Candidate Compounds for Drug-Device Hybrid Therapies in the Management of Abdominal Aortic Aneurysm (AAA) Disease

Objective: AAA is a common and potentially lethal condition. Endovascular aneurysm repair (EVAR) reduces morbidity but is less durable than open repair secondary to continued remodeling of the diseased aorta. Local delivery of compounds inhibiting degeneration of the neck and promoting sac regression may stabilize endografts and improve durability. Our objective was to determine if HMG-CoA reductase inhibitors (statins) and angiotensin receptor blockers (ARBs) are appropriate candidates for drug-device hybrid therapies based on their efficacy in experimental AAA attenuation. Methods: Apo E−/− male mice were infused with angiotensin (Ang) II (1.0 mg/kg/min) via minipumps. Statin (n = 6; 40 mg/kg/d), ARB1 (n = 6; 50 mg/kg/d), and ARB2 (n = 6; 10 mg/kg/d) were administered via drinking water (statin) or chow (ARBs) and compared with control mice treated with Ang II alone (n = 6). Aortic diameter was serially determined with ultrasonography. Mice were sacrificed 28 days after pump implantation. Immunohistochemistry was performed to evaluate aortic elastin preservation, medial SMC maintenance, and mural inflammation and neovascularization. Patterns of gene expression were determined via qPCR. Serum drug concentrations were quantified on the day of sacrifice. Results: Multiple dissections (n = 4) and ruptures (n = 3) occurred in control animals. None were observed in statin- or ARB-treated mice. Statin (1.30 ± 0.19 mm), ARB1 (1.17 ± 0.12 mm), and ARB2 (1.13 ± 0.05 mm) treatment significantly attenuated aortic dilatation compared with control (1.69 ± 0.46 mm; P < .05; Fig). Histologic, biomarker, and serologic analyses were not complete at the time of submission. Conclusions: Statins and ARBs inhibit experimental AAA progression. Further histologic and biomarker analysis is forthcoming and will aid in the determination of mechanisms of statin and ARB aneurysm inhibition. Local delivery of these compounds may limit endograft failure via inhibition of aortic remodeling after AAA exclusion.