Association of Long-term Statin Use with the Risk of Intracerebral Hemorrhage: A Danish Nationwide Case-Control Study

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.