From the Research Unit for Neurology (N.J.B., S.M.H., M.M.J., S.F., A.S., D.G.), Departments of Radiology (J.A.B., M.T.E., F.S.G.H., O.G.) and Clinical Research (S.M.), and the Open Patient Data Explorative Network (OPEN) (A.C., S.M.), Odense University Hospital, University of Southern Denmark; Department of Clinical Pharmacology (D.M.), Pharmacy and Environmental Medicine, University of Southern Denmark; Centro Espanõl Investigación Farmacoepidemiológica (L.A.G.R.), Madrid, Spain; Centre for Clinical Brain Sciences (R.A.-S.S.), University of Edinburgh, United Kingdom; and Department of Neurology and Kentucky Neuroscience Institute (L.B.G.), University of Kentucky, Lexington.
Neurology. 2023 Mar 7;100(10):e1048-e1061. doi: 10.1212/WNL.0000000000201664. Epub 2022 Dec 7.
A 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.
We 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.
We 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; 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; 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.
We 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.
他汀类药物的使用与脑出血（ICH）之间的因果关系尚不确定。我们假设，长期他汀类药物暴露与 ICH 风险之间的关联可能因不同的 ICH 部位而有所不同。
我们使用丹麦全国性的登记处进行了这项分析。在南丹麦地区（人口 120 万），我们确定了 2009 年至 2018 年期间年龄在 55 岁以上的所有首次 ICH 患者。有医疗记录证实的诊断的患者被分类为出现皮质下或非皮质下 ICH，并按年龄、性别和日历年份与普通人群对照进行匹配。我们使用全国性处方登记处确定了之前的他汀类药物和其他药物的使用情况，并按近期、持续时间和强度进行了分类。使用调整了潜在混杂因素的条件逻辑回归，我们计算了皮质下和非皮质下 ICH 风险的调整比值比（aOR）和相应的 95%置信区间。
我们确定了 989 例皮质下 ICH（52.2%为女性，平均年龄为 76.3 岁）患者，与 39500 例对照和 1175 例非皮质下 ICH（46.5%为女性，平均年龄为 75.1 岁）患者相匹配，与 46755 例对照相匹配。当前使用他汀类药物与皮质下（aOR 0.83；95%CI，0.70-0.98）和非皮质下 ICH（aOR 0.84；95%CI，0.72-0.98）的风险降低相关。他汀类药物使用时间较长也与皮质下（<1 年：aOR 0.89；95%CI，0.69-1.14；≥1 年至<5 年：aOR 0.89；95%CI，0.73-0.99；≥5 年：aOR 0.67；95%CI，0.51-0.87；趋势 P=0.040）和非皮质下 ICH（<1 年：aOR 1.00；95%CI，0.80-1.25；≥1 年至<5 年：aOR 0.88；95%CI，0.73-1.06；≥5 年：aOR 0.62；95%CI，0.48-0.80；趋势 P<0.001）的风险降低相关。按他汀类药物强度分层的估计值与低-中强度治疗的主要估计值相似（皮质下 aOR 0.82；非皮质下 aOR 0.84）；高强度治疗的相关性为中性。
我们发现他汀类药物的使用与 ICH 风险降低相关，尤其是与较长的治疗时间相关。这种关联与血肿部位无关。
