Small Unruptured Aneurysm Verification-prevention Effect against Growth of Cerebral Aneurysm Study Using Statin

Abstract

Several basic experimental studies have demonstrated that statins have beneficial effects for intracranial aneurysm (IA). Clinical studies on unruptured IAs, however, remain limited to four retrospective studies that have reached different conclusions. This study was the first open-label, multicenter, randomized controlled trial to assess the preventive effects of atorvastatin. Patients with unruptured small saccular IAs were randomly assigned to statin and control groups. The primary endpoint was a composite of aneurysm growth of ≥0.5 mm, new bleb formation confirmed from magnetic resonance (MR) angiography, and rupture. Enrollment was prematurely terminated due to unexpectedly slow enrollment. Of 231 patients (275 target IAs), 110 patients (128 IAs) were randomly assigned to the statin group and 121 patients (147 IAs) to the control group. After excluding 22 dropout patients, 107 IAs in the 93 statin group patients and 140 IAs in the 116 control group patients were finally analyzed. No significant differences of basic characteristics were evident between groups, except for significantly higher systolic pressure in the statin group (P = 0.03). The primary endpoint occurred in 28 IAs (20.0%) in the control group and in 17 IAs (15.9%) in the statin group. No aneurysm rupture was confirmed in either group. Significant beneficial effects of statin for IAs were not demonstrated for the primary endpoint (log-rank P = 0.359). This randomized trial did not establish any preventive effects of atorvastatin for unruptured small IAs. Further studies of larger cohorts are required to clarify the efficacy of statins for patients with unruptured IAs.

European Stroke Organisation (ESO) guidelines on management of unruptured intracranial aneurysms

“…There is one completed RCT comparing treatment with a statin versus no statin on the risk of growth and rupture of an intracranial aneurysm, but this trial had no data on death or dependency as outcome measure. 65 In this open-label, multicentre, randomised controlled trial the effect of atorvastatin on the risk of aneurysm growth was studied. The primary endpoint was a composite of aneurysm growth of ⩾0.5 mm, new bleb formation confirmed from magnetic resonance (MR) angiography, and rupture.…”

Intracranial Aneurysms Induced by RUNX1 Through Regulation of NFKB1 in Patients With Hypertension-An Integrated Analysis Based on Multiple Datasets and Algorithms

“…This phenomenon further reduces the elasticity of the cerebral vascular wall, making it less able to adapt to altered hemodynamics, promotes IA progression, and increases the risk of rupture ( 59 – 61 ). NF-κB elevates the transcription of various pro-inflammatory genes such as COX-2, CCL-2, MMP , and iNOS , and the inflammatory response is involved in the progression and rupture of IA ( 62 , 63 ). Moreover, macrophage infiltration and NF-κB activation are reduced if macrophages are specifically absent or in the mutants of the NF-κB inhibitory protein.…”

Endovascular and Medical Management of Unruptured Intracranial Aneurysms

“…There was no statistically significant difference between the two treatment groups, but the study was ended prematurely due to slow enrollment. 51…”

“…There was no statistically significant difference between the two treatment groups, but the study was ended prematurely due to slow enrollment. 51 Management of hypertension is recommended for reduction of aneurysm rupture risk. While there is no prospective randomized controlled trial data yet available, one prospective study included 272 patients with unruptured intracranial aneurysms, and found that patients with uncontrolled hypertension, in comparison to nonhypertensive patients, had a high hazard ratio for aneurysm growth (6.1, 95% confidence interval [CI]: 2.4-15.4), compared with controlled hypertensive patients (1.6, 95% CI: 0.6-3.8).…”