APHP, Department of Neurology and Stroke Center, Bichat Hospital, INSERM LVTS-U1148, DHU FIRE, University of Paris, France (P.A., P.C.L., H.C., E.M.).
Population Health Research Institute, MacMaster University, Hamilton, Ontario, Canada (P.A.).
Stroke. 2023 Aug;54(8):1993-2001. doi: 10.1161/STROKEAHA.123.042621. Epub 2023 Jun 28.
Whether a strategy to target an LDL (low-density lipoprotein) cholesterol <70 mg/dL is more effective when LDL is reduced >50% from baseline rather than <50% from baseline has not been investigated.
The Treat Stroke to Target trial was conducted in France and South Korea in 61 sites between March 2010 and December 2018. 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 to a target LDL cholesterol of <70 mg/dL or 100±10 mg/dL, using statin and/or ezetimibe as needed. We used the results of repeated LDL measurements (median, 5 [2-6] per patient) during 3.9 years (interquartile range, 2.1-6.8) of follow-up. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time-varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event.
Among 2860 patients enrolled, patients in the lower target group who had >50% LDL cholesterol reduction from baseline during the trial had a higher baseline LDL cholesterol and a lower LDL cholesterol achieved as compared to patients who had <50% LDL cholesterol reduction (155±32 and 62 mg/dL versus 121±34 and 74 mg/dL, respectively, <0.001 for both). In the <70 mg/dL target group, patients with >50% LDL reduction had a significant reduction in the primary outcome as compared to the higher target group (hazard ratio, 0.61 [95% CI, 0.43-0.88]; =0.007) and patients with <50% LDL reduction from baseline had little reduction (hazard ratio, 0.96 [95% CI, 0.73-1.26]; =0.75).
In this post hoc analysis of the TST trial, targeting an LDL cholesterol of <70 mg/dL reduced the risk of primary outcome compared with 100±10 mg/dL provided LDL cholesterol reduction from baseline was superior to 50%, thereby suggesting that the magnitude of LDL cholesterol reduction was as important to consider as the target level to achieve.
URL: https://www.
gov; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu; Unique identifier: EUDRACT2009-A01280-57.
从基线降低 LDL(低密度脂蛋白)胆固醇>50%而非<50%时,将 LDL 靶向<70mg/dL 的策略是否更有效,尚未进行研究。
Treat Stroke to Target 试验于 2010 年 3 月至 2018 年 12 月在法国和韩国的 61 个地点进行。在过去 3 个月内发生缺血性卒中或在过去 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,随机分配至 LDL 胆固醇目标值<70mg/dL 或 100±10mg/dL 组,使用他汀类药物和/或依折麦布降脂治疗。我们使用了在 3.9 年(中位数 5[2-6]次/患者)随访期间重复 LDL 测量(中位数 5[2-6]次/患者)的结果。主要结局为缺血性卒中、心肌梗死、新出现需要紧急冠状动脉或颈动脉血运重建的症状和血管性死亡的复合结局。Cox 回归模型包括降脂治疗作为随时间变化的变量,经过随机分组策略、年龄、性别、起始事件(卒中和短暂性脑缺血发作)和起始事件后时间的调整。
在 2860 名入组患者中,与 LDL 胆固醇从基线降低<50%的患者相比,在试验期间 LDL 胆固醇从基线降低>50%的低目标组患者的基线 LDL 胆固醇更高,且达到的 LDL 胆固醇更低(分别为 155±32 和 62mg/dL 与 121±34 和 74mg/dL,均<0.001)。在 LDL 胆固醇<70mg/dL 的目标组中,与较高的目标组相比,LDL 胆固醇降低>50%的患者主要结局显著降低(风险比 0.61[95%CI,0.43-0.88];=0.007),而 LDL 胆固醇从基线降低<50%的患者的降低幅度较小(风险比 0.96[95%CI,0.73-1.26];=0.75)。
在 TST 试验的事后分析中,与 100±10mg/dL 相比,将 LDL 胆固醇靶向<70mg/dL 可降低主要结局的风险,前提是 LDL 胆固醇从基线的降低优于 50%,因此提示 LDL 胆固醇降低的幅度与目标水平同样重要。
NCT01252875。网址:https://clinicaltrialsregister.eu;唯一标识符:EUDRACT2009-A01280-57。