Modernizing dual antiplatelet therapy in flow diversion: comparative outcomes after transition to universal prasugrel

BACKGROUND: Dual antiplatelet therapy (DAPT) is critical for safe flow diversion (FD), yet unlike the extensive coronary literature, FD remains less common and lacks strong evidence to guide DAPT choice. Clopidogrel's variable responsiveness has pushed clinicians towards platelet function testing and more potent agents. In 2023, our institution adopted universal prasugrel-based DAPT, and this study compares outcomes across clopidogrel, ticagrelor, and prasugrel. METHODS: We present a retrospective review of all intracranial aneurysms treated with the Pipeline Embolization Device (PED) between July 2021 and July 2024 using a prospectively maintained database. Primary outcomes were thromboembolic and hemorrhagic complications, occlusion rates, and functional outcomes (modified Rankin Scale (mRS)). Secondary analyses were conducted based on surface modification. RESULTS: A total of 243 FD procedures were performed in 229 patients (mean age 55.2 years; 84.3% women) treating 265 aneurysms. DAPT regimens included ticagrelor (38.7%), clopidogrel (31.7%), and prasugrel (29.6%). At median 12-month follow-up, 97.8% of patients achieved favorable functional outcomes (mRS ≤2), with no differences between regimens. No significant differences in aneurysm occlusion (complete/near-complete in 86.4%) were found between the DAPT regimens. Thromboembolic (4.1%) and hemorrhagic (4.9%) complications did not differ significantly; notably, all intracranial hemorrhages occurred in ticagrelor-treated patients. Retreatment rates were significantly higher in non-surface-modified versus surface-modified PEDs (8.3% vs 0.9%, P=0.01). CONCLUSIONS: Prasugrel showed comparable safety and occlusion outcomes relative to clopidogrel and ticagrelor. Our findings underscore a critical gap in the evidence base and highlight the urgent need for multicenter registries and prospective trials to establish standardized, data-driven DAPT protocols for intracranial FD.