Risk of Intracranial Hemorrhage From Statin Use | Journal Scan

Study Questions:

What is the association between statin usage and the risk of intracranial hemorrhage (ICH) in Asian subjects without a prior history of stroke?


Patients initiating statin therapy between 2005 and 2009 without a prior history of ischemic or hemorrhagic stroke were identified from Taiwan’s National Health Insurance comprehensive electronic database containing 99% of the country’s population. Participants were stratified by advanced age (≥70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH. Cox regression models were applied to estimate the hazard ratio (HR) of ICH. The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable, using the lowest quartile of cumulative dosage as a reference.


There were 1,096,547 statin initiators, with an average follow-up of 3.3 years. The adjusted HR for ICH between the highest and the lowest quartiles was nonsignificant at 1.06, with a 95% confidence interval (CI) spanning 1.00 (0.94-1.19), nor was there an increased risk with high-efficacy statins. Similar nonsignificant results were found in sensitivity analyses using different outcome definitions including risk factors for ICH and atrial fibrillation or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients in the highest cumulative statin dosage group without diagnosed hypertension (adjusted HR, 1.36; 95% CI, 1.11-1.67; p < 0.001 for interaction).


Generally, no association was observed between cumulative statin use and risk of ICH among subjects without a prior history of stroke. An increased risk was identified among the nonhypertensive cohort, but this finding should be interpreted with caution.


The findings support two recent meta-analyses that show no association between statins and an increase in ICH. Further, in this very large Asian population study, there was a dose-response relationship between cumulative dose of statin use and reduced mortality risk, as well as an inverse relationship between cumulative statin dosing and the incidence of ischemic stroke. Nonetheless, the signal of an increased risk of ICH in Asians without hypertension and at low cardiovascular risk is a concern that needs to be assessed in other populations.

Clinical Topics: Arrhythmias and Clinical EP, Dyslipidemia, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, Nonstatins, Novel Agents, Statins, Hypertension

Keywords: Atrial Fibrillation, Cardiovascular Diseases, Follow-Up Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Incidence, Intracranial Hemorrhages, National Health Programs, Primary Prevention, Risk, Risk Factors, Stroke

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