Donald Cutlip, MD, is a professor of medicine at Harvard Medical School.

Donald Cutlip, MD

Donald Cutlip, MD | Image Credit: BAIM Institute for Clinical Research

 approved Cordis’s SELUTION Sustained Limus Release (SLR) Drug-Eluting Balloon (DEB) for 

The approval was based on results from the SELUTION4ISR trial, a single blind, randomized, non-inferiority trial conducted across 48 centers in the US, Europe, Canada, and Brazil. Investigators enrolled patients >18 years with ischemia related to ISR of a previous bare-metal or drug-eluting stent (DES) and randomly assigned them in a 1:1 ratio to either the SELUTION DEB or a control strategy, which was designed as ≥80% repeat DES and ≤20% balloon angioplasty.

The trial’s primary outcome was target lesion failure, including cardiac death, target vessel myocardial infarction, or clinically driven lesion revascularization, which was assessed at 1 year in the per-protocol population. Non-inferiority was determined by whether the upper limit of the 2-sided 95% credible interval was <10%.

A total of 418 patients were assigned to either DEB (n = 210) or control (n = 208), with 390 patients per protocol (197 with DEB, 193 with control). At 12 months, target lesion failure occurred in 32 patients in the DEB arm and 28 in the control group, with an absolute risk difference of 1.7% (95% CI, -5.5% to 8.9%). Clinical follow-up is ongoing, expected to last to 5 years post-operation.

Donald Cutlip, MD, professor of medicine at Harvard Medical School and principal investigator in the SELUTION4ISR trial, sat down with the 

 editorial team to discuss the DEB’s potential for patients with ISR. In the following Q&A, Cutlip explains the SELUTION SLR DEB’s pathway through clinical trials to FDA approval, as well as its pathway forward in clinical use.


Q&A: Cutlip on the SELUTION SLR DEB’s FDA Approval for Coronary In-Stent Restenosis

Could you provide a brief overview of the SELUTION SLR Sirolimus DEB and how it received approval from the FDA?

 Well, the SELUTION SLR drug-eluting balloon, like other drug-coated or drug-eluting balloons, is really a vehicle just for delivering drug to the coronary. After the artery has been opened, we use the balloon to bring the drug there for delivery. What was needed for this study was to show safety and effectiveness, like for any new device to get FDA approval, and the solution SL four trial was designed to do that.

There's lots of interest in having sirolimus, or at least a second drug, available in drug-eluting balloons. We have paclitaxel, which is pretty easy: you can coat it on a balloon, take it up to the artery, and it gets absorbed pretty quickly. However, to allow for loss of drug on the way, you have to put a pretty high dose on. So that's what gets to the coronary artery. It hasn’t been proven, but there's been concern regarding, say, possible toxic effects of paclitaxel with a higher dose.

The way the SLR balloon works is that sirolimus is packaged into microspheres made of polymer, and then protected with a phospholipid layer, so the drug gets delivered, and then you can really dial in and be very specific about the dose you want. The dose of the balloon for sirolimus is really the same as sirolimus or everolimus might be on a drug-eluting stent. We're not putting in a higher dose. And then the polymer and the membrane protect the drug, allowing it to be in contact with the vessel wall long enough to be absorbed. Because sirolimus is not rapidly absorbed like paclitaxel, you need to have this engineering marvel to sort of get it there. I think that's novel. This is the first sirolimus balloon that we have in the U.S., and I think more credit goes to the engineers than to any of us who put the balloons in, but we're excited about it, and I think it's going to be a big addition to the toolbox for interventional cardiology.

ISR is among the most challenging scenarios in interventional cardiology. What does the availability of a sirolimus drug-eluting balloon change about how you approach ISR today?

There's been a lot of interest in using drug-coated balloons rather than putting another stent or multiple layers of stent into an ISR. However, ISR has become fairly uncommon with drug-eluting stents being so effective - we only see it now in about 10% of lesions. This is as opposed to bare metal stents, which is like ≥30%. But when it happens, it's still important, and when it happens once, it can keep happening. So that's why it's so advantageous to have a balloon that you can deliver drug and not leave more metal behind, as opposed to putting in more stents.


: Could you describe the types of ISR patients in whom you think SELUTION SLR is most likely to be particularly useful? Conversely, are there any ISR presentations where you would still strongly favor repeat DES?

We designed the trial to look at what was happening as a standard of care currently, and before we had any drug-eluting balloons at the time we designed the study, what was happening was about 80% use of another drug-eluting stent and about 20% use of plain balloon angioplasty. The problem with that is that putting in that second layer of stent, and then more on top of it, eventually you just create a problem of recurrent restenosis that you can't fix. We were the first, and probably only, trial to compare against the standard of care.

So, 80% of patients in the control arm actually received a drug-eluting stent. We didn't expect to be better than a drug-eluting stent or even necessarily as good, but we did expect to be at least as good as the standard of care and avoid that 80% drug-eluting stent use that was happening. We met that endpoint, as you know, and that's why the FDA was able to approve it. But I think more importantly that we were able to actually identify how much difference is there by not putting in that second layer. For the first restenosis, what our data show is there's about a 6-7% advantage. Drug-eluting stent did better, but at least we know how much better, so we can decide whether we want to take a chance of having maybe a 7% higher rate of recurrence to avoid that second layer of stent in almost 90% of the patients. That's a decision that a clinician will have to make with their patients because there is clearly that trade-off.

I think some would argue that maybe for that first restenosis, the initial treatment, maybe a drug-eluting stent would still be preferred at least in some, and maybe even most patients. But there are certainly many who would rather avoid that layer, either the physician or the patient. They would rather get the drug-eluting balloon and then take the drug-eluting stent next time if you're one of the 10% or so that recur.

 Does the SELUTION4ISR experience suggest that ISR should no longer be viewed as one homogeneous entity, but rather that the mechanism and anatomy of restenosis should determine the treatment strategy?

Our study actually does not show that, but we know that from other from other data. We required all patients to have imaging prior to treatment, and the point of that was to identify those types of lesions that would not best be treated just with a drug-eluting balloon. So, if you see a stent fracture, you see a stent that's not expanded. The initial stent reached the nose because it was never fully expanded. It may be better to treat that with high-pressure balloon inflation to try to get that stent expanded. It may still then be reasonable to use a drug-eluting balloon for final treatment, but it would not be without first expanding that stent. I think if you see pure neointimal hyperplasia as the mechanism, and it's the first restenosis, there again you'd have this debate: should I put a drug-eluting stent? Maybe in those cases where there's lots of neointimal hyperplasia, that may be preferred. Otherwise, a drug-eluting balloon should be a reasonable option.

The SELUTION SLR is currently approved for ISR, while a 960-patient trial is evaluating the technology against DES in de novo lesions and small coronary vessels. What would you need to see from that program before considering drug-eluting balloons for broader PCI indications?

We were involved in the design of that trial also, and our goal there again was to be non-inferior to standard of care. Standard of care there is different; it's a drug-eluting stent, so we need to be non-inferior to a drug-eluting stent. I think we would accept some margin. We would accept some slight difference as long as it meets the non-inferiority criteria. But we're really looking to be as good as a drug-eluting stent, and maybe even better over time by not having that layer of metal there in the first place. And that's going to be more of a long-term outcome.

However, the initial outcome, the one-year outcome, will be just restenosis or target lesion failure, which is mostly restenosis, and I think there's lots of excitement about that. I mean, we did the ISR study first because that seemed to be the best pathway to get the device approved and was where there was a lot of interest and excitement about having drug-eluting balloons available. I think, thanks to the SELUTION investigators in Europe who did this large, 3000-patient trial of de novo, we now know that's very safe. And so, I think in the U.S. now there's a lot more interest in that de novo indication than just for ISR.

Editors’ Note: Cutlip reports being a consultant at Celonova, MedAlliance, and Corvia, and grants/research support from Cordis and Corvia.

Cordis. SELUTION SLR PTCA Drug-Eluting Balloon FDA Approved. September 21, 2026. Accessed September 28, 2026. 

https://cordis.com/na/news/selution-slr-ptca-drug-eluting-balloon-us-fda-approval

Cutlip DE. Or2-20 | SELUTION4ISR – a randomized trial of a sirolimus-eluting balloon versus repeat drug-eluting stenting or balloon angioplasty for coronary in-stent restenosis. Journal of the Society for Cardiovascular Angiography &amp; Interventions. 2026;5(4):104454. 

Articles

Cordis’s SELUTION SLR sirolimus drug-eluting balloon received FDA approval for coronary in-stent restenosis based on SELUTION4ISR, a multicenter, single-blind randomized non-inferiority trial versus contemporary care dominated by repeat DES. Twelve-month target lesion failure was similar between strategies, supporting non-inferiority and providing a stent-sparing option. The device uses polymer microspheres with a phospholipid layer to enable controlled sirolimus dosing and sustained vessel-wall contact. Ongoing follow-up will extend to five years, while larger programs explore de novo indications.

Donald Cutlip, MD, discusses the sirolimus balloon’s approval and its role in clinical practice for patients with ISR.