The Source for Neurovascular News and Education

August 15, 2020


Statins may be protective against rupture, researchers say, calling for an RCT to test this possibility.


Both HDL cholesterol level and use of lipid-lowering agents are inversely correlated with rupture among patients with intracranial aneurysms, according to an analysis published online April 5, 2018, ahead of print in Stroke. The authors hope the study will act as a springboard for a randomized trial evaluating the role of statin therapy in the prevention of aneurysm rupture.


Lead author Rose Du, MD, PhD (Brigham and Women’s Hospital, Boston, MA), pointed out to Neurovascular Exchange that there are currently no medical treatments that prevent the formation or progression of aneurysms.


“A medication that decreases the risk of rupture would increase the safety of aneurysms that are followed and decrease the number of patients that require invasive treatment,” she noted. Previous studies exploring the role of statins for this indication have yielded conflicting results.


The investigators evaluated the medical records of 4,701 patients with 6,411 intracranial aneurysms that were diagnosed at Massachusetts General Hospital and Brigham and Women’s Hospital between 1990 and 2016.


Propensity score-weighted multivariate analysis revealed an inverse relationship between the use of lipid lowering agents and rupture of aneurysms (OR 0.58; 95% CI 0.47-0.71).


In a subgroup propensity score-weighted multivariate analysis of 550 patients for whom complete information was available, both higher levels of HDL cholesterol and use of lipid lowering agents were significantly inversely associated with rupture. Lipid-lowering agents were defined as statins, vitamin B3 (niacin, nicotinic acid), fibrates, 2-azetidinones, bile acid sequestrants, and omega-3 acids. No significant association was found between rupture status and either LDL cholesterol or total cholesterol.


Predictors of Aneurysm Rupture on Weighted Multivariate Analysis


OR (95% CI)

P Value

HDL Cholesterol

0.95 (0.93-0.98)


LDL Cholesterol

1.00 (0.97-1.02)


Total Cholesterol

1.00 (0.97-1.02)


Use of Lipid Lowering Agent

0.41 (0.23-0.73)

< 0.01


“Our findings indicate that statins may be a potential medical option for decreasing the risk of rupture in brain aneurysms,” Du concluded. “While our study shows that statins may be promising, a randomized controlled trial will be necessary before a standard recommendation can be made. We hope that our results will pave the way towards such a trial.”


The current analysis represents the largest case-control study yet on the effect of lipid-lowering agents on aneurysmal subarachnoid hemorrhage, the researchers report, noting that its results are consistent with those of various experimental animal models demonstrating that statin use in rodents with intracranial aneurysms was associated with a decreased risk of aneurysm formation, growth, and rupture.”


In terms of mechanism, they suggest “statins may enhance endothelial function and attenuate oxidative stress and inflammation in the vascular wall.”




Can A, Castro VM, Dligach D, et al. Lipid-lowering agents and high HDL (high-density lipoprotein) are inversely associated with intracranial aneurysm rupture. Stroke. 2018;Epub ahead of print.



  • This study was supported by Partners Personalized Medicine.
  • Du reports no relevant conflicts of interest.