Aspirin Effect on Aneurysm Wall Enhancement: Clinical Study and Animal-model Validation Study
Elena Sagues Sese1, Diego Ojeda1, Sebastian Sanchez Herrera2, Arshaq Saleem3, Ariel Vargas1, Carlos Dier1, Samantha Saenz1, Ramanthan Kadiervel4, David Hasan5, Edgar Samaniego6
1Neurology, University of Iowa Hospitals and Clinics, 2Yale University, 3University of Iowa Carver College of Medicine, 4Neurosurgery, Mayo Clinic, 5Neurosurgery, Duke University, 6University of Iowa Hospital and Clinics
Objective:

To assess the effect of aspirin on aneurysm wall enhancement (AWE) in humans and an animal model.

Background:

Unruptured intracranial aneurysm (UIAs) affect approximately 3-5% of the global population. AWE is a potential biomarker that is associated with aneurysm instability and higher risk of rupture. AWE is increased in regions of the aneurysm wall where inflammatory cells are more prevalent. Aspirin may decrease AWE due to its anti-inflammatory properties.

Design/Methods:

Patients with IAs were analyzed for the use of aspirin, which was defined as a daily intake for at least 5 months. AWE was quantified objectively using metrics that characterize the distribution of signal intensity: 3D-AWE, focal AWE (FAWE) and specific (SAWE). These metrics, along with morphological aneurysm measurements, were analyzed for their association with aspirin consumption. A rabbit-based animal model was used to study the effects of aspirin. Aneurysms were induced with elastase as has been previously described. Four animals received aspirin for 8 weeks and were compared with 4 sham animals. Each rabbit underwent histological and high-resolution imaging to determine the presence of enhancement and inflammatory cells.

Results:

UIAs of patients who were exposed to aspirin had lower AWE= 3D-AWE (median=0.55, IQR=0.27) and FAWE (median=1.02, IQR=0.66) compared to non-exposed patients (median=0.72, IQR=0.28, p=0.027; and median=1.30, IQR=0.47, p=0.030, respectively). Among rabbits exposed to aspirin, the mean AWE was lower at 8 weeks compared to the controls (2.11 ± 0.15 vs 2.15 ± 0.37). Immunostaining of the aneurysm wall in rabbits that received aspirin revealed an absence of CD68+ or COX-2+ cells.

Conclusions:

Aspirin therapy is associated with an objective reduction in AWE, suggesting a potential role in lowering the risk of aneurysm rupture.   

10.1212/WNL.0000000000206305