番茄社区

PARIS -- Advances in bioresorbable scaffold (BRS) technology suggest a new path for innovation: a hybrid approach borrowing from both conventional metallic stents and fully absorbable scaffolds in coronary revascularization.

Here at the EuroPCR meeting, the DynamX "bioadaptor" scaffold had good clinical and imaging results at 12 months reported alongside the promising progress for the more traditional DREAMS 3G magnesium-based BRS.

Both investigational devices were built on lessons learned from the first-generation BRS Absorb, which had been designed to disappear in 1 to 2 years to mitigate stent thrombosis and other adverse events persistent in contemporary drug-eluting stent (DES) technology.

Famously, Absorb showed increased scaffold thrombosis and target lesion failure compared with metallic stents -- and the disappointing results persisted in 5-year data from the ABSORB IV trial, also presented at EuroPCR.

DynamX Bioadaptor Scaffold

With a hybrid design consisting of three metallic strands caged in a bioresorbable coating, the DynamX performed just as well as the Resolute Onyx DES and even showed plaque stabilization and regression in the small BIOADAPTOR RCT trial.

Target lesion failure at 12 months reached 1.8% vs 2.8% (P<0.001 for noninferiority), an endpoint encompassing cardiovascular death, target vessel myocardial infarction (MI), clinically driven target lesion revascularization, and stent thrombosis.

Notably, plaque volume fell 4% in non-calcified lesions and 9% in lipid-containing lesions treated with the bioadaptor scaffold -- whereas plaque grew with the Resolute Onyx, according to Shigeru Saito, MD, of Shonan Kamakura General Hospital in Kanagawa, Japan.

Saito emphasized that DynamX is "not a bioresorbable stent system" as it instead comprises three thin metallic strands overlaid with a poly-lactic-co-glycolic acid (PLGA) bioresorbable topcoat containing sirolimus that elutes over 3 months, and is held together by a poly-L-lactic acid (PLLA) bioresorbable polymer basecoat that resorbs over 6 months. The unlocked helical strands remain for vessel support following neointimal formation and healing.

This is "revolutionary" technology, said EuroPCR course director William Wijns, MD, PhD, of National University of Ireland in Galway. During a press conference, Wijns cited decades of research comparing stents with iterative improvements before the DynamX group finally achieved the "holy grail" of plaque regression.

BIOADAPTOR RCT randomized 445 patients to the DynamX or the Resolute Onyx DES.

With various patient subgroups subject to quantitative coronary angiography, intravascular ultrasound, and optical coherence tomography, imaging showed DynamX's superiority in key secondary imaging endpoints, such as restoration of in-device pulsatility, lower late lumen loss (LLL), and percent diameter stenosis.

The ongoing is aimed at confirming these findings in a larger cohort of 2,400 patients.

DREAMS 3G Resorbable Magnesium Scaffold

Meanwhile, the thinner DREAMS 3G showed improvement from its predecessor in terms of re-stenosis at 12 months, when the BRS is expected to disappear.

In the , in-scaffold LLL was 0.24 mm with DREAMS 3G, compared with the historical 0.39 mm seen with DREAMS 2G in the BIOSOLVE-II study. Similarly, in-segment LLL favored the 3G at 0.10 mm vs 0.25 mm, according to Michael Haude, MD, PhD, of Rheinland Klinikum Neuss-Lukaskrankenhaus in Germany.

Intravascular imaging showed good strut apposition after index procedure and lumen preservation, Haude said. Furthermore, the 12-month target lesion failure rate was 2.6% -- essentially all clinically-driven target lesion failure with zero scaffold thrombosis.

The third-generation DREAMS 3G contains new proprietary magnesium alloy backbone and sirolimus-PLLA coating. Strut thickness has been reduced to as low as 99 μm, down from the 150 μm thickness of the DREAMS 2G.

BIOMAG-1, a first-in-human trial of 116 people with de novo coronary artery lesions, paves the way for a larger randomized trial comparing DREAMS 3G against contemporary third-generation DES. Soon to begin recruitment is the with over 1,700 patients randomized to the DREAMS 3G or the Xience DES.

"We're marching toward a real bioresorbable stent, getting closer to that, but ... these are early steps," commented session panelist Upendra Kaul, MD, of Batra Hospital & Medical Research Centre in New Delhi.

Lessons From First-Gen Absorb

Early days with the Absorb device placed the blame of poor device performance on suboptimal implanter technique, but even getting operators on board with a strict protocol was not enough to give the BRS a win in the ABSORB IV trial.

Compared with the conventional metallic Xience stent, Absorb was associated with excess target lesion failure at 5 years (17.5% vs 14.5%, HR 1.24, 95% CI 1.02-1.52), driven by target vessel MI and ischemia-driven target lesion revascularization. In particular, the differences were limited to the first 3 years (13.7% vs 10.5%) on landmark analysis, reported Gregg Stone, MD, of the Mount Sinai Health System in New York City.

At 5 years, stent thrombosis rates were no longer statistically different between devices (1.7% vs 1.1%, HR 1.65, 95% CI 0.82-3.29), following an early difference detectable at 3 years (1.4% vs 0.6%, HR 2.47, 95% CI 1.02-5.96).

ABSORB IV was designed to give the first-generation PLLA-based everolimus-eluting BRS the greatest edge possible, testing the device in an expanded population of 2,604 people with improved operator technique compared with earlier trials. Yet the study's confirmation of excess thrombosis was part of the reason why FDA cautioned against using Absorb and the device was ultimately .

"The [present] results come as no great surprise and are broadly consistent with what we've seen in other studies," commented session discussant Róisín Colleran, MBBCh, of Mater Private Hospital in Dublin. While it was hoped that an optimized implanter technique in larger vessels, including MI patients, might still improve outcomes in the long run, "unfortunately it wasn't the case in this study," she said.

During the panel discussion, Stephan Windecker, MD, of Bern University Hospital in Inselspital, Switzerland, nevertheless congratulated Stone on the 5-year report as it shows "we can learn a lot from failures."