Slimmest Stent to Date Looks Promising in Small Study

PARIS, France—Some of the smallest vessels in the coronary tree now have their own stent—provided regulators are persuaded by data from the RESOLUTE ONYX 2.0 mm stent study, which was presented yesterday here at EuroPCR 2017 and showed low rates of target lesion failure (TLF) at 1 year.

“This dedicated size of Resolute Onyx allows for the successful treatment of lesions involving extremely small vessels, thereby fulfilling an important unmet clinical need,” said Matthew Price, MD (Scripps Clinic, La Jolla, CA).

The single-arm study, which enrolled 101 patients at 20 sites in the United States and Japan, was conducted to support US approval of the Resolute Onyx stent. The smallest size of the device—with a strut thickness of 81 μm (compared with 91 μm for its predecessor, the Resolute Integrity)—is 2 mm in diameter. If approved, it would be the smallest stent on the market, according to the manufacturer, Medtronic.

At issue, however, is whether diseased vessels with a reference diameter smaller than 2.25 mm actually need stenting—that question has never been studied in a randomized trial. Instead, the current trial was designed to beat a historical performance goal of 19%, set at twice the expected TLF rate of 9.4%, based on estimates from the weighted average of rates observed with 2.25-mm DES and “the known association between smaller RVD and increased event rates,” according to the small print in Price’s slides. To TCTMD, Price noted that studies of 2.25-mm stents had performance goals set at about 21% to 22%.

Clinically significant disease suitable for stenting is also relatively rare in vessels this size, Price admitted to TCTMD. “It’s not terribly common,” he acknowledged, “but there’s a clear number of patients with very-small-diameter vessels that you walk away from and say, well, that’s just too small to stent, or you put in a 2.25-mm stent and underexpand it, or you do cosmetic angioplasty with a 2.0 balloon, very gently, and hope you don’t cause a dissection.”

Thinking Small

To be enrolled in the current study, patients had to have de novo lesions < 27 mm in length with a reference vessel diameter of 2.0 mm or greater, but less than 2.25 mm, by visual estimation. Importantly, all patients had to have stable or unstable angina and fractional flow reserve (FFR) confirmation of ischemia “to really make sure that we were not just putting small stents in small arteries that were not clearly clinically meaningful,” Price said. A separate myocardial perfusion substudy will be reported at a future date.

At 1-year, TLF was 5.0%, significantly lower than the 19% performance goal (P < 0.001). TLR was rare, occurring in 2% at 1 year. There were no stent thromboses in the study and three target-vessel MIs. An angiographic substudy conducted in 26 patients (after their 1-year clinical follow-up) showed in-stent late lumen loss of 0.26 mm and a binary stenosis rate of 12% (20% in-segment).

That late loss is “consistent” with prior-generation stent studies, Price said, although he acknowledged that the binary restenosis rates were higher than ideal. “I think that’s due to the lack of head room,” he said. “If you have a small vessel and a small stent, even a small amount of late loss will give you larger percent diameter stenosis over time. So what this tells me is that this is a very good stent, but we can’t forget to treat the patient aggressively [to] stop the progression of small vessel disease in addition to treating obstructive lesions with a small stent.”

Session co-chair David Holmes, MD (Mayo Clinic, Rochester, MN), questioned Price about postprocedural imaging. “Is it pretty important in these patients with small vessels that you have the stent just perfectly done and opposed? Because the room for error is pretty small.”

Price responded saying that “intuitively you’d think that you might have stent underexpansion,” but in fact IVUS or optical coherence tomography were not mandated in the study and were not widely used. “Despite that,” he said, “you had no stent thromboses and you had only 2% TLR . . . . We’ll get continuing data from postapproval studies, assuming this is approved, which will give us an understanding of long-term follow-up, but for a study of 100 patients, 0% stent thrombosis, and pretty good-looking clinical outcomes, I think we can rest assured that this will be a pretty good tool in our armamentarium for very small vessels.”

Gregg Stone, MD (NewYork-Presbyterian/Columbia University Medical Center, New York, NY), commenting on the study for TCTMD, was not entirely convinced, pointing out that there is no evidence to support a strategy of stenting over plain-old balloon angioplasty in these small lesions. “I think in general most 2-mm vessels that need treatment can be treated with 2.25-mm stents, which have been available for some time,” Stone said. There will be “an occasional vessel” that is too small for a 2.25-mm stent. “But I think we do fairly well with balloons in these vessels.”

Price, however, said the best strategy for these lesions is unlikely to be studied “and might even be unethical,” given the results he reported yesterday. “The issue is that there’s nothing really to compare it to and I think that’s part of the reason why it was the FDA wanted to make sure we were putting a stent in lesions that needed it, which is why we had sites do FFR.”

Asked to estimate the proportion of lesions that might benefit from this small stent, if approved, Price said: “I would say, offhand, maybe 5% could use a 2.0 stent. It’s a small number but still an important number.”