacific yew, demonstrates a “class effect” regarding its impact on restenosis, with favourable results for paclitaxel-coated balloons in four randomised trials of “standard” angioplasty (PTA) versus angioplasty with DCBs and for paclitaxel eluting stents (the Cook Zilver PTX) versus PTA or bare metal stents in the superficial femoral artery. Nevertheless, the efficacy of DCB angioplasty may be dependent on the dose and formulation of the active coating. Whilst sirolimus may have important utility in localised vascular drug delivey, this drug has not yet been trialled.

The superficial femoral (SFA) and popliteal arteries are traditionally hostile territories for stent placement on account of unique haemodynamics and high resistance and low flow circuitry. It makes intuitive sense to avoid placing a rigid metal pipe in these flexible elastic vessels.

Evidence base for intermediate term outcomes

Table 1 - Randomised Trial Data

TRIAL	THUNDER	FEM-PAC	LEVANT 1	PACIFIER
DCB	Medrad/Cotavance	Medrad/Cotavance	Lutonix/Moxy	Medtronic/Inpact
Number of patients	154	87	101	91
Rutherford category	1-5	1-4
Primary endpoint	6/12 late lumen loss	6/12 late lumen loss	6/12 late lumen loss	6/12 late lumen loss
Primary outcomes	0.4+/- 1.2mm vs. 1.7+/- 1.8mm (p<0.001)	0.5+/- 1.1 vs. 1.0 +/-1.1mm (p= 0.031)	0.46mm vs. 1.09mm (p=0.016)	-0.05mm vs. 0.61mm (p=0.003)
Mean lesion length	7.5cm	6 cm	8.1cm	7cm
Diabetics	50%	47%	47%
Ca++ (mod/severe)	46%	52%	n/a
Occlusions	50%	13%	41%
Restenosis	22% 14% ISR*	27% 7% ISR	11%
12 month patency	75%	81% (6 month)	72% (6 month)

Key: *ISR = In-stent restenosis

There are published follow-up data to 24 months in both the THUNDER trial and FemPac trials, confirming sustained significant benefit as measured by binary restenosis and target vessel revascularisation (TLR) rates. The principle investigator of the Thunder trial (Gunnar Tepe) has presented five year outcomes demonstrating sustained benefit for DCBs over standard balloon PTA. The Thunder and FemPac trials employed the Medrad Cotavance system (drug paclitaxel, carrier iopramide).

The Levant 1 trial (employing the Lutonix Moxy system – the drug eluted is paclitaxel, the excipient is undisclosed) demonstrated superior outcomes in term of six month late lumen loss and follow up is ongoing. The Pacifier randomised trial (employing the Medtronic Inpact system – the drug eluted is paclitaxel, the excipient is urea) again showed superior outcomes with respect to six month late lumen loss and follow up is ongoing.

The Medrad/Cotavance DCB employs Paccocath technology, and two of the four currently available randomised trials employ this technology. The Medtronic/Inpact DCB employs Freepac technology. Medtronic have bioequivalence animal data showing no difference in porcine coronary artery lumen loss at one month between Paccocath and Freepac technologies, both being significantly better than “standard” PTA.

Ongoing and proposed studies

Levant II is an international trial with the Lutonix Moxy DCB (the system has an Investigational Device Exemption status granted by FDA). The primary efficacy end point is the one-year primary patency of the target lesion. The primary safety end point is a composite of freedom from all-cause perioperative and one-year index limb amputation, index limb re-intervention and index-limb-related death.

The SPORTS study (principle investigator Gunnar Tepe) comprises a randomised comparison of the Cook Zilver PTX stent versus the Medtronic InPact DCB. The Rock trial (principle investigators Gunnar Tepe and Thomas Zeller) is an ongoing randomised comparison of DCB plus rotational atherectomy versus DCB plus stenting versus PTA in highly calcified and long occlusions. This trial highlights the adjunctive use of DCBs, in addition to their potential utility in definitive lesion treatment.

In total there are 8 randomised trials and four registries either enrolling or projected which evaluate the Medtronic InPact DCB. Medrad/Cotavance have five randomized trials in the pipeline, Cook have one on-going randomised trial with the Advance 18PTX balloon (drug paclitaxel, no excipient) and EuroCor have three ongoing randomised trials with the Dior/Freeway balloons (drug paclitaxel, excipient shellac).

Disadvantages of DCBs

Suboptimal angioplasty result

Without placement of a permanent implant, there will be a number of cases in which there results a suboptimal lumen or a flow-limiting dissection. Lesion length, calcification and the presence/proportion of chronic total occlusions may impact on the technical outcome of primary DCB angioplasty.

Cost

DCBs cost substantially more than standard angioplasty balloons but in the UK, they feature on the “Excluded Devices” list and as such, are reimbursed by the commissioning bodies. Also, the cost-benefit advantage associated with a procedure that significantly reduces restenosis and thus the potential re-intervention rate must be acknowledged.

Currently available DCBs

Table 2 - DCBs – currently available and proposed

Company	DCB	STATUS	DRUG	CARRIER	TRIALS
Biotronik	Passeo (18) Lux	Available	Paclitaxel	BTHC*	PEPPER (coronaries) BIOLUX P-I (fem-pop; on-going)
COOK	Advance 18 PTX	Proposed	Paclitaxel	Undisclosed	SFA trial on-going
Eurocor	Freeway 14 & 35	Available	Paclitaxel	Shellac (resin)	Fem-pop trial on-going
Lutonix	Moxy	Available	Paclitaxel	Undisclosed	2 coronary trials, LEVANT 1, LEVANT 2 on-going
Medrad	Cotavance	Available	Paclitaxel	Ultravist 370 (contrast)	FEM-PAC, THUNDER (Copa Cabana, Canal, Euro-Canal, River, Definitive LE on-going)
Medtronic/Invatec	INPACT Admiral, Pacific & Amphirion	Available	Paclitaxel	Urea	Inpact SFA, Inpact below the knee Leipzig registry; on-going

Key: *BTHC = Butyryl-tri-hexyl Citrate (an additive in blood bags to keep the crystalline structure of the plastic malleable – it degrades to citric acid and alcohol)

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