Nash Philip S, Dehbi Hakim-Moulay, Ahmed Norin, Arram Liz, Best Jonathan G, Balogun Maryam, Bennett Kate, Bordea Ekaterina, Caverly Emilia, Chau Marisa, Cohen Hannah, Cullen Mairead, Doré Caroline J, Engelter Stefan T, Fenner Robert, Ford Gary A, Gill Aneet, Hunter Rachael, James Martin, Jayanthi Archana, Lip Gregory Y H, Massingham Sue, Murray Macey L, Mazurczak Iwona, Ndoutoumou Amalia, Norrving Bo, Philip Jenny, Sims Hannah, Sprigg Nikola, Vanniyasingam Tishok, Freemantle Nick, Wheeler David C, Werring David J
Department of Brain Repair and Rehabilitation, Stroke Research Centre, University College London Queen Square Institute of Neurology, United Kingdom (P.S.N., L.A., J.G.B., S.M., D.J.W.).
Comprehensive Clinical Trials Unit, Institute of Clinical Trials and Methodology (H.-M.D., N.A., M.B., K.B., E.B., E.C., M. Chau, M. Cullen, C.J.D., R.F., A.G., R.H., A.J., I.M., A.N., J.P., H.S., T.V., N.F.).
Stroke. 2025 Aug;56(8):1970-1979. doi: 10.1161/STROKEAHA.125.051457. Epub 2025 May 22.
Patients with chronic kidney disease (CKD) are at increased risk of ischemic stroke (IS) and intracerebral hemorrhage, so the safety and efficacy of early direct oral anticoagulant (DOAC) initiation in those with CKD are of clinical relevance.
OPTIMAS (Optimal Timing of Anticoagulation After Acute Ischemic Stroke With Atrial Fibrillation) was a multicenter, randomized, parallel-group, open-label trial with blinded outcome assessment, recruiting patients with IS and atrial fibrillation from 100 UK hospitals between 2019 and 2024. Participants were randomized 1:1, stratified by stroke severity, to early (within 4 days of onset) or delayed (at days 7-14) DOAC initiation. CKD was defined as a past medical history of known CKD, collected according to trial protocol as part of the case report form. For this prespecified subgroup analysis, the trial cohorts were classified according to the presence or absence of CKD. Whether CKD modified the treatment effect of early DOAC initiation was determined by fitting mixed effects logistic regression models with interaction terms between CKD and treatment group. The primary outcome was a composite outcome of recurrent IS, symptomatic intracranial hemorrhage, and systemic arterial embolism. Key secondary outcomes included the individual components of the primary outcome and all-cause mortality.
We included 3601 patients (mean age, 78±10 years; 45% female), 543 with CKD. There were 116 primary outcome events: 97 (3.2%) in the normal kidney function group and 19 (3.5%) in the CKD group. There was no difference between early and delayed DOAC initiation for the primary outcome in either the normal kidney function group (odds ratio, 1.01 [95% CI, 0.67-1.51]) or the CKD group (odds ratio, 0.90 [95% CI, 0.36-2.25]; =0.822). Similarly, for the secondary outcomes, we detected no modification of the treatment effect according to CKD ( values of 0.637, 0.386, and 0.107 for IS, symptomatic intracranial hemorrhage, and all-cause mortality, respectively).
Our findings suggest that CKD does not modify the effects of early versus delayed DOAC initiation after acute IS. Based on these results, early DOAC initiation should not be withheld in patients with CKD.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03759938.
慢性肾脏病（CKD）患者发生缺血性卒中（IS）和脑出血的风险增加，因此CKD患者早期启动直接口服抗凝剂（DOAC）的安全性和有效性具有临床意义。
OPTIMAS（急性缺血性卒中合并心房颤动后抗凝的最佳时机）是一项多中心、随机、平行组、开放标签试验，采用盲法评估结局，于2019年至2024年从英国100家医院招募IS合并心房颤动的患者。参与者按1:1随机分组，根据卒中严重程度分层，分为早期（发病4天内）或延迟（第7 - 14天）启动DOAC。CKD定义为已知CKD的既往病史，根据试验方案作为病例报告表的一部分进行收集。对于这项预先指定的亚组分析，试验队列根据是否存在CKD进行分类。通过拟合CKD与治疗组之间具有交互项的混合效应逻辑回归模型，确定CKD是否改变早期DOAC启动的治疗效果。主要结局是复发性IS、症状性颅内出血和全身性动脉栓塞的复合结局。关键次要结局包括主要结局的各个组成部分和全因死亡率。
我们纳入了3601例患者（平均年龄78±10岁；45%为女性），其中543例患有CKD。共有116例主要结局事件：肾功能正常组97例（3.2%），CKD组19例（3.5%）。在肾功能正常组（比值比，1.01 [95%CI，0.67 - 1.51]）或CKD组（比值比，0.90 [95%CI，0.36 - 2.25]；P = 0.822）中，早期和延迟启动DOAC对于主要结局均无差异。同样，对于次要结局，我们未检测到根据CKD对治疗效果的改变（IS、症状性颅内出血和全因死亡率的P值分别为0.637、0.386和0.107）。
我们的研究结果表明，CKD不会改变急性IS后早期与延迟启动DOAC的效果。基于这些结果，CKD患者不应延迟早期DOAC启动。
