12-Month EXCITE ISR Data Presented at New Cardiovascular Horizons, Showing Favorable Results for Laser in In-Stent Restenosis

May 27, 2015—Twelve-month data from the Excimer Laser Randomized Controlled Study for Treatment of Femoropopliteal In-Stent Restenosis (EXCITE ISR) were presented at the New Cardiovascular Horizons (NCVH) meeting in New Orleans, Louisiana. The data, shared with the NCVH audience by Craig Walker, MD, showed that laser atherectomy plus percutaneous transluminal angioplasty (PTA) was safer and more effective than PTA alone for treating femoropopliteal in-stent restenosis (ISR), demonstrating continued durability at 12-months. Dr. Walker is an EXCITE ISR principal investigator and the Chairman of NCVH.

Dr. Walker summarized EXCITE ISR as a randomized, controlled trial conducted in the United States that showed highly statistically significant improvements in both safety and efficacy. The trial's primary efficacy endpoint was freedom from target lesion revascularization through 6 months, and the primary safety endpoint was freedom from major adverse events (MAE) at 30 days. MAE included all-cause mortality, major amputation in the target limb, or target lesion revascularization. The 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. Spectranetics Corporation previously announced that the EXCITE ISR trial had achieved highly significant statistical superiority in both safety and efficacy among 252 patients, and in 2014, the US Food and Drug Administration granted 510(k) clearance for peripheral laser atherectomy in the treatment of ISR.

In the trial, the cohort treated with the company's Turbo-Tandem device plus PTA showed significantly less residual stenosis and need for bailout stenting as compared to the cohort in which ISR was treated with PTA alone. The procedural success rate using Turbo-Tandem plus PTA was 92.9% versus 81.7% with PTA alone (P = .01). The primary safety endpoint was 5.4% for laser plus PTA versus 20.8% with PTA alone (P < .001). The primary efficacy endpoint was 78.3% versus 58.9% with PTA alone (P = .002). Additionally, laser atherectomy with adjunctive PTA was associated with a 43% reduction in target lesion revascularization through 12 months (hazard ratio, 0.57; 95% confidence interval, 0.38–0.84; P = .005).

Speaking with Endovascular Today after the data presentation, Dr. Walker emphasized that although the trial was randomized, the treatment arm had demographics that may have been predisposed to poorer outcomes, yet this arm saw better results.

"There were highly statistically significant differences, with more TASC C and D lesions in the treatment arm, which would typically impart a worse prognosis,"  explained Dr. Walker. "There were slightly longer lesions in the laser group, though not statistically significant, and there were more stent fractures and more calcium in the index procedures. So, we might have anticipated, based on historical outcomes, that the laser group would have fared much worse, yet they fared better—they were safer and more efficacious."

As to how he feels the EXCITE ISR trial and its data might be applied in current practices, Dr. Walker said that in many cases it is desirable to "leave nothing behind," but some patients still require stent placement. And, while it is important to emphasize that most stented lesions stay open, ISR remains what he calls a "monstrously huge problem."

"ISR is a problem that, even if no stents were placed from this point on, will be with us for a long time because many stents have been placed over the years. In-stent restenosis is not just a phenomenon that occurs at 1 month, 6 months, or 12 months—it may occur throughout the lifetime of that patient," Dr. Walker continued. "However, there will always, in my opinion, be cases that require some form of stenting. You can do angioplasty, atherectomy, and follow that with a drug-coated balloon, but if you don’t have a good channel, you’re unlikely to have a good long-term result. So, you have to do something to scaffold it to keep it open. I don’t see stenting going away. I think it is a very useful treatment modality."

Dr. Walker went on to describe the process of ISR formation and why it is an excimer laser-based therapy produces better results than PTA alone. Because ISR typically manifests as intimal ingrowth within a fully expanded self-expanding stent, at times forming a total occlusion with thrombus present, the capabilities of angioplasty alone will always be limited, he said. "Unlike in a native vessel, you can't further stretch it out, because the stent displacement will forever limit positive remodeling. You can acutely stretch it, but there will simply be a rubberband effect. The second thing that happens, and this has been shown in coronary in-stent restenosis data in the past, is that you acutely dehydrate the intimal hyperplasia [when treating it with PTA alone]. You have a channel that looks OK, but if you simply wait 20, 30, or 40 minutes, it rehydrates, and when it does, the lesion is back. So, I think it’s important in some way, shape, or form, to remove some of that tissue if you wish to get a good result."

Summarizing his thoughts on the outcomes from EXCITE ISR, Dr. Walker said, "I’m not surprised at all that photoablation, which actually removes the offending material, would result in better outcomes, that it would be both safer and more efficacious."