Pair of Studies Support Paclitaxel-Eluting Devices for Treating Femoropopliteal Disease

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Local delivery of paclitaxel for the treatment of femoropopliteal artery disease—whether by balloon or stent—appears to offer lasting benefit, according to 2 registry studies published in the March 2013 issue of JACC: Cardiovascular Interventions.

An Italian study, previously presented in November 2011 at the Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco, CA, looked at paclitaxel-eluting balloon implantation in de novo lesions, while the Zilver PTX Global Registry focused solely on patients receiving paclitaxel-eluting stents (PES) for in-stent restenosis. Both obtained follow-up through 2 years.

Italian Registry Backs Balloons

Antonio Micari, MD, PhD, of Maria Eleonora Hospital (Palermo, Italy), and colleagues enrolled 105 patients (n = 114 lesions) with Rutherford class 2 to 4 disease due to femoropopliteal lesions. Treatment consisted of the In.Pact Admiral PEB (Medtronic, Frauenfeld, Switzerland) and provisional stenting, which was required in 12.3% of lesions.

Of the 98 patients with long-term follow-up of 27 ± 3 months, Kaplan-Meier curves indicated that, at 2 years, primary patency was maintained in 71 patients (72.4%) and secondary patency in 89 patients (84.7%). Major adverse events occurred at an overall rate of 17.5%, including death (2.2%), amputation (1.0%), and TLR (14.3%). Changes in ankle-brachial index (ABI) were maintained at 0.88 (vs. 0.86 at 12 months and 0.56 at baseline; P < 0.001). Results for absolute claudication distance, Rutherford class, and quality of life-related functional measures also were positive (P < 0.001 for all).

While the results are favorable, the paper adds a word of caution, noting that outcomes were assessed at fixed time points of 1 and 2 years. “[H]ence overall patient benefit, besides due to the drug-eluting balloon effect, might likely have been impacted also by the reported re-interventions,” Dr. Micari and colleagues write. Moreover, uncertainty remains about the best endovascular treatment strategy for femoropopliteal artery disease, they add, with many centers still using balloon angioplasty alone or trying self-expandable BMS or DES.

Paclitaxel-eluting balloons may represent the best choice for claudicant patients, the researchers suggest. “With the unavoidable disease progress within and outside the treated lesion, [Paclitaxel-eluting balloons] represent a viable option that is less likely to impact future reinterventions when compared with any first-line stent strategy.”

Lasting Results for In-Stent Restenosis

Thomas Zeller, MD, of the Universitäts-Herzzentrum Freiburg-Bad Krozingen (Bad Krozingen, Germany), analyzed data from 108 patients (n = 119 lesions) being treated for in-stent restenosis as part of the Zilver PTX Global Registry, which evaluated the Zilver PTX stent (Cook Medical, Bloomington, IN) in 787 patients between April 2006 and June 2008.

Zilver, a self-expanding nitinol stent, received US Food and Drug Administration approval in November 2012 for the indication of improving luminal diameter in both de novo and restenotic symptomatic lesions.

In the registry’s in-stent restenosis cohort, procedural success was achieved in 98.2% of lesions with 2.1 ± 1.2 stents placed per lesion. Stent fracture was rare, occurring at a rate of only 1.2% by 1 year. Primary patency rates were 95.7% at 6 months and 78.8% at 1 year. Freedom from TLR was 96.2% at 6 months, 81.0% at 1 year, and 60.8% at 2 years. Major adverse events consisted solely of TLR, which occurred in 40 patients (37%).

At baseline, 81.1% of patients had Rutherford scores of 3 or higher, but by 2 years, 60.9% had scores of 1 or lower. The mean ABI value per limb rose from 0.60 ± 0.28 to 0.84 ± 0.22 over the same time frame (P < 0.001), and patient-reported walking distance, speed, and climbing scores improved.

“These promising results are likely due to several advantageous features of the Zilver PTX stent,” the investigators note. Local delivery of paclitaxel may prevent neointimal hyperplasia, inhibiting restenosis without simultaneously blocking re-endothelialization, they say. “Additionally, unlike other drug-eluting stents, the Zilver PTX stent has no polymers, binders, or carriers within the drug coating that might elicit potential inflammatory thrombotic reactions,” and the device does not appear vulnerable to fracture when used inside another stent.

However, Dr. Zeller and colleagues point out that other options for “this difficult-to-treat patient population” are being explored by numerous studies:

  • DEB vs. uncoated balloons in the ISAR-PEBIS, FAIR, PACUBA I, COPA CABANA, PLAISIR, and DEBATE-ISR trials
  • The Viabahn endoprosthesis (WL Gore, Flagstaff, AZ) in the RELINE trial
  • Drug-eluting balloons with or without prior photoablation in the PHOTOPAC trial
  • Laser atherectomy with balloon angioplasty in the EXCITE ISR trial
  • Photoablation alone in the PATENT trial

Local Paclitaxel Delivery Key

In an editorial accompanying the paper, Ehtisham Mahmud, MD, of the University of California, San Diego (La Jolla, CA), credits local delivery of paclitaxel for enabling good outcomes in both studies but questions “whether the drug release kinetics are such that a short exposure of paclitaxel transferred from the [paclitaxel-eluting balloon] to the vessel wall leads to a different vascular response compared with the more sustained release of the drug from the stent.”

Timing is critical in reducing vascular exposure and possible injury, he notes. Therefore, the “roles of drug concentration and carrier and diffusion kinetics also require additional understanding,” as does the potential for dual antiplatelet therapy to reduce long-term adverse events after intervention.

Bruno Scheller, MD, of the University of Saarland (Homburg, Germany), agreed in an e-mail communication that “[b]oth papers represent supporting evidence for local drug delivery in the prevention and treatment of restenosis. It works not only in the coronaries but also in peripheral arteries.”

However, Dr. Scheller emphasized balloon-based delivery as the best approach. “My personal prophecy is that the future of endovascular treatment will be avoiding any permanent implant (“leaving nothing behind”),” he told TCTMD, with drug-eluting balloons becoming standard and bioabsorbable stents used in the case of flow-limiting dissections.

“The numbers of [drug-eluting balloon] procedures are steadily increasing in Europe and many other countries outside the United States,” he reported. “At least in Germany, reimbursement for [drug-eluting balloons] in coronaries and peripheral arteries has become very attractive [as of] 2013.” He predicted that drug-eluting balloons will become available in the United States around 2015.


1. Micari A, Cioppa A, Vadalà G, et al. 2-year results of paclitaxel-eluting balloons for femoropopliteal artery disease: Evidence from a multicenter registry. J Am Coll Cardiol Intv. 2013;6:282-289.

2. Zeller T, Dake MD, Tepe G, et al. Treatment of femoropopliteal in-stent restenosis with paclitaxel-eluting stents. J Am Coll Cardiol Intv. 2013;6:274-281.

3. Mahmud E. Percutaneous revascularization for peripheral arterial disease: Paclitaxel saves the day. J Am Coll Cardiol Intv. 2013;6:290-292.



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  • Dr. Micari reports serving as a consultant to Medtronic.
  • Dr. Zeller reports receiving research grants and speaker’s bureau honoraria from Cook Medical.
  • Dr. Mahmud reports no relevant conflicts of interest.
  • Dr. Scheller reports serving as a co-inventor of patent applications for various methods of restenosis inhibition including drug-eluting balloons. He is a shareholder of InnoRa GmbH and has received lecture fees from B Braun and Medtronic.

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