APHP, Department of Neurology and Stroke center, Bichat Hospital, INSERM LVTS-U1148, DHU FIRE, University of Paris, France (P.A., H.C., P.C.L., E.M.).
Asan Medical Center, Seoul, South Korea (J.S.K.).
Stroke. 2022 Feb;53(2):457-462. doi: 10.1161/STROKEAHA.121.035846. Epub 2021 Dec 29.
Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH.
Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of <70 mg/dL or 100±10 mg/dL, using statin or ezetimibe.
Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38-4.04] and 2.32/1000 patient-years [95% CI, 1.61-3.03], respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01-6.31], =0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00-5.62], =0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH.
Targeting an LDL cholesterol of <70 mg/dL compared with 100±10 mg/dL in patients with atherosclerotic ischemic stroke nonsignificantly increased the risk of ICH. Incident ICHs were not associated with low LDL cholesterol. Uncontrolled hypertension and anticoagulant therapy were associated with ICH which has important clinical implications. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.
尽管他汀类药物在缺血性脑卒中的二级预防中有效，但在某些情况下，它们也会增加颅内出血（ICH）的风险。在 TST 试验（靶向治疗脑卒中）中，我们预先设定了对ICH 事件预测因素的探索。
在过去 3 个月内发生缺血性脑卒中或过去 15 天内发生短暂性脑缺血发作，且有脑血管或冠状动脉粥样硬化证据的患者，按照 1:1 的比例随机分配，接受他汀类药物或依折麦布治疗，目标 LDL（低密度脂蛋白）胆固醇分别为<70mg/dL 或 100±10mg/dL。
在纳入的 2860 例患者中，中位随访 3 年后发生 31 例 ICH（较低和较高目标组分别为 13 和 18 例，每 1000 例患者年发生率分别为 3.21[95%CI：2.38-4.04]和 2.32[95%CI：1.61-3.03]）。尽管 ICH 无基线预测因素，但未控制的高血压（HR：2.51[95%CI：1.01-6.31]，=0.041）和试验期间使用抗凝剂（HR：2.36[95%CI：1.00-5.62]，=0.047）是显著的预测因素。治疗期间 LDL 胆固醇低并不是 ICH 的预测因素。
与目标 LDL 胆固醇 100±10mg/dL 相比，将动脉粥样硬化性缺血性脑卒中患者的 LDL 胆固醇目标值降至<70mg/dL，ICH 的风险增加无统计学意义。ICH 事件与 LDL 胆固醇无关。未控制的高血压和抗凝治疗与 ICH 相关，这具有重要的临床意义。
网址：https://www.clinicaltrials.gov；唯一标识符：NCT01252875；EUDRACT 标识符：2009-A01280-57。
