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Deployment of a paclitaxel-eluting balloon (PEB) followed by implantation of a bare-metal stent (BMS) is much less effective than an everolimus-eluting stent (EES) alone in de novo coronary lesions, according to a randomized study published online October 9, 2013, ahead of print in the American Heart Journal. Although the trial was halted prematurely due to safety issues, analysis of the early enrollees showed the inferiority of the PEB/BMS strategy for preventing restenosis. 

Investigators led by Italo Porto, MD, PhD, of San Donato Hospital (Arezzo, Italy), aimed to randomize 366 patients with de novo stenosis in a native coronary artery to the combination of a PEB (Elutax; Aachen Resonance, Aachen, Germany) and a cobalt-chromium BMS (Prokinetic; BIOTRONIK, Bülach, Switzerland) or an EES (Xience X; Abbott Vascular, Santa Clara, CA).

The trial was terminated early due to excess ischemia-driven TLR in the PEB/BMS arm. The current analysis is based on the first 125 patients randomized, 59 in the PEB/BMS group and 66 in the EES group.

The second-generation Elutax PEB (since replaced by newer iteration) is characterized by 2 layers of paclitaxel: 1 on the inflated balloon and 1 as a crystal powder; it contained no excipient, or eluting substance.

Outcomes Not Even Close

At 9-month follow-up, both rates of in-stent and in-segment restenosis, the primary endpoint, were markedly higher in the PEB/BMS group compared with the EES group, as were rates of ischemia-driven TLR and MACE (composite of death, MI, and ischemia-driven TLR). No difference was seen in rates of death or MI (table 1).  

Table 1. Angiographic and Clinical Outcomes at 9 Months

In addition, the first 30 consecutive patients in the PEB/BMS group underwent frequency-domain optical coherence tomography. Among the 23 patients available for analysis, out of 4,304 BMS struts, only 8 (0.2%), all in a single stent and all at the proximal stent edge, were found to be uncovered and malapposed, while 1 additional strut in another patient was uncovered but apposed. A total of 67 struts (1.5%) were found to be malapposed but covered. The percentage net volume obstruction was 35%. No evidence of geographical mismatch could be found.

Not a Class Effect

In an e-mail communication with TCTMD, Bruno Scheller, MD, of the University of Saarland (Homburg, Germany), wrote, “This trial underlines the fact that there is no class effect for drug- coated balloons.” For example, he pointed out, preclinical data comparing the PACCOCATH coating of the SeQuent Please PEB (B. Braun, Melsungen, Germany) with a similar coating on the Dior I balloon (Eurocor, Bonn, Germany) showed the latter’s inferiority in terms of neointimal proliferation (Cremers B, et al. Clin Res Cardiol. 2009;98:325-330), while an analysis from the SCAAR registry revealed inferiority of the Elutax PEB to SeQuent Please (Bondesson P, et al. EuroIntervention. 2012;8:444-449).

“For [the Elutax] balloon, I have never seen any study showing efficacy in preclinical or clinical scenarios,” he noted.

“My major concern with such bad coatings,” Dr. Scheller continued, “is that they discredit the coatings with proven efficacy and safety from randomized clinical trials. And any meta-analysis that mixes up all the different types of coatings is misleading.”

Destined to Fail?

Juan F. Granada, MD, of the CRF Skirball Research Center (Orangeburg, NY), said it is important to recognize that the study takes drug-coated balloons into unproven coronary territory. “The population [the researchers] are studying is not the one that has been shown to benefit from drug-coated balloons, which is patients with in-stent restenosis, long and/or diffuse disease, and small vessels,” he said in a telephone interview with TCTMD.

Moreover, this balloon has an inherent flaw: lack of a drug excipient, Dr. Granada said, adding that it is well known that carriers are needed to transport paclitaxel into the vessel wall. The efficacy of a given technology ultimately depends on its tissue transfer and retention capabilities, he explained, suggesting that “without a carrier and at dosage of 2 μg/mm², the tissue [drug] levels in this case may be zero.”

In addition, Dr. Granada observed, when drug-coated balloons have been successful, typically they have been used without stents. “With the combination of a stent and a paclitaxel-coated balloon, the best you are going to achieve is a poor man’s Taxus stent, with different pharmacokinetics,” he said. “Is that a positive trait? I don’t know. Right now we have phenomenal DES that are not really thrombogenic and have a very good healing profile.”

The bottom line is that the balloon’s developers “did not do their [preclinical] homework,” Dr. Granada asserted. “Elutax simply doesn’t have the technical characteristics to work.” 

Study Details 

The PEB/BMS strategy involved predilation with a conventional PCI balloon, PEB dilation (2 inflations of at least 30 seconds each), and then BMS implantation. Postdilation with the PEB was not allowed.
 

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Source:
Liistro F, Porto I, Angioli P, et al. Elutax paclitaxel-eluting balloon followed by bare-metal stent compared with Xience V drug-eluting stent in the treatment of de novo coronary stenosis: A randomized trial. Am Heart J. 2013;Epub ahead of print.

 

 

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