Aspirin as a Promising Agent for Decreasing Incidence of Cerebral Aneurysm Rupture

Abstract

Background and Purpose Chronic inflammation is postulated as an important phenomenon in intracranial aneurysm (IA) wall pathophysiology. This study was conducted to determine if aspirin use impacts the occurrence of IA rupture. Methods Subjects enrolled in the International Study of Unruptured Intracranial Aneurysms (ISUIA) were selected from the prospective untreated cohort (n=1691) in a nested case-control study. Cases were subjects who subsequently suffered a proven aneurysmal SAH during a 5-year follow-up period. Four controls were matched to each case by site and size of aneurysm (58 cases, 213 controls). Frequency of aspirin use was determined at baseline interview. Aspirin frequency groups were analyzed for risk of aneurysmal hemorrhage. Bivariable and multivariable analyses were performed using conditional logistic regression. Results A trend of a protective effect for risk of UIA rupture was observed. Patients who used aspirin 3x weekly - daily had an odds ratio (OR) for hemorrhage of 0.40 [95% CI=0.18-0.87, reference group = no use of aspirin], patients in the “< once a month” group had an OR of 0.80 (95% CI=0.31-2.05) and patients in the “> once a month – 2x/week” group had an OR of 0.87 (95% CI=0.27-2.81) (p= 0.025). In multivariable risk factor analyses, patients who used aspirin three times weekly to daily had a significantly lower odds of hemorrhage (Adjusted OR=0.27, 95% CI 0.11-0.67, p=0.03) compared to those who never take aspirin. Conclusions Frequent aspirin use may confer a protective effect for risk of IA rupture. Future investigation in animal models and clinical studies is needed.

Angiotensin-(1-7) Protects against the Development of Aneurysmal Subarachnoid Hemorrhage in Mice

“…Excessive inflammation has been suggested as a key mechanism for the development of aneurysmal rupture in previous studies. 2,23,24 Although we confirmed the requirement of AT2R in the protective effect of Ang-(1-7) using AT2R knockout mice, the requirement of Mas receptor in this context remains to be further elucidated. Although our pharmacological study using standard and high doses of the Mas receptor antagonist strongly suggested that the activation of Mas receptor is not a prerequisite for the protective role of Ang-(1-7), we did not confirm this finding using Mas receptor knockout mice.…”

“…1 Inflammation is emerging as a key player in the processes that lead to aneurysmal rupture. [2][3][4] Therefore, the pharmacological prevention of aneurysmal rupture that targets inflammation may be an attractive approach for patients with inoperable unruptured aneurysms.…”

Inflammation in human cerebral aneurysms: pathogenesis, diagnostic imaging, genetics, and therapeutics

“…Hasan et al [57] investigated the anti-inflammatory effect of acetylsalicylic acid (aspirin) on the progression of aneurysm to rupture. A secondary analysis of the ISUIA study revealed that the aspirin decreased patients' risk of aneurysm rupture by 60%.…”

“…Taken together, these findings suggest that low doses of aspirin (81 mg daily for 3 months) may effectively attenuate inflammation in IA, preventing acute SAH. [57] Angiotensin 1-7 has also been explored as a potential therapeutic option as Ang 1-7 is an antagonist to Ang 2. Ang 2 has been shown to increase the expression of various pro-inflammatory cytokines as well as promote blood vessel extracellular matrix remodeling.…”

Unruptured Intracranial Aneurysms: Some Questions Answered, Many Questions Remain

“…Despite the data nicely summarized by Dr. Pelz, numerous important questions remain regarding the management of UIAs: 1) do we have valid and reliable aneurysm-location and sizespecific natural history data for the spectrum of UIAs so commonly seen in clinical practice, 2) do we have contemporary data regarding the objective outcomes-included death and major functional and cognitive morbidities-for surgical and endovascular management of UIAs, 3) if we manage conservatively, what is the risk of UIA growth (which should likely mandate surgical or endovascular intervention), 4) are there aneurysm characteristics, beyond those published in the available observation studies and in the realm of morphological characteristics and computational fluid dynamics, which might assist us in defining the long term rupture risks at the time of UIA detection, 5) in the absence of a clinical trial, can we directly compare the available natural history and interventional data via some other analytic approach, such as a propensity analysis, 6) are there genotypic predictors of aneurysm occurrence, rupture, growth and morphology change, or biomarkers and genotypic predictors of outcome of aneurysm management, 7) is there clinical equipoise in the management of some subgroup of patients with UIAs such that a randomized clinical trial should be performed and what would be the best design of such a trial, 8) given that cigarette smoking and hypertension are risk factors for subarachnoid hemorrhage in general and for UIA formation, would aggressive treatment of these risk factors lower the likelihood of rupture, and 9) are there medical treatments such as aspirin 25 that could conceivably lower the risk of aneurysm rupture?…”