Rosuvastatin for intracranial aneurysms treated with flow diverters: preclinical study in rabbits

Flow diverters (FDs) revolutionized cerebral aneurysm treatment by promoting aneurysm sac sealing but have limitations, including thromboembolic complications and incomplete occlusion. Rosuvastatin enhances endothelialization via endothelial progenitor cell mobilization and nitric oxide bioavailability, potentially improving FD healing. This study assessed the effect of rosuvastatin on FD endothelialization in a rabbit aneurysm model.

Twenty-two rabbits with elastase-induced aneurysms underwent FD implantation in the right subclavian artery. In the same animals, FDs were placed in the descending aorta to assess side branch patency. Thirteen rabbits received rosuvastatin plus aspirin (Rosu+ASA; 10 mg/kg/day each) and nine received aspirin alone (ASA; 10 mg/kg/day). Two weeks post-implantation, aneurysm occlusion (O'Kelly-Marotta scale), side branch patency (high frequency optical coherence tomography), and histological/MPM strut coverage were evaluated. Rosuvastatin serum concentration was correlated with endothelial cell coverage.

Complete aneurysm occlusion (OKM D) occurred in 11/13 (84.6%) of Rosu+ASA vs 6/9 (66.6%) of ASA animals. Patency of branches ≥1 mm was higher with Rosu+ASA (17/18 (94.4%) vs 9/13 (46.1%), PP=0.007), as was patency of branches <1 mm (21/22 (95.4%) vs 11/15 (73.4%), P=0.036). The composite outcome (complete occlusion+patent branches) favored Rosu+ASA (10/13 (76.9%) vs 2/9 (22.2%), P=0.011). Histology showed a trend toward greater strut coverage and neointimal thickness in Rosu+ASA (P=0.1). Rosuvastatin serum concentration strongly correlated with endothelial cell coverage (r=0.92, P=0.02).

In rabbit FD models, rosuvastatin therapy seems to improve aneurysm occlusion, preserving side branch patency. We also found an association between drug levels and endothelial cells covering the FD. These findings support further investigations.