From the Department of Neurology (X.M., A.W., X.T., H.L., Y.Z., X.X., J.J., J.L., Yi.W., X.Z., Z.L., L.L., Y.J., Yo.W.) and Advanced Innovation Center for Human Brain Protection (Yo.W.), Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases (X.M., A.W., X.T., H.L., Y.Z., X.X., J.J., J.L., Yi.W., X.Z., Z.L., L.L., Y.J., Yo.W.), Beijing; Department of Epidemiology and Health Statistics (X.T., Y.Z.), School of Public Health, Capital Medical University, Beijing; Beijing Municipal Key Laboratory of Clinical Epidemiology (X.T.,Y.Z.), China; Department of Neurology (S.C.J.), University of California, San Francisco; and Stroke Trials Unit (P.M.B.), Mental Health & Clinical Neuroscience, University of Nottingham, UK.
Neurology. 2024 Feb 13;102(3):e207809. doi: 10.1212/WNL.0000000000207809. Epub 2024 Jan 5.
The Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that among Chinese patients with minor ischemic stroke or transient ischemic attack (TIA) who were carriers of loss-of-function alleles, dual-antiplatelet therapy with ticagrelor-aspirin reduced the 90-day risk of stroke without increased severe or moderate bleeding compared with clopidogrel-aspirin. However, whether dual-antiplatelet therapy with ticagrelor was superior to clopidogrel beyond the 90 days of follow-up remained unclear. In this study, we reported 1-year follow-up outcomes of the CHANCE-2 trial.
The CHANCE-2 trial is a randomized, double-blind, placebo-controlled trial at 202 centers in China. Patients with a minor stroke or TIA who carried loss-of-function alleles were randomized within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor and placebo clopidogrel or to receive clopidogrel and placebo ticagrelor for 90 days; both groups received aspirin for the first 21 days. After day 90, treatment was as per the choice of the clinician and the patient.
Among 6,412 patients, the proportion of patients on ticagrelor plus aspirin, clopidogrel plus aspirin, ticagrelor alone, clopidogrel alone, aspirin alone, other antiplatelet, and no antiplatelet beyond month 3 to 1 year was 0.09%, 1.56%, 0.13%, 2.66%, 73.65%, 0.78%, and 21.13% in the ticagrelor-aspirin group and 0.03%, 1.63%, 0.19%, 2.60%, 72.83%, 0.66%, and 22.06% in the clopidogrel-aspirin group, respectively. The primary outcome of new stroke occurred in 252 patients (7.91%) in the ticagrelor-aspirin group and 310 patients (9.73%) in the clopidogrel-aspirin group by 1 year of follow-up (hazard ratio 0.80; 95% CI 0.68-0.95; = 0.007); new stroke beyond 3 months to 1 year occurred in 61 patients (2.07%) and 67 patients (2.32%) ( = 0.48), respectively. Primary safety outcome of severe or moderate bleeding occurred in 17 patients (0.53%) in the ticagrelor-aspirin group and 20 patients (0.63%) in the clopidogrel-aspirin group ( = 0.61).
For loss-of-function allele carriers, early dual-antiplatelet therapy with ticagrelor is superior to clopidogrel at 1 year in reducing recurrent stroke.
URL: clinicaltrials.gov. Unique identifier: NCT04078737.
This study provides Class II evidence that for patients with minor stroke or TIA with TIACYP2C19 loss-of-function, ticagrelor plus aspirin for 21 days is superior to clopidogrel plus aspirin in reducing the 1-year risk of recurrent stroke.
在 Ticagrelor 或氯吡格雷联合阿司匹林用于急性非致残性脑血管事件高危患者的 Ticagrelor 或 Clopidogrel 与阿司匹林在高风险患者中的应用 II（CHANCE-2）试验中，研究结果表明在中国患有小卒中和 TIA 且携带功能丧失等位基因的患者中，与氯吡格雷联合阿司匹林相比，替格瑞洛联合阿司匹林双联抗血小板治疗可降低 90 天内的卒中风险，且不会增加严重或中度出血。然而，替格瑞洛双联抗血小板治疗是否优于氯吡格雷超过 90 天的随访期仍不清楚。本研究报告了 CHANCE-2 试验的 1 年随访结果。
CHANCE-2 试验是在中国 202 个中心进行的一项随机、双盲、安慰剂对照试验。在症状发作后 24 小时内，携带功能丧失等位基因的小卒中和 TIA 患者，按照 1:1 的比例随机接受替格瑞洛和安慰剂氯吡格雷或氯吡格雷和安慰剂替格瑞洛治疗 90 天；两组均在前 21 天使用阿司匹林。第 90 天后，治疗方案根据医生和患者的选择进行。
在 6412 例患者中，替格瑞洛联合阿司匹林组、氯吡格雷联合阿司匹林组、替格瑞洛单药组、氯吡格雷单药组、阿司匹林单药组、其他抗血小板组和无抗血小板组在第 3 至 1 年的比例分别为 0.09%、1.56%、0.13%、2.66%、73.65%、0.78%和 21.13%，氯吡格雷联合阿司匹林组分别为 0.03%、1.63%、0.19%、2.60%、72.83%、0.66%和 22.06%。替格瑞洛联合阿司匹林组新发生卒中的主要终点在 1 年随访中为 252 例（7.91%），氯吡格雷联合阿司匹林组为 310 例（9.73%）（风险比 0.80；95%置信区间 0.68-0.95；P=0.007）；替格瑞洛联合阿司匹林组新发生卒中超过 3 个月至 1 年为 61 例（2.07%），氯吡格雷联合阿司匹林组为 67 例（2.32%）（P=0.48）。严重或中度出血的主要安全性结局在替格瑞洛联合阿司匹林组为 17 例（0.53%），氯吡格雷联合阿司匹林组为 20 例（0.63%）（P=0.61）。
对于功能丧失等位基因携带者，早期替格瑞洛双联抗血小板治疗在 1 年时可降低复发性卒中的风险，优于氯吡格雷。
网址：clinicaltrials.gov。唯一标识符：NCT04078737。
本研究提供了 II 级证据，表明对于患有小卒中和 TIA 且携带 TIACYP2C19 功能丧失的患者，替格瑞洛加阿司匹林治疗 21 天可降低复发性卒中的 1 年风险。
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