Surface-modified flow diverters for intracranial aneurysms: narrative review on mechanisms, evidence, and clinical implications

Background and Objective: Flow diverters (FDs) have significantly advanced the treatment of intracranial aneurysms, especially for the large, wide-necked, or surgically inaccessible ones. However, the high metallic footprint of traditional FDs poses a substantial thrombogenic risk, necessitating prolonged dual antiplatelet therapy (DAPT). This also makes flow diversion a high-risk treatment for acutely ruptured aneurysms. Developments in FD surface modifications aim to mitigate thrombogenicity while promoting endothelialization, with the potential to enable safe treatment under single antiplatelet therapy (SAPT). This review consolidates the molecular mechanisms, preclinical findings, and clinical outcomes of currently available coated/surface-modified FDs to serve as a practical guide for neurointerventionalists. Methods: A literature review was performed using databases (PubMed, Embase, MEDLINE, Google Scholar) with search terms targeting specific coating technologies (phosphorylcholine, PMEA, hydrophilic polymer coating, fibrin-heparin) and device names (Pipeline Shield, FRED-X, p48/p64-HPC, DERIVO 2heal). We included studies that evaluated coating mechanisms, preclinical results, and clinical outcomes in retrospective, prospective, or randomized settings. Key Content and Findings: This review covers four main coated FDs: Pipeline Shield, FRED-X, p48/p64-HPC, and DERIVO 2heal. Phosphorylcholine-coated Pipeline devices have demonstrated good in vitro hemocompatibility and animal-model endothelialization, though clinical outcomes under SAPT remain mixed. PMEA-coated FRED-X shows promising safety and occlusion rates under DAPT cover with lower thromboembolic complications than uncoated FRED. HPC-coated p48/p64 effectively reduces thrombus formation in vitro. Observational studies have reported favorable outcomes with this device when used with P2Y12 inhibitors, as SAPT. The fibrin-heparin-coated DERIVO 2heal has shown encouraging early safety data, though current evidence is limited to a few retrospective studies. Across devices, long-term healing data and prospective randomized SAPT trials are still emerging. Conclusions: Surface-modified FDs offer promising safety profiles and hold potential for expanding the indications of flow diversion, especially by enabling treatment under SAPT in patients who are poor candidates for DAPT. However, when used under standard DAPT, the reduction in thromboembolic complications compared to uncoated FDs appears modest. The primary advantage of these technologies may therefore lie in facilitating safer treatment in high-risk clinical contexts. Further prospective trials are needed to validate their impact on endothelialization and long-term outcomes.