Statins as a Candidate of Drugs for Intracranial Aneurysm Treatment

Abstract

The treatment for intracranial aneurysm (IA) is socially important because of poor outcome posed by subarachnoid hemorrhage after rupture. Further, the incidence of IAs in general public is high and, indeed, in developed countries many IAs are incidentally found through brain check. However, to date, options for treatment of IAs to prevent rupture are quite limited only to surgical procedures such as microsurgical clipping and endovascular coiling. Taking into account unavoidable risks of complication from surgical interventions and numerous aneurysm careers without treatment, less invasive medical therapies should be established. In human IA lesions, the presence of inflammatory responses, such as expressions of pro-inflammatory mediators and infiltration of inflammatory cells, have been reported, which suggests the involvement of inflammatory responses in the pathogenesis of IA. Recent experimental studies using rodent models have revealed the crucial role of inflammatory responses mediated by NF- κ B activation in IA formation and progression and supported the notion that IA is an inflammatory disease affected intracranial arteries. To find out a candidate drug for IA treatments, the effect of several drugs with anti-inflammatory and anti-NF- κ B actions on IA progression has been examined using rodent models and revealed the excellent inhibitory effect of statins (HMG-CoA reductase inhibitors) on IA progression. Based on these findings, the case-control study was recently carried out enrolling patients with unruptured or ruptured IAs to examine the effect of statin usage on rupture. This study revealed the significant differences in the ratio of statin usage between two groups and notably the remarkable reduction of risk of rupture of pre-existing IAs under statin usage at the adjusted odds ratio of 0.30. Recent laboratory and clinical studies make considerable achievement toward the future development of drugs for IA treatment and especially suggest the potential of statins as a candidate.