E-012 Coils Coated with a Statin Accelerate Intra-aneurysmal Organization

Abstract

The safety and efficacy of endovascular coil embolization of intracranial aneurysms is widely accepted. However, recurrence of aneurysms in large cases after coil embolization is a serious problem which remains to be solved. A major cause of recurrence is incomplete organization within the aneurysm. We have been developing modified coils. We read these two papers, and we found the statin reduces aneurymal size. (Am J Cardiol. 1996;97:279–280. Eur J Vasc Endovasc Surg. 2006;32:21–26.) If oral administration of a statin reduces aneurysm growth, could coils coated with a statin be more effective? This discovery was what motivated us to conduct this study. We ligated the distal External carotid artery and made an experimental aneurysm. We then inserted a coil coated with a statin to be reexamined after two and four weeks. We removed at 2 and 4 weeks after coils were implanted. In the case of implanted simvastatin coils, thick tissue had formed at the end of the coils and acted as a plug to inhibit blood flowing into the space of an aneurysm. On the other hand, in the case of the unmodified coil, blood had flowed into the space where the coil was lodged. We analyzed histochemical staining. We found endothelialization at the orifice of an experimental aneurysm, and we saw that there was proliferation of smooth muscle cells within the aneurysm. The percent of organized area of the simvastatin group was significantly higher than the unmodified coil group. We tested another 6 statins in the same way. Two weeks after coil implantation, the experimental aneurysm was cut vertically. The Aneurysmal cavity was fully filled with cellular tissue in the almost cases. In the arterial bifurcation, hemodynamic stress causes wall shear stress, endothelial dysfunction, imbalance of NO, and vascular inflammation. Vascular inflammation causes the infiltration of macrophage, increase of MMP, and destruction of ECM, Or migration of SMC. What are the effect of a statin? We suggest 4 points. First improving endothelial function, second decreasing oxidative stress, third decreasing the vascular inflammation. And fourth statin suppresses the excretion of MMP and inhibits the destruction of ECM. Coils coated with simvastatin effectively accelerated intra-aneurysmal organization and endothelialization over the coils at the orifice to ECA sacs in a rat aneurysm model. Simvastatin is widely used to lower cholesterol, so its safety is already established. We are now preparing drug-eluting coils to optimize the local concentration of simvastatin and its duration of efficacy.DisclosuresT. Kodama: None.