From the Research Unit for Neurology (D.G., S.M.H.), Odense University Hospital; University of Southern Denmark, Odense, Denmark; Centro Español Investigación Farmacoepidemiológica (L.A.G.R.), Madrid, Spain; Department of Clinical Pharmacology (J.H.), Pharmacy and Environmental Medicine, University of Southern Denmark; Open Patient Data Explorative Network (OPEN) (S.M.), Odense University Hospital; Odense Patient Data Explorative Network (OPEN) (B.B.H.), Odense University Hospital, Denmark; Beth Israel Deaconess Medical Center (M.S.), Harvard Medical School; and Department of Neurology and Kentucky Neuroscience Institute (L.B.G.), University of Kentucky, Lexington.
Neurology. 2023 Oct 31;101(18):e1793-e1806. doi: 10.1212/WNL.0000000000207792. Epub 2023 Aug 30.
BACKGROUND AND OBJECTIVES: Survivors of spontaneous intracerebral hemorrhage (ICH) may have indications for statin therapy. The effect of statins on the risk of subsequent hemorrhagic and ischemic stroke (IS) in this setting is uncertain. We sought to determine the risk of any stroke (ischemic stroke, IS or recurrent ICH), IS, and recurrent ICH associated with statin use among ICH survivors. METHODS: Using the Danish Stroke Registry, we identified all patients admitted to a hospital in Denmark (population 5.8 million) with a first-ever ICH between January 2003 and December 2021 who were aged 50 years or older and survived >30 days. Patients were followed up until August 2022. Within this cohort, we conducted 3 nested case-control analyses for any stroke, IS, and recurrent ICH. We matched controls for age, sex, time since first-ever ICH, and history of prior IS. The primary exposure was statin use before or on the date of subsequent stroke or the equivalent date in matched controls. Using conditional logistic regression, we calculated adjusted odds ratios (aORs) and corresponding 95% confidence intervals (CIs) for any stroke, IS, and recurrent ICH associated with statin exposure. RESULTS: We identified 1,959 patients with any stroke (women 45.3%; mean [SD] age, 72.6 [9.7] years) who were matched to 7,400 controls; 1,073 patients with IS (women 42.0%; mean [SD] age, 72.4 [10.0] years) who were matched to 4,035 controls and 984 patients with recurrent ICH (women 48.7%; mean [SD] age, 72.7 [9.2] years) who were matched to 3,755 controls. Statin exposure was associated with a lower risk of both any stroke (cases 38.6%, controls 41.1%; aOR 0.88; 95% CI 0.78-0.99) and IS (cases 39.8%, controls 41.8%, aOR 0.79; 95% CI 0.67-0.92), but was not associated with recurrent ICH risk (cases 39.1%, controls 40.8%, aOR 1.05; 95% CI 0.88-1.24). DISCUSSION: Exposure to statins was not associated with an increased risk of recurrent ICH but was associated with a lower risk of any stroke, largely due to a lower risk of IS. Confirmation of these findings in randomized trials is needed. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that statin use in patients with ICH is associated with a lower risk of any stroke and IS and not with increased risk of recurrent ICH.
背景与目的：自发性脑出血（ICH）幸存者可能有使用他汀类药物的指征。他汀类药物对这种情况下随后发生的出血性和缺血性卒中（IS）风险的影响尚不确定。我们旨在确定在 ICH 幸存者中，使用他汀类药物与任何卒中（缺血性卒中、IS 或复发性 ICH）、IS 和复发性 ICH 的风险相关。
方法：我们使用丹麦卒中登记处，确定了 2003 年 1 月至 2021 年 12 月期间在丹麦一家医院（580 万人口）首次发生 ICH 的年龄在 50 岁或以上且存活时间超过 30 天的所有患者。患者随访至 2022 年 8 月。在此队列中，我们进行了 3 项嵌套病例对照分析，以评估任何卒中、IS 和复发性 ICH。我们为对照匹配年龄、性别、ICH 后时间和既往 IS 史。主要暴露因素是在随后的卒中或匹配对照的等效日期之前或当天使用他汀类药物。我们使用条件逻辑回归计算了与他汀类药物暴露相关的任何卒中、IS 和复发性 ICH 的调整比值比（aOR）和相应的 95%置信区间（CI）。
结果：我们确定了 1959 名患有任何卒中（女性 45.3%；平均[标准差]年龄 72.6[9.7]岁）的患者，并与 7400 名对照相匹配；1073 名患有 IS（女性 42.0%；平均[标准差]年龄 72.4[10.0]岁）的患者与 4035 名对照相匹配，984 名患有复发性 ICH（女性 48.7%；平均[标准差]年龄 72.7[9.2]岁）的患者与 3755 名对照相匹配。他汀类药物暴露与任何卒中（病例 38.6%，对照 41.1%；aOR 0.88；95%CI 0.78-0.99）和 IS（病例 39.8%，对照 41.8%，aOR 0.79；95%CI 0.67-0.92）的风险降低相关，但与复发性 ICH 风险无关（病例 39.1%，对照 40.8%，aOR 1.05；95%CI 0.88-1.24）。
讨论：他汀类药物暴露与复发性 ICH 风险增加无关，但与任何卒中、IS 的风险降低有关，主要是因为 IS 的风险降低。需要随机试验来证实这些发现。
证据分类：本研究提供了 III 级证据，表明 ICH 患者使用他汀类药物与任何卒中、IS 的风险降低相关，与复发性 ICH 的风险增加无关。
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