Drug-Eluting Balloon: Best Option for in-Stent Restenosis?

January 23, 2013

LONDON — Angioplasty with a drug-eluting balloon (DEB) is better for the treatment of in-stent restenosis than currently employed methods--implantation with a drug-eluting stent (DES) or simple angioplasty--the authors of a new meta-analysis say [1]. Dr Andreas Indermuehle (University College London Hospital, UK) and colleagues report their findings in a study published online January 18, 2013 in Heart.

The need for further revascularization because of in-stent restenosis "is the bane of coronary angioplasty," the researchers explain; although DES have reduced the need for revascularization, it remains an issue. DEB represent an emerging approach for the treatment of this problem, and these devices are increasingly being employed, but their use is based on a number of small studies that, while encouraging, have limited statistical power regarding clinical end points, they note.

Hence, they decided to perform a meta-analysis, the first to examine this issue; the results show the DEB "is a good option to treat in-stent restenosis and seems to be superior to the current standard treatment of plain old balloon angioplasty or a DES," senior author Dr Pascal Meier (Chest Hospital, London, UK) told heartwire . "DEB reduce the need for reintervention and the risk for complications, plus they are cheaper than DES and you don't end up with two layers of stents." For these reasons, Meier believes DEB "should be the first option" for in-stent restenosis and that guidelines should change, making DEB "a strong recommendation" for in-stent restenosis. Currently, guidance from American College of Cardiology/American Heart Association/Society for Cardiac Angiography and Interventions and the European Society of Cardiology advise use of DES for in-stent restenosis regardless of whether the initial stent was a bare-metal stent or a DES, he and his colleagues note, but "the evidence for this recommendation is weak."

 
DEBs reduce the need for reintervention and the risk for complications, plus they are cheaper than DES.
 

But two other experts in the field, not involved with this meta-analysis, feel this conclusion is premature. Dr Jan Piek (Academic Medical Center, University of Amsterdam, the Netherlands) told heartwire : "It's fair to conclude there is certainly a place for drug-eluting balloons for in-stent restenosis, and we can say that DEB are better than plain angioplasty and just as good as using a first-generation DES." But current clinical practice is to use a newer-generation DES (eg, everolimus eluting) to treat in-stent restenosis, he says, although he acknowledges this is not based on any strong evidence. "To change guidelines we need to wait for the results of more contemporary, ongoing trials, comparing DEB with newer, second-generation DES," he asserts.

 
To change guidelines we need to wait for the results of more contemporary, ongoing trials, comparing DEB with newer, second-generation DES.
 

Dr Dennis Ko (Sunnybrook Health Sciences Center, Toronto, ON) agrees. "DEB are better than plain old balloon angioplasty, that's quite reasonable, but at this time I'm not sure if the evidence is strong enough to say that for everybody who has in-stent restenosis the DEB would be the choice of treatment." Similar to Piek, he points out that the studies examined in the meta-analysis looked at treatment of in-stent restenosis using the first-generation Taxus (paclitaxel-eluting) stent (Boston Scientific) and that he currently treats in-stent restenosis with a newer-generation DES. "I would be a bit hesitant to change my practice--and the guidelines--based on the small number of studies in this meta-analysis." Like Piek, he says the results from the ongoing contemporary trials will be pivotal in guiding treatment decisions.

DEB Significantly Reduce Main End Points Compared With DES, Balloon Angioplasty

The review included five studies with a total of 801 patients who had originally received either a bare-metal stent (two studies) or a first-generation DES (three studies) and had an in-stent restenosis. Patients were subsequently treated with a DEB compared with either balloon angioplasty or a first-generation DES (Taxus Liberté, Boston Scientific); the latter two both acted as the control groups in the meta-analysis. Follow-up ranged from one to five years. The main end points were major adverse cardiac events (MACE), target lesion revascularization (TLR), binary in-segment restenosis, stent thrombosis, MI, and mortality.

DEBs are currently available in Europe and Canada but are not US FDA approved. Two DEBs were used in the five trials assessed in this review; both were paclitaxel-eluting (Paccocath DEB, Bayer and SeQuent Please, B Braun).

Most end points were significantly reduced for DEB compared with the control groups. For MACE, the relative risk was 0.46 for DEB compared with controls (p<0.001), for TLR it was 0.34 (p=0.006), and for angiographic in-segment restenosis it was 0.28 (p<0.001). There was also a lower mortality with DEB compared with the control groups (RR 0.48; p=0.034), and the incidence of MI was numerically lower although not statistically significant (RR 0.68; p=0.337). There was no difference between the groups in terms of stent thrombosis, however, and the authors caution that "the results of MI, stent thrombosis, and death need to be interpreted with care, since the meta-analysis might be too small to detect statistical differences in such rare events."

Meier said that, in subgroup analysis, DEB were slightly more effective in treating in-stent restenosis after initial implantation of a bare-metal stent than a DES; DEB and DES seemed equally effective for treating in-stent restenosis after DES, but the former avoids the problem of multiple layers of stents and is less expensive, he notes. And the next generation of DEB will likely have improved drug-delivery properties and so "may therefore be even more effective," he and his colleagues point out.

DEB Could Become "Part of Armamentarium" for In-Stent Restenosis; Time Will Tell

Piek and Ko say that Meier does have a point when it comes to highlighting the problems associated with putting a stent within a stent. "It is another layer of metal and, especially when you have side branches, it's not very advantageous," Piek noted, adding, "This could be a good argument, based on this meta-analysis, for using DEB in in-stent restenosis of DES, while we await the results of the contemporary trials."

Ko notes that the ISAR-DESIRE 3 trial, not included in this meta-analysis, showed that drug-eluting balloons were noninferior to a paclitaxel-eluting stent for in-stent restenosis of mainly newer-generation limus-eluting stents and that both were superior to plain angioplasty.

 
There are a lot of permutations of what you can do to treat this problem, and the authors are correct that we don’t have great evidence for using a stent within a stent.
 

"There are a lot of permutations of what you can do to treat this problem, and the authors are correct that we don't have great evidence for using a stent within a stent. The DEB could become part of the armamentarium, but it's difficult to say that this meta-analysis is the definitive study to guide treatment," Ko concludes.

Ongoing trials of contemporary treatment for in-stent restenosis include the DARE trial, assessing the SeQuent Please DEB vs the newer-generation Xience Prime DES (Abbott Laboratories), and RIBS IV, comparing a paclitaxel-eluting DEB and an everolimus-eluting stent.

The authors report no conflicts of interest. Ko reports no conflicts of interest.

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