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August 16, 2022; 99 (7) Research Articles

Association of Long-term Statin Use With the Risk of Intracerebral Hemorrhage

A Danish Nationwide Case-Control Study

View ORCID ProfileDaniel Albjerg Rudolph, View ORCID ProfileStine Munk Hald, View ORCID ProfileLuis Alberto García Rodríguez, Sören Möller, Jesper Hallas, View ORCID ProfileLarry B. Goldstein, View ORCID ProfileDavid Gaist
First published May 16, 2022, DOI: https://doi.org/10.1212/WNL.0000000000200713
Daniel Albjerg Rudolph
From the Research Unit for Neurology (D.A.R., S.M.H., D.G.), Odense University Hospital; University of Southern Denmark (D.A.R., S.M.H., S.M.H.), Denmark; Centro Espanõl Investigación Farmacoepidemiológica (L.A.G.R.), Madrid, Spain; Open Patient Data Explorative Network (OPEN) (S.M.), Odense University Hospital; Department of Clinical Research (S.M.), University of Southern Denmark, Odense; Department of Clinical Pharmacology, Pharmacy and Environmental Medicine (J.H.), University of Southern Denmark; and Department of Neurology and Kentucky Neuroscience Institute (L.B.G.), University of Kentucky, Lexington.
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Stine Munk Hald
From the Research Unit for Neurology (D.A.R., S.M.H., D.G.), Odense University Hospital; University of Southern Denmark (D.A.R., S.M.H., S.M.H.), Denmark; Centro Espanõl Investigación Farmacoepidemiológica (L.A.G.R.), Madrid, Spain; Open Patient Data Explorative Network (OPEN) (S.M.), Odense University Hospital; Department of Clinical Research (S.M.), University of Southern Denmark, Odense; Department of Clinical Pharmacology, Pharmacy and Environmental Medicine (J.H.), University of Southern Denmark; and Department of Neurology and Kentucky Neuroscience Institute (L.B.G.), University of Kentucky, Lexington.
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Luis Alberto García Rodríguez
From the Research Unit for Neurology (D.A.R., S.M.H., D.G.), Odense University Hospital; University of Southern Denmark (D.A.R., S.M.H., S.M.H.), Denmark; Centro Espanõl Investigación Farmacoepidemiológica (L.A.G.R.), Madrid, Spain; Open Patient Data Explorative Network (OPEN) (S.M.), Odense University Hospital; Department of Clinical Research (S.M.), University of Southern Denmark, Odense; Department of Clinical Pharmacology, Pharmacy and Environmental Medicine (J.H.), University of Southern Denmark; and Department of Neurology and Kentucky Neuroscience Institute (L.B.G.), University of Kentucky, Lexington.
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Sören Möller
From the Research Unit for Neurology (D.A.R., S.M.H., D.G.), Odense University Hospital; University of Southern Denmark (D.A.R., S.M.H., S.M.H.), Denmark; Centro Espanõl Investigación Farmacoepidemiológica (L.A.G.R.), Madrid, Spain; Open Patient Data Explorative Network (OPEN) (S.M.), Odense University Hospital; Department of Clinical Research (S.M.), University of Southern Denmark, Odense; Department of Clinical Pharmacology, Pharmacy and Environmental Medicine (J.H.), University of Southern Denmark; and Department of Neurology and Kentucky Neuroscience Institute (L.B.G.), University of Kentucky, Lexington.
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Jesper Hallas
From the Research Unit for Neurology (D.A.R., S.M.H., D.G.), Odense University Hospital; University of Southern Denmark (D.A.R., S.M.H., S.M.H.), Denmark; Centro Espanõl Investigación Farmacoepidemiológica (L.A.G.R.), Madrid, Spain; Open Patient Data Explorative Network (OPEN) (S.M.), Odense University Hospital; Department of Clinical Research (S.M.), University of Southern Denmark, Odense; Department of Clinical Pharmacology, Pharmacy and Environmental Medicine (J.H.), University of Southern Denmark; and Department of Neurology and Kentucky Neuroscience Institute (L.B.G.), University of Kentucky, Lexington.
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Larry B. Goldstein
From the Research Unit for Neurology (D.A.R., S.M.H., D.G.), Odense University Hospital; University of Southern Denmark (D.A.R., S.M.H., S.M.H.), Denmark; Centro Espanõl Investigación Farmacoepidemiológica (L.A.G.R.), Madrid, Spain; Open Patient Data Explorative Network (OPEN) (S.M.), Odense University Hospital; Department of Clinical Research (S.M.), University of Southern Denmark, Odense; Department of Clinical Pharmacology, Pharmacy and Environmental Medicine (J.H.), University of Southern Denmark; and Department of Neurology and Kentucky Neuroscience Institute (L.B.G.), University of Kentucky, Lexington.
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David Gaist
From the Research Unit for Neurology (D.A.R., S.M.H., D.G.), Odense University Hospital; University of Southern Denmark (D.A.R., S.M.H., S.M.H.), Denmark; Centro Espanõl Investigación Farmacoepidemiológica (L.A.G.R.), Madrid, Spain; Open Patient Data Explorative Network (OPEN) (S.M.), Odense University Hospital; Department of Clinical Research (S.M.), University of Southern Denmark, Odense; Department of Clinical Pharmacology, Pharmacy and Environmental Medicine (J.H.), University of Southern Denmark; and Department of Neurology and Kentucky Neuroscience Institute (L.B.G.), University of Kentucky, Lexington.
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Association of Long-term Statin Use With the Risk of Intracerebral Hemorrhage
A Danish Nationwide Case-Control Study
Daniel Albjerg Rudolph, Stine Munk Hald, Luis Alberto García Rodríguez, Sören Möller, Jesper Hallas, Larry B. Goldstein, David Gaist
Neurology Aug 2022, 99 (7) e711-e719; DOI: 10.1212/WNL.0000000000200713

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Abstract

Background and Objectives A causal relationship between long-term statin use and the risk of intracerebral hemorrhage (ICH) remains uncertain. We investigated the association with statin use before hospital admission for ICH in a Danish population–based, nationwide case-control study.

Methods We used the Danish Stroke Registry to identify all patients aged 45 years or older with a first-ever ICH between 2005 and 2018. Patients with ICH were matched for age, sex, and calendar year to controls selected from the general population. A medication registry with information on all dispensed prescriptions at community pharmacies in Denmark since 1995 was used to ascertain previous statin exposure that was classified for recency, duration, and intensity. Using conditional regression and adjusting for potential confounders, we calculated adjusted odds ratios (aORs) and corresponding 95% CIs for the risk of ICH.

Results The study population consisted of 16,235 patients with ICH and 640,943 controls. Current statin use (cases 25.9% vs controls 24.5%; aOR 0.74, 95% CI, 0.71–0.78) and a longer duration of current statin use (<1 year: aOR 0.86; 95% CI, 0.81–0.92; ≥1 to <5 years: aOR 0.72; 95% CI, 0.68–0.76; ≥5 to <10 years: aOR 0.65; 95% CI, 0.60–0.71; ≥10 years of use, 0.53; 95% CI 0.45–0.62; p for trend <0.001) were associated with a lower risk of ICH. Similar treatment duration relationships were found in analyses stratified by statin use intensity (high-intensity therapy: <1 year of use: aOR 0.78; 95% CI, 0.66–0.93; ≥10 years of use: aOR 0.46; 95% CI 0.33–0.65; p for trend 0.001).

Discussion We found that a longer duration of statin use was associated with a lower risk of ICH.

Classification of Evidence This study provides Class II evidence that current statin use and a longer duration of statin use are each associated with a lower risk of ICH.

Glossary

aOR=
adjusted odds ratio;
DSR=
Danish Stroke Registry;
HPS=
Heart Protection Study;
ICH=
intracerebral hemorrhage;
IS=
ischemic stroke;
PCSK9I=
proprotein convertase subtilisin kexin 9 inhibitor;
SES=
socioeconomic status;
SPARCL=
Stroke Prevention with Aggressive Reduction in Cholesterol Level;
TIA=
transient ischemic attack

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was José Merino, MD, MPhil.

  • Class of Evidence NPub.org/coe

  • CME Course NPub.org/cmelist

  • Received November 17, 2021.
  • Accepted in final form March 24, 2022.
  • © 2022 American Academy of Neurology
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