Department of Neurology (A. Wang, Tian, Xie, H. Li, Jing, Lin, Yilong Wang, Zhao, Z. Li, Liu, Yongjun Wang, Meng), Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases (A. Wang, Tian, Xie, H. Li, Jing, Lin, Yilong Wang, Zhao, Z. Li, Liu, Yongjun Wang, Meng), Beijing, China; Beijing Municipal Key Laboratory of Clinical Epidemiology (A. Wang), Beijing, China; Department of Epidemiology and Health Statistics (Tian), School of Public Health, Capital Medical University, Beijing, China; Stroke Trials Unit, Mental Health and Clinical Neuroscience (Bath), University of Nottingham, Nottingham, UK; Advanced Innovation Center for Human Brain Protection (Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, Beijing, China
Department of Neurology (A. Wang, Tian, Xie, H. Li, Jing, Lin, Yilong Wang, Zhao, Z. Li, Liu, Yongjun Wang, Meng), Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases (A. Wang, Tian, Xie, H. Li, Jing, Lin, Yilong Wang, Zhao, Z. Li, Liu, Yongjun Wang, Meng), Beijing, China; Beijing Municipal Key Laboratory of Clinical Epidemiology (A. Wang), Beijing, China; Department of Epidemiology and Health Statistics (Tian), School of Public Health, Capital Medical University, Beijing, China; Stroke Trials Unit, Mental Health and Clinical Neuroscience (Bath), University of Nottingham, Nottingham, UK; Advanced Innovation Center for Human Brain Protection (Yongjun Wang), Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
CMAJ. 2024 Feb 11;196(5):E149-E156. doi: 10.1503/cmaj.231262.
Elevated homocysteine levels are associated with increased blood coagulation and platelet activity and may modulate the response to antiplatelet therapies. We aimed to investigate the effects of homocysteine levels on the efficacy and safety of ticagrelor-acetylsalicylic acid (ASA) versus clopidogrel-ASA among patients with minor stroke or transient ischemic attack who carried loss-of-function alleles.
We conducted a post hoc analysis of the CHANCE-2 (The Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial. Participants were randomly assigned to treatment with ticagrelor-ASA or clopidogrel-ASA. We categorized participants into groups with elevated and non-elevated homocysteine levels, based on the median level. The primary efficacy outcome was recurrent stroke within 90-day follow-up. The primary safety outcome was severe or moderate bleeding within 90 days.
A total of 2740 participants were randomly assigned to receive ticagrelor-ASA and 2700 to receive clopidogrel-ASA. Use of ticagrelor-ASA was associated with a reduced risk of recurrent stroke among participants with elevated homocysteine levels (74 [5.3%] v. 119 [8.5%]; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.45-0.81), but not among those with non-elevated levels (86 [6.4%] v. 87 [6.7%]; HR 0.97, 95% CI 0.71-1.32; = 0.04 for interaction). When analyzed as a continuous variable, the benefits of ticagrelor-ASA with regard to recurrent stroke increased as homocysteine levels increased ( = 0.04 for interaction). No significant interaction between homocysteine levels and treatment with regard to severe or moderate bleeding was observed ( = 0.7 for interaction). We found a significant interaction between homocysteine levels and therapy with regard to recurrent stroke in females ( = 0.04 for interaction) but not males.
In comparison with clopidogrel-ASA, ticagrelor-ASA conferred more benefit to patients with elevated homocysteine levels, particularly to female patients, in this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA.
ClinicalTrials.gov, no. NCT04078737.
同型半胱氨酸水平升高与血液凝固和血小板活性增加有关，可能调节抗血小板治疗的反应。我们旨在研究同型半胱氨酸水平对携带功能丧失等位基因的小卒中和短暂性脑缺血发作患者中替格瑞洛-乙酰水杨酸（ASA）与氯吡格雷-ASA 疗效和安全性的影响。
我们对 CHANCE-2（氯吡格雷在急性非致残性脑血管事件高危患者中的应用-2）试验进行了事后分析。参与者被随机分配接受替格瑞洛-ASA 或氯吡格雷-ASA 治疗。我们根据中位数水平将参与者分为同型半胱氨酸水平升高和非升高组。主要疗效终点是 90 天随访期间的复发性卒中。主要安全性终点是 90 天内严重或中度出血。
共有 2740 名参与者被随机分配接受替格瑞洛-ASA 治疗，2700 名接受氯吡格雷-ASA 治疗。同型半胱氨酸水平升高的参与者中，替格瑞洛-ASA 的使用与复发性卒中风险降低相关（74[5.3%]例比 119[8.5%]例；风险比[HR]0.60，95%置信区间[CI]0.45-0.81），但同型半胱氨酸水平非升高的参与者中则不然（86[6.4%]例比 87[6.7%]例；HR 0.97，95%CI 0.71-1.32；交互检验 P=0.04）。当作为连续变量进行分析时，随着同型半胱氨酸水平的升高，替格瑞洛-ASA 降低复发性卒中的获益增加（交互检验 P=0.04）。未观察到同型半胱氨酸水平与治疗严重或中度出血之间存在显著的交互作用（交互检验 P=0.7）。我们发现，在女性患者中，同型半胱氨酸水平与治疗之间与复发性卒中存在显著的交互作用（交互检验 P=0.04），但在男性患者中则不然。
在这项涉及小卒中和 TIA 患者的随机对照试验的二次分析中，与氯吡格雷-ASA 相比，替格瑞洛-ASA 为同型半胱氨酸水平升高的患者，特别是女性患者，带来了更大的益处。
ClinicalTrials.gov，编号 NCT04078737。
