Daring to Dream: New BRS Data Hint at Low MACE Rates at 2 and 3 Years

PARIS, France—In a EuroPCR 2019 session devoted to bioresorbable vascular scaffolds, including the now abandoned Absorb device (Abbott Vascular), investigators dared to raise their hopes on the basis of midterm data from a new scaffold that did not show a safety signal in a small number of patients.

In the MeRes-1 study testing a next-generation bioresorbable scaffold (MeRes100; Meril Life Sciences), a device with thinner struts compared with Absorb, the 3-year data look relatively good, with investigators reporting a major adverse cardiovascular event rate of just 1.87%. In 107 patients treated with the sirolimus-eluting bioresorbable scaffold, two patients underwent revascularization of the target lesion.

Moreover, in the MeRes-1 Extend study, a similar trial with 62 patients, the 2-year MACE rate was 1.61%, with just one case of ischemia-driven TLR.

Importantly, there were no reported cases of scaffold thrombosis in the MeRes-1 and MeRes-1 Extend studies.

Praveen Chandra, MD (Medanta – The Medicity, Gurgaon, India), who presented the results of MeRes-1 following several registry presentations highlighting a continued risk of scaffold thrombosis with Absorb, joked that the EuroPCR audience is unlikely to be optimistic about the technology. Nonetheless, the next-generation MeRes100 bioresorbable scaffold does offer “some light and some hope,” said Chandra.

The MeRes100 scaffold is already approved in India and received CE Mark approval from European regulators just a few days ago.

Franz-Josef Neumann, MD (University Heart Center Freiburg, Bad Krozingen, Germany), offered a sober take on the new results, stating the studies provide evidence of initial safety in patients with relatively straightforward lesions. What’s lacking is evidence for long-term efficacy and safety compared with conventional drug-eluting stents.

“We need more data,” said Neumann. “I don’t think it’s fit for widespread clinical use. That was the mistake we made with Absorb. It went into widespread use before we really had enough safety and efficacy data. In fact, we need to show an advantage [with bioresorbable scaffolds] between 5 and 10 years where we would expect it, but we still don’t have that.”

To TCTMD, Nick West, MD (Royal Papworth Hospital, Cambridge, England), said that for believers in bioresorbable technology, further device iteration is critical.

“Having a thin-strut device, we all believe will be beneficial,” he said. “Whether it will be beneficial remains to be tested thoroughly. These early data are encouraging, but we need larger studies. We need randomized studies with longer follow-up before we can really embrace large-scale uptake no matter the fact it’s been approved in India and received CE Mark. I think for those of us who believe in these technologies, we’re going to want to wait.”

Thinner Struts Compared With Absorb

The MeRes100 bioresorbable scaffold is a second-generation device with hybrid geometry and a strut thickness of 100 µm, which is thinner than the Absorb struts (150 µm).

MeRes-1 included patients 18 to 65 years with a lesion length 20 mm or less and a reference vessel diameter ranging from 2.75 to 3.50 mm. Roughly 25% of patients had diabetes and 34% had a previous MI. In terms of clinical presentation, 52% of patients had stable angina, 34% unstable angina, and 14% silent ischemia. Dual antiplatelet therapy was planned for 1 year, although some physicians prolonged its use in light of the ABSORB studies, according to investigators.    

Chandra said their cumulative MACE rate, a combined endpoint that includes cardiac death, MI, and ischemia-driven TLR, is better at 3 years than data reported from the ABSORB Cohort B trial. In that study of 101 patients, the MACE rate was 10% at 3 years compared a rate of 1.87% in MeRes-1. Imaging was performed in a small number of patients, but optical coherence tomography (OCT) data showed that the mean strut area was in decline at 2 years and 99% of struts were covered. Additionally, late lumen loss measured by quantitative angiography at 2 years was low, although it did increase from 6 months.  

The MeRes-1 Extend study included nearly identical patients, although Extend investigators included only patients with A/B1 lesions, and their clinical results were similar. In 24 patients who underwent OCT imaging, there was sustained flow from baseline and near complete strut coverage at 6-month follow-up. Late lumen loss at 6 months was 0.18 mm.

Regarding the “zero incidence” of scaffold thrombosis at 2 and 3 years in these trials, Neumann said he remains skeptical of such perfect numbers, noting this is just a small mechanistic study that deserves further follow-up. Alexandre Abizaid, MD (Dante Pazzanese Institute of Cardiology, Sāo Paulo, Brazil), agreed, and said that with the CE Mark approval, investigators will have a little greater freedom in designing future studies with a more scrutinized control group. “I think it’s warranted to have randomized trials,” he said.

For West, however, comparing early results from the MeRes-1 studies against data from the ABSORB studies is unfair. “Any new device that comes through now, it’s going to be very difficult to tease out whether it’s the device that’s better or whether it’s physician behavior. We all learned from the Absorb Wars, if you like, about predilatation, sizing, postdilatation, and possibly the use of imaging and antiplatelet therapy. Anything that comes now will have the benefit of all that.”

Addressing Bulky Struts of First-Generation Scaffolds

During the EuroPCR presentations, investigators and panelists acknowledged that the early data with Absorb also looked quite good. The early shine came off when several studies with longer follow-up revealed a significantly increased risk of target lesion failure and device thrombosis. While some speculated that these risks could be mitigated with good implanting techniques, the so-called PSP protocol (predilatation, appropriate sizing, and high-pressure postdilatation), several studies, including data from the AIDA trial, suggested this was not the case.

“Up to 3 years, the problems were persisting,” said Chandra, referring to heightened risk of thrombotic events with Absorb. “We still don’t know the culprit. Was it lesion selection, dilatation, sizing, or is it the device? We kept changing our techniques, but we also changed the device.”

The low MACE rate and zero incidence of device thrombosis are promising, he added, stating that he’s optimistic one of the drivers of scaffold thrombosis—strut thickness—has been identified. “I’m not saying it’s going to be like this forever, but it certainly gives us a lot of optimism, or at least an idea, that one of the culprits has been caught.”

Abizaid, who presented the results of MeRes-1 Extend, said Absorb’s thick struts made the device bulkier and potentially more thrombogenic. In addition, there was a learning curve and its optimal use was dependent on IVUS and OCT imaging. Overlapping scaffolds were problematic, as was use in small diameter vessels, said Abizaid. 

“Our dream is to have a truly next-generation device that should overcome some of these limitations,” he said. “But it’s very hard to have an ideal device that will have all of these attributes, but some of them we really should see in next-generation devices, including reduced strut thickness. I think this will be mandatory if this technology is to prevail.”

In early 2017, the European Society of Cardiology and European Association of Percutaneous Cardiovascular Interventions issued updated guidance on the use of bioresorbable scaffolds and recommended physicians not use any of the commercially available devices over drug-eluting stents. With its CE Mark, MeRes100 joins DESolve (Elixir Medical), Arterial Remodeling Technologies bioresorbable scaffold (ART), Fantom (Reva Medical), and Magmaris (Biotronik) on the European market. Abbott Vascular halted sales of Absorb in September 2017.