Lipophilic Statins and the Risk of Intracranial Hemorrhage Following Ischemic Stroke: A Population-Based Study

Background Statins are commonly prescribed for the secondary prevention of ischemic stroke, but there is conflicting evidence as to whether they increase the risk of intracranial hemorrhage. Lipophilic statins cross the blood–brain barrier more freely than hydrophilic statins and may therefore increase the risk of intracranial hemorrhage. Objective To determine whether, in older patients following ischemic stroke, receipt of lipophilic statins was associated with differences in the risk of intracranial hemorrhage. Methods We conducted a population-based nested case-control study linking multiple healthcare databases between 1 April, 2001 and 31 March, 2015 in Ontario, Canada. Cases were Ontarians aged 66 years or older receiving a statin within 100 days preceding the development of intracranial hemorrhage within 1 year following ischemic stroke. Each case was matched with up to four controls who experienced ischemic stroke not complicated by intracranial hemorrhage but who also received a statin. We classified statins as lipophilic (atorvastatin, simvastatin, lovastatin, fluvastatin, and cerivastatin) or hydrophilic (pravastatin and rosuvastatin) based on their octanol/water partition coefficients. We calculated the odds ratio for the association between intracranial hemorrhage and receipt of lipophilic statins, with hydrophilic statins as the reference group. Results We identified 2766 individuals who experienced intracranial hemorrhage during statin therapy after ischemic stroke and 11,060 matched controls. Relative to hydrophilic statins, lipophilic statins were not associated with an increased risk of intracranial hemorrhage (adjusted odds ratio 1.07; 95% confidence interval 0.97–1.19). Conclusion Among patients treated with a statin following ischemic stroke, the risk of intracranial hemorrhage is not influenced by statin lipophilicity.