DESSOLVE III: MiStent Holds Up Well Against Xience at 12 Months, Hints at Potential Longer-Term Benefit
The MiStent bioresorbable polymer dissolves within 3 months but sirolimus microcrystals embedded in the wall stick around much longer.
PARIS, France—A new stent coated with a crystalline form of sirolimus—a device designed to promote extended drug elution long after the bioresorbable polymer has vanished—fared just as well as a workhorse drug-eluting stent in a head-to-head trial presented today at EuroPCR 2017.
In DESSOLVE III, an all-comers study that included patients from 20 clinical sites in four European countries, there was no significant difference in the risk of device-oriented clinical events, a composite endpoint that included cardiac death, target-vessel MI, and clinically-indicated TLR, among patients who received the MiStent sirolimus-eluting stent (Stentys) and those treated with the Xience everolimus-eluting stent (Abbott Vascular).
“The rationale is that the durable polymers, the polymers that are coated on the stent and are present in the vessel wall for a longer period of time, may induce inflammation and eventually lead to intimal growth, restenosis, and new atherosclerosis,” said lead investigator Robbert de Winter, MD (Academic Medical Center, Amsterdam, the Netherlands). With MiStent and its bioresorbable polymer and prolonged drug elution, “in theory, you would expect that any inflammatory response from the coating will be counteracted by the drug.”
The MiStent device’s absorbable poly-L-lactic acid (PLLA) polymer degrades within 3 months and is coated with a microcrystalline form of sirolimus that embeds directly into the vessel wall. In this way, there is sustained drug elution—up to 9 months—long after the polymer has broken down and been absorbed by the body. The cobalt-chromium MiStent is also a thin-strut device, with struts just 64 µm thick.
“We’ve actually got three things going on,” said de Winter. “We have a thin-strut platform, a fully bioresorbable PLLA polymer which disappears at 3 months, and a drug that is present in the vessel wall for 9 months. When compared with other stents available at the moment, usually the polymer coating, if it’s a bioresorbable coating, then it’s around for 3, 6, or 9 months, but the drug will be gone while the polymer is still there.”
Signal at 12 Months, But Longer Follow-Up Needed
DESSOLVE III included 1,398 patients; about 60% had acute coronary syndrome as the indication for PCI. Investigators also included patients with diabetes, left-main disease, restenotic lesions, and saphenous vein grafts. All patients received dual antiplatelet therapy in accordance with clinical guidelines, that being 6 months for patients with stable angina and 12 months for those with acute coronary syndrome.
At 1 year, there was no statistically significant difference in the rate of device-oriented clinical events (5.8% with MiStent vs 6.5% with Xience; P < 0.001 for noninferiority). Similarly, there were no differences in any of the individual components of the primary endpoint. There was a trend toward a lower risk of clinically-indicated TLR with the novel device, but the difference was not statistically significant (2.6% vs 3.8%; P = 0.22).
“We see a signal at 12 months,” said de Winter, referring to the TLR rate. “The trial is planned for 3 years so we’d expect to see this difference panning out between 1 and 3 years.”
Speaking during the late-breaking clinical trials session, Chaim Lotan, MD (Hadassah Medical Center, Jerusalem, Israel), said it remains difficult to show a significant difference between stents given the low rates of major adverse cardiovascular outcomes with the latest-generation devices. Chaim said the signal of a lower risk of restenosis with MiStent is promising, which might be attributable to the disappearing polymer, prolonged drug elution, or the thinner struts. Regardless of the reason, Lotan was impressed with the results.
“Definitely, it’s another good stent on the shelf,” said Lotan.
Investigators did not mandate angiographic follow-up as part of the trial, but there will be an optical coherence tomography (OCT) substudy presented later in the meeting. “If you look at late lumen loss with Xience, there is a slow accrual over time,” de Winter told TCTMD. “With the OCT study, there is less late lumen loss in the MiStent arm compared with Xience.”
There is also angiographic evidence from the DESSOLVE I and II studies that late lumen loss “is flat after 6 months in contrast with the drug-eluting stents, which have an accrual of late neointimal growth after 6 months to 1 year,” he said.
Robert Byrne, MD (Deutsches Herzzentrum, Munich, Germany), said one of the first comments that emerges during noninferiority studies is, “Noninferior—so what?” The MiStent device is a “potentially interesting device,” though, particularly given its noninferiority to the high-performance Xience stent, and offers the possibility of later benefit, particularly in terms of reducing late catch-up and subsequent events, he added.
As the lead author of the 2015 European Society of Cardiology/European Association of Percutaneous Cardiovascular Interventions (ESC/EAPCI) task force for the evaluation of coronary stents in Europe, Byrne said the MiStent development program “checks a number of boxes.” There was a successful first-in-man study, a successful angiographic study with limited patients, and now DESSOLVE III with clinical endpoints.
“This is what we want to see in the regulatory space for the stents that we use to treat our patients day in and day out,” said Byrne. In terms of limitations, he questioned the 4% margin of noninferiority used in the trial, which he said was quite generous.
Photo Credit: Stentys (adapted from: http://www.stentys.com/62/3/articles/mistent.html)
De Winter R. DESSOLVE III: a randomized comparison of Xience vs MiStent, a novel ES that embeds sirolimus microcrystals in the vessel wall. Presented at: EuroPCR 2017. May 16, 2017. Paris, France.
- De Winter reports receiving research/grant support from OrbusNeich Medical, Abbott Vascular, AstraZeneca, Stentys, and Tryton.