DCB Match DES for Treating Coronary In-Stent Restenosis: European Registry

For coronary in-stent restenosis (ISR), drug-coated balloons (DCB) appear to perform just as well over the long term as thin-strut drug-eluting stents after accounting for differences in patient characteristics, Polish registry data suggest.

Patients whose first-time DES ISR was treated with DCB had higher 3-year rates of TLR, TVR, and a device-oriented composite (cardiac death, TLR, and target-vessel MI) in an unmatched comparison, but with propensity-score matching, these disadvantages disappeared. The findings, from the DEB-DRAGON registry, were published recently in Circulation: Cardiovascular Interventions.

Wojciech Wańha, MD, PhD (Medical University of Silesia, Katowice, Poland), the study’s lead author, told TCTMD that DEB-DRAGON provides real-world data on the efficacy of DCB, showing they are noninferior to DES. “Such knowledge can prevent implantation of a second layer of DES scaffold in the target lesion without compromising long-term outcomes,” he wrote in an email, adding that DCB can also enable shorter dual antiplatelet therapy and thus reduce the risk of bleeding.

Unlike in Europe, where a mix of DCB and DES are used to address coronary ISR, the United States has fewer options, with no fully approved DCB for use in the coronaries. However, US Food and Drug Administration has granted breakthrough device designation to several, among them Selution SLR (MedAlliance), SeQuent Please ReX (B. Braun), Virtue (Orchestra BioMed), and AGENT DCB (Boston Scientific).

Robert W. Yeh, MD (Harvard Medical School, Boston, MA), principal investigator of Boston Scientific’s AGENT IDE trial, which launched earlier this year, said the Polish data are reassuring. “It’s great to have some evidence that supports drug-coated balloons as being a great alternative to drug-eluting stents,” he commented to TCTMD.

What really excites people about drug-coated balloons is that they leave “more possibilities down the road” if restenosis arises again, he noted. “US operators have been hamstrung in a certain way by not having that option available to us.”

Fernando Alfonso, MD (Hospital Universitario de La Princesa, Madrid, Spain), pointed out that the DEB-DRAGON analysis is interesting in that it spans multiple types of DCB and thin-strut DES.

“To me, this is an important study because it further supports and provides new evidence on the value of paclitaxel-eluting balloons in patients with drug-eluting stent restenosis,” he said, adding that it’s especially informative given that the balloons aren’t approved in the United States. The good news for DCB also is in line with the 2018 European myocardial revascularization guidelines recommending both strategies (class I, level of evidence A) in patients presenting with either bare-metal or drug-eluting stent restenosis.

But a few things do give him pause, said Alfonso. The randomized RIBS IV trial, which he led, found a thin-strut everolimus-eluting stent produced better late angiographic outcomes, as well as a “small but clinically relevant difference” in TLR, compared with a paclitaxel DCB. DAEDALUS, a meta-analysis of patient-level data from 10 trials, showed similar findings.

Both he and Yeh emphasized that the DEB-DRAGON results originate from an observational data set, meaning that adjustment may not fully account for differences among patients and why clinicians made certain choices.

DEB-DRAGON

The multicenter DEB-DRAGON Registry enrolled 1,117 consecutive patients with DES ISR between 2008 and 2019. Around half received a paclitaxel DCB: Agent (Boston Scientific), Elutax (Aachen Resonance GmbH), Essential (iVascular), In.Pact (Medtronic), Pantera Lux (Biotronik), Restore DEB (Cardionovum GmbH), or SeQuent Please Neo (B. Braun). The other half were treated using DES with struts < 100 µm: Xience (Abbott), Resolute (Medtronic), Promus (Boston Scientific), Ultimaster (Terumo), Synergy (Boston Scientific), Orsiro (Biotronik), or Alex (Balton).

Although there were differences in TLR, the primary endpoint, and other outcomes in the unmatched comparison, these no longer were significant in an analysis of 268 propensity-matched pairs. Also similar—in both analyses—were the individual endpoints of cardiac death, target-vessel MI, and MI.

Outcomes at 3 Years After Treatment of DES ISR

*Cardiac death, TLR, target-vessel MI

Wańha noted that their study didn’t involve intravascular imaging, thus highlighting “our limited understanding of the mechanism of ISR.” He called for additional studies to fill this gap. Using their data, the group also intends to take a closer look at how outcomes differ between chronic and acute coronary syndromes, he added.

Editorialists Giuseppe Esposito, MD, Emanuele Barbato, MD, PhD, and Jozef Bartunek, MD, PhD (all from Cardiovascular Center Aalst, OLV Hospital, Belgium), also emphasize the need for intravascular imaging, specifically optical coherence tomography, to clarify the best strategies for preventing and then treating ISR.

“Though intravascular imaging remains costly, and in several countries not reimbursed, other imaging modalities such as preprocedural computed tomography alone or in combination with advances in routine X-ray-based fusion imaging may provide an alternative approach in understanding the biology and extent of the target lesions in the first place and optimize procedural planning of the index procedure,” they suggest.

Then, Esposito et al continue, “when preventive strategy fails and ISR occurs, intravascular lesion imaging plays [a] pivotal role in understanding the underlying mechanism, enabling [a] tailored decision on the interventional strategy,” whether that’s DCB, DES, lesion ablation, or vascular brachytherapy.

Where It Stands Now

Practice is currently mixed between DCB and DES for coronary ISR, Alfonso confirmed. Stents may be the best choice when dissection or suboptimal results occur. When there is a side branch emerging at the site of restenosis, balloons may be preferable. Also, patients at high bleeding risk may be best suited by treatment with DCB.

Alfonso highlighted the potential for ultrathin DES of < 70 µm in the ISR setting, which haven’t yet been tested. Nor are there data on which among the various DCBs performs best, he said.

The idea of less metal is attractive, Alfonso commented. “I have to admit, obviously, that if you get a very nice result with a drug-coated balloon, well, then you’ve got space for another layer in the worse cases where there is [another] restenosis.”

For Yeh, the question of how best to deal with ISR is especially important given the disparity in outcomes between patients undergoing de novo PCI versus those who receive another stent layer on top of restenosis.

As for why coronary DCB are available in Europe but not in the US, he offered a few ideas. One challenge is that “drug-eluting stents now are just so very good” in de novo PCI, said Yeh. With ISR, on the other hand, “somebody has already declared that they have failed a stent before. So now they’ve failed a stent and on top of it we don’t really want to put in a new layer. We certainly don’t want to put in a third. They go down this pathway of getting multiple layers of metal, and that becomes much more clinically compelling for why you might use a balloon in this situation.”

Yet ISR cases account for a minority of PCIs—up to 10% in the US—meaning that it can be hard to enroll patients in clinical trials, he added. Previously, the promise of metal-free, bioresorbable technology may have deterred investment in drug-coated balloons, as well. “Now that those [first-generation] bioresorbable scaffolds have gone away, at least for the short term, and there still are concerns about restenosis, I think there’s renewed interest in these, which is why you’re seeing these new trials pop up,” Yeh observed.