Twelve-month data from the EXCITE ISR clinical trial were presented by Craig Walker, MD, at the 2015 New Cardiovascular Horizons (NCVH) meeting in New Orleans. Results of the landmark study show that Spectranetics’ Turbo-Tandem and Turbo-Elite laser atherectomy devices used with balloon angioplasty are safer and more effective than angioplasty alone for treating femoropopliteal in-stent restenosis (ISR), demonstrating continued durability in 12-month results.
The EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis (EXCITE ISR) is a first-of-its-kind large multicenter prospective randomized trial conducted for the treatment of femoropopliteal ISR. The EXCITE ISR trial was designed to enroll a maximum of 318 subjects at up to 40 sites, randomized 2:1 treatment to control with predetermined statistical analyses at 200, 250, and 300 enrolled patients. Critical data findings include significantly less residual stenosis and need for bail-out stenting, improved success rate, and a significantly reduced major adverse event rate. In July 2014, Spectranetics received FDA 510(k) clearance for Turbo-Tandem and Turbo-Elite to treat ISR.
Dr. Walker, an interventional cardiologist with Cardiovascular Institute of the South and a clinical professor of medicine at Tulane University and LSU medical schools, served as an EXCITE ISR co-principal investigator. Vascular Disease Management talked with Dr. Walker about the 12-month data.
Q: Could you share an overview of the study design?
A: In the EXCITE trial, there were 252 patients. I must state that this trial was actually stopped prematurely because it had already reached statistical endpoints. These patients were randomized in a 2:1 fashion to receive either laser followed by balloon angioplasty or balloon angioplasty alone. This is an important study because up until this study there were no approved therapies for the treatment of superficial femoral artery in-stent restenosis, which is a huge problem. As more and more stents are being placed around the world we are seeing more and more in-stent restenosis, and this is a particularly difficult treatment. The reason that it’s difficult is that the stents often thrombose totally, and in treating these patients there is a risk of embolization. In addition, you may not get normal results because even though we can acutely stretch the stent and dehydrate the intimal hyperplasia, you get elastic recoil, and you get rehydration of the intimal hyperplasia resulting in restenosis, and this is incredibly common with balloon angioplasty alone.
Q: Why do you think we get such a benefit from using the laser as opposed to not using the laser?
A: Excimer laser actually removes the intimal hyperplasia and thrombus, when present, in total occlusion by a process known as photoablation. It actually converts it into molecular debris. Typically this results in a channel that’s been cleaned out rather than simply stretched.
Q: What was the most exciting finding from the 12-month data in your opinion?
A: The initial data were incredibly encouraging in that laser showed that it was not only more efficacious than balloon alone but it was safer than balloon alone and these were highly statistically significant endpoints. At a year there was a 43% relative risk reduction in the need for revascularization in the laser cohort and this group was statistically significantly more difficult to treat, the lesions were longer, there were more fractures, and there was a statistically different amount of patients with TASC C and D lesions, so we would’ve expected much worse results based on the results of randomization and yet we had substantially better results both in terms of safety and efficacy.
Q: How do you think the laser will fit into clinical decision-making for interventionalists in the future?
A: I believe, based on these data, that at present interventionalists must have lasers to treat in-stent restenosis. I think it’s going to become part of the treatment paradigm. I don’t know if we need it for very, very short lesions that are just stenotic but certainly we will in Tosaka class II or III lesions where stenosis is very high. Some studies show as high as 80% within a few months in very long total occlusions. I think that this is going to be a therapy that interventionalists must have to lessen risk and improve outcomes.
Q: Is there anything else you would like to add?
A: This trial was the first randomized controlled trial thus far that showed a benefit of atherectomy that’s very clear beyond a shadow of a doubt. It was a randomized controlled trial. The other thing that was remarkable about this trial was that the lesions treated were very long. The average lesion that was treated by laser plus balloon in this report was 19 cm. That’s far longer than most reported treatment lengths. So I’m very encouraged by this. I think that this means that there is a role for removing “gunk” that is built up inside the vessel. I think that it means that removing this gunk might indeed result in a better channel, and might indeed lessen the risk of knocking some of the stuff off downstream. It also gives us great hope for treating very long lesions.
I really believe that with these data every interventionalist treating patients with in-stent restenosis really needs to learn and understand laser atherectomy technology. The data clearly show that it is safer than using a balloon alone, but there are questions remaining. How will this be coupled with things such as drug-eluting therapies? How will it be coupled with a complementary stent? I don’t know these answers at this point, but this is certainly a great starting point clearly showing that we can effectively treat ISR and now we have something that is FDA approved for his treatment. Up until this time we really couldn’t talk on label about much for the treatment of ISR.
Highlights From Excite ISR Results
- Treatment using Turbo-Tandem resulted in significantly less residual stenosis and need for bail-out stenting.
- 92.9% procedural success rate using Turbo- Tandem with balloon angioplasty vs 81.7% with balloon angioplasty alone (P<.01).
- Primary safety endpoint, major adverse events (MAEs) rates at 30 days 5.4% vs 20.8% with balloon angioplasty alone (P<.001).
- Primary efficacy endpoint freedom from tar- get lesion revascularization through 6 months was 78.3% vs 58.9% with balloon angioplasty alone (P=.002)
- Excimer laser atherectomy with adjunctive balloon angioplasty was associated with a 43% reduction in target lesion revasculariza- tion through 12 months (Hazard Ratio 0.57; 95% CI 0.38-0.84; P=.005).
Craig Walker, MD, is an interventional cardiologist with cardiovascular Institute of the South and a clinical professor of medicine at Tulane University and LSU Medical schools in Louisiana. He is the EXCITE ISR co-principal investigator.