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Following the late-breaking presentation of new data from the global COATING trial comparing two endovascular treatment approaches for unruptured intracranial aneurysms—the p64 MW Hydrophilic Polymer Coating (HPC) Flow Modulation Device (phenox GmbH) plus single antiplatelet therapy (SAPT) versus the uncoated version of the p64 MW device plus dual antiplatelet therapy (DAPT)—Laurent Pierot (Reims University Hospitals, Reims, France) and Omer Eker (Bordeaux University Hospital, Bordeaux, France) outline the study’s strengths, its most important findings, and the impact it could have on the neurovascular space.
With enrolment totalling 171 patients having been completed in November 2024, principal investigator Pierot presented an interim analysis of COATING at this year’s LINNC Paris course (2–4 June, Paris, France), disclosing primary endpoint and safety data from the trial’s 30-day follow-up for the first time.
In conversation with NeuroNews, Pierot notes that the trial met its “quite original” primary endpoint—non-inferiority between patients receiving the p64 MW HPC device (treatment arm) and those receiving the uncoated device (control arm) in terms of core lab-adjudicated diffusion-weighted imaging (DWI) lesions observed within 48 hours of the index procedure. One-month data also revealed statistical parity regarding clinical thromboembolic events and haemorrhagic complications across the study groups.
“Now, we have the proof that the HPC surface modification is working,” Pierot states. “These results show that, when you have a patient in whom DAPT is risky, you can use p64 MW HPC with SAPT, because we know that it has a high safety level.”
“Having a device with a specific coating that prevents platelet aggregation and thromboembolic events, in addition to reducing the [burden] of antiplatelet therapy; it’s quite a revolution in a field in which DAPT has been a dogma when implanting stents intracranially,” Eker adds. “This is the first study that has prospectively randomised patients between the historical approach of a bare stent with DAPT, and a new, coated stent with the potential advantages of SAPT. It’s the first time a private company has dared to do that.”
A primary endpoint that “cannot lie”
A particularly unique aspect of COATING is its choice of primary endpoint. According to Pierot, this is the first major trial in the neurovascular space to use imaging-based DWI lesion occurrences as its main outcome of interest. While Pierot himself admits he would typically prefer to utilise a more clinically focused primary endpoint, rates of symptomatic or clinically significant thromboembolic events in unruptured aneurysm cases are known to be very low, meaning huge study populations would likely be required to uncover any notable differences between two treatment approaches.
Pierot and Eker both posit that this has led to a great deal of heterogeneity in how thromboembolic events— symptomatic or otherwise—are defined and reported within the current literature. DWI lesions, however, offer a more “objective” marker of these types of events.
“DWI lesions are probably the most reliable way to assess thromboembolic events, because most of these events are silent,” Eker explains. “When comparing clinical outcomes, you may be missing some clots that occlude small branches without any [noticeable] consequences. When you target DWI, you’re more objective and reliable. You do not leave room for potentially biased interpretation of variable clinical outcomes. This approach can also be considered more courageous, because there is a very high risk that the device will show a slightly increased rate of thromboembolic events compared to the control arm.”
Eker also notes that, driven by its choice of primary endpoint, COATING is “probably the most robust study conducted to date” in the aneurysm space—on this point, Pierot adds that “DWI cannot lie”. However, he does concede that one small limitation is the fact that it does not provide an indication of thromboembolic events relating exclusively to flow-diverter placement but, rather, the entire procedure, including catheterisation.
The data presented by Pierot at LINNC Paris revealed that the mean number of new, same-territory DWI lesions within 48 hours of the index procedure—measured via magnetic resonance imaging (MRI)—was six in the treatment arm and 5.3 in the control arm. Across the study’s intention-to-treat population, the two groups were therefore deemed statistically similar (p<0.0001) and non-inferiority of the treatment arm was established. In addition, the numbers of patients with observed DWI lesions at 48 hours were comparable between groups: 41 out of 83 (49.4%) in the treatment arm and 49 out of 88 (56.3%) in the control arm.
Pierot and Eker are both advocates of measuring DWI lesions—Pierot has been incorporating the approach into his practice for many years, while Eker says his centre is currently looking to do this more systematically moving forward. Eker also believes that subsequent studies will look at COATING’s design and use it as a benchmark for methodological rigour, stating that—as a primary endpoint or otherwise—DWI lesions are likely to become more ingrained in the future of aneurysm research.
Positive clinical outcomes
Secondary to COATING’s findings on DWI lesions, a number of more traditional clinical endpoints were also reported. Of these, Pierot feels that zero deaths being observed out to 30 days in both study arms is particularly noteworthy, as the vast majority of flow-diverter studies do find some degree of mortality—albeit small. The COATING investigators also concluded that 30-day morbidity—now “relatively precisely defined” as a modified Rankin scale (mRS) score of 3–5, according to Pierot—was “very low” in the treatment arm (4.8%) but also in the control arm (1.4%), and statistically similar between the two. Overall, there was a 3.1% morbimortality rate across the full study population.
“Flow diversion is probably the most efficacious technique for the endovascular treatment of complex and large intracranial aneurysms, at least for the time being, but it was not so safe in the beginning,” Pierot continues. “We had a lot of complications with the first generation of flow diverters. But, now, we are showing that the safety has increased dramatically, and that is one of the interesting results from COATING: the great safety level of flow diversion in general.”
Eker corroborates this point, highlighting the fact that the neurovascular space has progressed from using “very thrombogenic, hard-to-use” flow diverters to today’s “very efficient, safe and easy-to-use” alternatives—with surface-modified devices now demonstrating an ability to help reduce the burden of antiplatelet therapies among aneurysm patients as well.
Additionally, COATING’s interim analyses found a minimal rate of 30-day haemorrhagic complications, with just one postprocedural cerebral haemorrhagic event in the treatment arm (1.2%) compared to two in the control arm (2.3%), and zero intraprocedural cerebral haemorrhagic events in both groups, translating into no statistically significant differences. Here, Pierot notes that the slightly higher numbers seen in the control arm were expected due to the known bleeding risks carried by DAPT, and speculates that a larger study population of 500–600 patients or more may have led to the between-group difference being more pronounced.
What do these results mean?
Discussing the impact these COATING data could have on clinical practice, Pierot states that, in certain subgroups of aneurysm patients—for example, those with an aspirin allergy or heightened risks of haemorrhagic complications—physicians will now be able to confidently implant the p64 MW HPC Flow Modulation Device under SAPT alone. He also believes that confirmation of these findings in the study’s one-year follow-up will be required to instigate the even broader use of the surface-modified device alongside SAPT.
“This shows that, if you use the p64 MW HPC flow diverter with SAPT, the safety is similar to that of the bare p64 MW flow diverter with DAPT,” Pierot comments. “Those are the main results but we still need the one-year follow-up to know if there are any differences in terms of aneurysm occlusion, because being under SAPT only may lead to faster thrombosis of the aneurysm sac.”
Pierot says that one-year follow-up results may provide “important information” on in-stent stenosis too, as the way surface modification influences this outcome is yet to be fully elucidated within a clinical setting. Longer-term data from COATING are expected in the first half of 2026.
“I think it will definitely change things,” Eker adds. “After this study, we expect to see more randomised trials combining a coated device and SAPT. And, in the next 5–10 years, we will probably see SAPT being used more and more with these surface-modified stents, because it is the future—if it does not increase thromboembolic events, and if you can decrease the risk of haemorrhagic complications with SAPT, why wouldn’t you use it?”
And, echoing an earlier point from Pierot on the need for “proper clinical evaluations” that enable endovascular aneurysm treatments to be compared via “precise numbers”, Eker states: “In our field, doing clinical research was difficult for a long time. Between ISAT and this study, there have not been many randomised trials on the haemorrhagic stroke side of things. COATING is a disruptive, innovative study in terms of the assessment of new devices, and I believe it will change the landscape of INR [interventional neuroradiology], leading the way for future studies of devices, techniques and approaches.”
