Reduced-Dose Paclitaxel Balloon Boosts 2-Year Femoral Artery Patency

December 05, 2018

Superior 1-year patency rates previously observed in the periphery with the Stellarex (Spectranetics) drug-coated balloon (DCB), compared with an uncoated balloon, extend to at least 2 years, suggests a new report from the ILLUMENATE European Randomized Clinical Trial (ILLUMENATE EU RCT).

In about 300 patients with superficial femoral artery (SFA) or popliteal artery lesions treated with the paclitaxel-coated Stellarex or an uncoated balloon, patency was maintained at that late follow-up in 75.9% and 61.0% of cases, respectively (= .025).

The rate of clinically driven target lesion revascularization (TLR) was lower with the Stellarex, at 12.1% vs 30.5%, respectively (P < .001), notes the study's 2-year outcomes report published online December 3 in JACC: Cardiovascular Interventions.

The Stellarex is coated with paclitaxel at a lower concentration than that in another DCB, the IN.PACT Admiral DCB (Medtronic), that has demonstrated similarly superior long-term outcomes compared with an uncoated percutaneous transluminal angioplasty (PTA) balloon.

Another DCB coated with paclitaxel at a reduced concentration, the Lutonix (Bard), failed to show a short- or long-term patency difference over a standard PTA balloon in its major randomized trial.

The trials representing the three DCBs were fairly well matched in terms of patient mix and target-vessel and target-lesion characteristics, observed lead author Marianne Brodmann, MD, Medical University Graz, Austria, in an email to theheart.org | Medscape Cardiology.

Still, she noted, although the three devices deliver the same antiproliferative agent, they differ in their drug-bearing excipient coatings and, therefore, in paclitaxel target-lesion absorption characteristics.

Brodmann said the key message from ILLUMENATE EU RCT is that Stellarex, but not the other low-paclitaxel-dose DCB Lutonix, is able to achieve long-term SFA patency similar to that of the IN.PACT balloon, despite the latter's 75% greater paclitaxel concentration.

The current findings are "proof that a lower-than-conventional drug dose DCB such as Stellarex can produce excellent outcomes, with vessel patency rates significantly superior to standard PTA, sustained though 2 years," she said. "Improved efficacy was demonstrated without any safety trade-off."

The current trial's 2-year findings are consistent with its previously published primary results at 1 year, as well as 12-month results from the corresponding American ILLUMENATE 12-Month Pivotal Trial.

In clinical practice, cautions David J. Cohen, MD, MSc, it's challenging to compare the DCBs because their trials have pitted them against standard PTA balloons, not against each other or against drug-eluting stents (DES). Cohen, not associated with the current study, is director of research at Saint Luke's Mid America Heart Institute, Kansas City, Missouri.

Speaking with theheart.org | Medscape Cardiology, he proposed that the DES evidence base in the periphery has charged ahead of DCBs with the recent results of the IMPERIAL trial, which showed a 12-month patency advantage for the Eluvia (Boston Scientific) DES compared with another DES frequently used in the SFA, the Zilver PTX (Cook Medical).

But, "the main reason that the drug-coated balloons have really been appealing is a general perception in peripheral interventions that if you can avoid a stent in the long run, it's a good thing." If no metal is left behind, it "makes repeat treatment a bit easier."

Still, in the periphery, "even the best of devices seem to have continued attrition of benefit over time," so the ILLUMENATE EU RCT researchers "are trying to establish that for whatever reason, whether it be the dose or very likely the excipient, they've achieved a measure of durability."

An editorial accompanying the report says the trial "adds to the available body of safety data on DCBs and suggests that the Stellarex DCB has an evolved synergistic combination of excipient and drug dosing that permits a lower drug dose to be effective."

The authors "allude to potential toxicity of a higher dose of paclitaxel from local effects and the potential for distal embolization. However, there have been no data published to date to suggest that paclitaxel dose toxicity is of clinical concern among the commercially available DCBs," write Andrew J.P. Klein, MD, Piedmont Heart Institute, Piedmont Healthcare, Atlanta, and Dmitriy N. Feldman, MD, Weill Cornell Medical College and New York–Presbyterian Hospital, New York City.

"Given a lack of randomized head-to-head DCB trials, cautious direct comparison among DCBs should be made," they write.

ILLUMENATE EU RCT randomized 294 patients in a 3-to-1 ratio to treatment of SFA or popliteal lesions with the Stellarex or an uncoated PTA balloon, and followed them for a median of 1035 and 1040 days, respectively. About 90% of patients in both groups were on antiplatelet agents at 24 months, the report notes.

ILLUMENATE EU RCT Outcomes at 2 Years: Stellarex vs Uncoated Balloon
End Points Stellarex, % Uncoated Balloon, % P Value
Primary patencya 75.9 61.0 .025
Composite safety end pointb 87.9 69.5 .001
Clinically driven TLR 12.1 30.5 <.001
All-cause mortality 6.5 5.1 1.00
Major adverse events 14.0 31.7 .002
a. Absence of target-lesion restenosis by duplex ultrasonography plus freedom from clinically driven TLR

b. Freedom from device- and procedure-related death at 30 days and from target-limb amputation and clinically driven TLR through 2 years.

There were no major limb amputations in the study.

Solely among target-lesion sites that developed restenosis, the time to loss of patency averaged 440 days for the DCB and 311 days for the uncoated balloon.

After exclusion of target lesions that were subsequently stented, which amounted to 15% of those in the DCB group and 11% of those in the uncoated-balloon group, the 2-year patency rates were 77.1% and 60.0%, respectively (  = .018).

Although DCBs might be the mostly commonly used interventional device in the SFA, Cohen noted, there's no one device or technique considered first-line as a standard of care.

"The standard of care is variable; that's the challenge." It's acceptable to use a balloon alone, or balloon followed by stenting if the initial result is suboptimal, or a DCB alone, or a DES, or percutaneous atherectomy followed by a balloon or stent, he said.

"Currently all of these approaches are used, and different practitioners are more attracted to one versus another."

Randomized controlled trials are needed to compare DCB and DES in for femoropopliteal lesions, write Klein and Feldman, "as well as DCB pretreatment prior to DES versus bare-metal stents."

The trial was sponsored by Philips Spectranetics, which reports providing additional funding for "data analysis and medical writing assistance with manuscript preparation." Brodmann is a consultant for Spectranetics, BARD, Medtronic, Intact Vascular, Surmodics, Bayer Healthcare, and Shockwave. Disclosures for the other authors are in the report. Cohen discloses consulting for Medtronic and Edwards Lifesciences and receiving research grant support from Medtronic, Edwards Lifesciences, Abbott Vascular, Boston Scientific, Corvia, V-wave, and AstraZeneca. Klein discloses being an advisory board member for Medtronic. Feldman reports no relevant relationships.

JACC: Cardiovascular Interventions. Published December 3, 2018. Report, Editorial

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