Atorvastatin and growth, rupture of small unruptured intracranial aneurysm: results of a prospective cohort study

Background and aims: The role of statins in unruptured intracranial aneurysm (UIA) growth and rupture remains ambiguous. This study sought to determine whether atorvastatin is associated with aneurysm growth and rupture in patients harboring UIA Methods: This prospective, multicenter cohort study consecutively enrolled patients with concurrent UIA <7 mm and ischemic cerebrovascular disease from four hospitals between 2016 and 2019. Baseline and follow-up patient information was recorded. Because of the strong anti-inflammatory effect of aspirin, patients using aspirin were excluded. Patients taking atorvastatin 20 mg daily were atorvastatin users. The primary and exploratory endpoints were aneurysm rupture and growth, respectively. Results: Among the 1087 enrolled patients, 489 (45.0%) took atorvastatin, and 598 (55%) took no atorvastatin. After a mean follow-up duration of 33.0 +/- 12.5 months, six (1.2%) and five (0.8%) aneurysms ruptured in atorvastatin and non-atorvastatin groups, respectively. In the adjusted multivariate Cox analysis, UIA sized 5 to <7 mm, current smoker, and uncontrolled hypertension were associated with aneurysm rupture, whereas atorvastatin [adjusted hazard ratio (HR) 1.495, 95% confidence interval (CI) 0.417-5.356, p = 0.537] was not. Of 159 patients who had follow-up imaging, 34 (21.4%) took atorvastatin and 125 (78.6%) took no atorvastatin. Aneurysm growth occurred in five (14.7%) and 21 (16.8%) patients in atorvastatin and non-atorvastatin groups (mean follow-up: 20.2 +/- 12.9 months), respectively. In the adjusted multivariate Cox analysis, UIAs sized 5 to <7 mm and uncontrolled hypertension were associated with a high growth rate; atorvastatin (adjusted HR 0.151, 95% CI 0.031-0.729, p = 0.019) was associated with a reduced growth rate. Conclusions: We conclude atorvastatin use is associated with a reduced risk of UIA growth, whereas atorvastatin is not associated with UIA rupture. The trial registry name: The Clinic Benefit and Risk of Oral Aspirin for Unruptured Intracranial Aneurysm Combined With Cerebral Ischemia