FUTURE II: A Good ‘First Step’ for Thinner-Strut Bioresorbable Scaffold

A new bioresorbable scaffold (Firesorb, MicroPort Medical), one with much thinner struts compared with first-generation “dissolving” devices, has shown some early promise in a study of patients with relatively simple coronary artery lesions.

Presenting the results of FUTURE II as a late-breaking clinical trial at EuroPCR, Bo Xu, MBBS (National Clinical Research Center for Cardiovascular Disease/Peking Union Medical College, Beijing, China), reported that in this trial, which included operators adhering to a dedicated implantation technique, the bioresorbable scaffold was noninferior to a cobalt-chromium everolimus-eluting stent (Xience; Abbott Vascular) for the primary endpoint of in-segment late lumen loss.  

While FUTURE II is a small study looking solely at angiographic outcomes, Xu said he remains optimistic about the technology. “I think, although this is a very small sized study with angiographic outcomes is comparing a new device with a drug-eluting stent, this is always the first step,” he commented. “After the first-in-man randomized study, now we expanded the indication to test this new device in larger studies. However, we believe it [represents] an opportunity.”

To TCTMD, Xu said that although the use of optimal implantation techniques for bioresorbable scaffolds might be part of the reason they achieved good results, he predicts the thinner-strut device on its own will offer advantages over the older scaffolds. “For example, if you look carefully at the OCT [optical coherence tomography] immediately after implantation, you can see the strut can be embedded into the vessel wall,” he said. “It’s much better than the first-generation [devices].”

Gregg Stone, MD (Icahn School of Medicine at Mount Sinai, New York, NY), who oversaw the ABSORB global research program with the Absorb bioresorbable vascular scaffold (BVS; Abbott Vascular), said the results of Firesorb look good at present, noting that the thinner-strut device should theoretically lead to more-rapid endothelialization and better embedment in the vessel wall. Nonetheless, there is more work to be done in this area. 

“There still needs to be optimization of all [poly-L-lactic acid]-based scaffolds,” said Stone. “I think the outcomes can continue to be improved if the struts are continued to be made thinner. At 100 to 125 µg, the Firesorb stent struts are still thicker than contemporary drug-eluting stents. I think this is a step in the right direction, but reducing strut thickness and improving the mechanical expansion properties will continue to improve outcomes for bioresorbable scaffolds.”

There are other commercially available bioresorbable scaffolds available in Europe and Asia, but the rise and fall of the Absorb device is perhaps the best known. Following 1-year data from ABSORB III, where the scaffold was shown to be noninferior to Xience, Absorb was approved in the United States. However, longer follow-up revealed safety issues. Absorb was associated with an approximate twofold increased risk of device-oriented adverse events, including target-vessel MI and late scaffold thrombosis, compared with Xience. Other negative studies and meta-analyses followed and Absorb was eventually discontinued.

Absorb was a thick-strut scaffold at more than 150 µg, which the FUTURE II investigators say may have led to more turbulent flow, delayed reendothelization, and unfavorable dismantling as it was being absorbed. In contrast, the Firesorb scaffold has struts that range from 100 to 125 µg depending on the size of the scaffold. In a discussion at EuroPCR, Xu said the strut thickness is personalized to the stent size, with the 2.5- and 2.75-mm scaffolds having struts 100 µg thick while the other longer lengths are 125 µg. “We’re trying to decrease the thickness of the device while maintaining the radial force,” he said.  

What’s Old Is New in FUTURE II

FUTURE II was a prospective, multicenter, randomized trial that included 430 patients with myocardial ischemia undergoing elective PCI in one or two epicardial coronary vessels. The lesions were 25 mm or less in length and had a diameter ranging from 2.5 to 4.0 mm. The primary endpoint was angiographic in-segment late lumen loss at 1 year, and the key secondary endpoint included the proportion of patients with covered struts in patients who underwent OCT imaging at 1 year (n = 79). Angiographic follow-up was available in 87.5% of patients, and 96% of patients remained on dual antiplatelet therapy for 1 year.

Overall, the study met its primary endpoint, with investigators observing no significant difference in patient-level in-segment late loss between Firesorb and Xience

FUTURE II: Mean In-Segment Late Loss

As for the secondary OCT endpoint, which was available in 66 patients, Firesorb was noninferior to Xience in terms of the proportion of strut coverage at 1 year. The Firesorb device also had a lower incidence of incomplete strut apposition. Clinical outcomes did not differ between the two devices, with investigators reporting no difference in the rate of target lesion failure (1.9% with Firesorb vs 3.3% with Xience; P = 0.37) and no difference in the patient-oriented composite endpoint of all-cause mortality, all MI, or any revascularization. There were no cases of definite/probable device thrombosis in either treatment arm.

“The trial wasn’t powered for clinical events, although no concerns of adverse clinical outcomes were observed,” commented Stone. “The trial was powered for follow-up late loss at 1 year and that was similar between the two arms. Basically, it’s consistent with the scaffold being a potent antiproliferative drug-eluting device.”

In terms of the procedure, FUTURE II operators were strongly recommended to adhere to PSP—predilatation, appropriate sizing, and postdilatation—a strategy proposed and later adopted by the ABSORB investigators. Rates of predilatation and postdilatation were 100% and 96%, respectively, with Firesorb.

Stone said that the results of FUTURE II were impressive in that they were achieved without the use of IVUS. Its routine use, Stone believes, can continue to further improve outcomes. As stent struts get thinner and the radial force is maintained or increased, the absolute meticulous technique required with bioresorbable scaffolds might become less critical, but “for the foreseeable future, we have to pay much more attention to, one, avoiding very small vessels and, two, optimal lesion preparation and high-pressure postdilatation with oversized, noncompliant balloons to achieve the safety we want to see compared with the metallic drug-eluting stents,” said Stone.

In a discussion following the late-breaking trial Martin Leon, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), said Firesorb is clearly an advancement over Absorb given its thinner struts, excellent geometry, abluminal coating with sirolimus, and 3-year dissolution time. “We don’t want to get ahead of ourselves,” he said. “I think our [FUTURE II] colleagues were really smart to do a careful randomized trial in noncomplex patients, in noncomplex lesions, with good follow-up at 1 year. It gives us a good framework to go forward.”

FUTURE II, he said, gives the research community encouragement to move forward, and to hopefully regain momentum. “This is just the beginning,” he stressed. “We certainly have to look at late follow-up. Many of the safety consequences occurred late with [Absorb].” 

Xu agreed that they took a cautious approach with FUTURE II and included patients with larger vessels, noting the reference diameter was 2.9 mm. For the next steps, the single-arm FUTURE III is already ongoing; the primary endpoint in that trial is TLF among 1,200 patients treated with Firesorb. He said they plan to study patients in FUTURE II for at least 5 years.

William Wijns, MD, PhD (Lambe Institute for Translational Medicine, National University of Ireland Galway), who moderated the press conference where Xu first presented the results, told TCTMD there’s still a future for bioresorbable scaffolds. “The short answer is yes,” said Wijns when asked. “Colleagues who have good experience with [the Absorb BVS] still miss it in a number of indications—at least that’s the message we’re getting from the community.”