Association Between Statin Use and Intracerebral Hemorrhage Location: A Nested Case-Control Registry Study

Nils Jensen Boe, Stine Munk Hald, Mie Micheelsen Jensen, Jonas Asgaard Bojsen, Mohammad Talal Elhakim, Sandra Florisson, Alisa Saleh, Anne Clausen, Sören Möller, Frederik Severin Gråe Harbo, Ole Graumann, Jesper Hallas, Luis Alberto García Rodríguez, Rustam Al-Shahi Salman, Larry B Goldstein, David Gaist

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Background and ObjectivesA causal relationship between statin use and intracerebral hemorrhage (ICH) is uncertain. We hypothesized that an association between long-term statin exposure and ICH risk might vary for different ICH locations.MethodsWe conducted this analysis using linked Danish nationwide registries. Within the Southern Denmark Region (population 1.2 million), we identified all first-ever cases of ICH between 2009 and 2018 in persons aged ≥55 years. Patients with medical record-verified diagnoses were classified as having a lobar or nonlobar ICH and matched for age, sex, and calendar year to general population controls. We used a nationwide prescription registry to ascertain prior statin and other medication use that we classified for recency, duration, and intensity. Using conditional logistic regression adjusted for potential confounders, we calculated adjusted ORs (aORs) and corresponding 95% CIs for the risk of lobar and nonlobar ICH.ResultsWe identified 989 patients with lobar ICH (52.2% women, mean age 76.3 years) who we matched to 39,500 controls and 1,175 patients with nonlobar ICH (46.5% women, mean age 75.1 years) who we matched to 46,755 controls. Current statin use was associated with a lower risk of lobar (aOR 0.83; 95% CI, 0.70-0.98) and nonlobar ICH (aOR 0.84; 95% CI, 0.72-0.98). Longer duration of statin use was also associated with a lower risk of lobar (<1 year: aOR 0.89; 95% CI, 0.69-1.14; ≥1 year to <5 years aOR 0.89; 95% CI 0.73-1.09; ≥5 years aOR 0.67; 95% CI, 0.51-0.87; p for trend 0.040) and nonlobar ICH (<1 year: aOR 1.00; 95% CI, 0.80-1.25; ≥1 year to <5 years aOR 0.88; 95% CI 0.73-1.06; ≥5 years aOR 0.62; 95% CI, 0.48-0.80; p for trend <0.001). Estimates stratified by statin intensity were similar to the main estimates for low-medium intensity therapy (lobar aOR 0.82; nonlobar aOR 0.84); the association with high-intensity therapy was neutral.DiscussionWe found that statin use was associated with a lower risk of ICH, particularly with longer treatment duration. This association did not vary by hematoma location.

Original languageEnglish
Issue number10
Pages (from-to)e1048-e1061
Publication statusPublished - 7. Mar 2023


  • Aged
  • Case-Control Studies
  • Cerebral Hemorrhage/chemically induced
  • Duration of Therapy
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects
  • Male
  • Registries


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