Center for Evidence-Based Medicine, Xuanwu Hospital Capital Medical University, Beijing, China.
Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.
Lancet Neurol. 2022 Dec;21(12):1089-1098. doi: 10.1016/S1474-4422(22)00335-0. Epub 2022 Oct 27.
Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide, and it is associated with a high risk of recurrent stroke with currently recommended treatments. We aimed to evaluate the effect of chronic remote ischaemic conditioning on prevention of ischaemic events in patients with symptomatic ICAS.
The RICA trial is a multicentre, randomised, double-blind, sham-controlled trial at 84 stroke centres in China. Patients aged 40-80 years with ischaemic stroke or transient ischaemic attack attributable to angiographically verified 50-99% stenosis of a major intracranial artery were randomly assigned (1:1), via an interactive web-based system by computer-generated randomisation code, to either remote ischaemic conditioning or sham remote ischaemic conditioning once daily for 12 months and voluntarily thereafter. All investigators and patients were masked to treatment allocation. The primary efficacy endpoint was the time to first occurrence of non-fatal or fatal ischaemic stroke, with survival analysed by the Kaplan-Meier method. Primary and safety analyses were done in the intention-to-treat population. The RICA trial is registered with ClinicalTrials.gov, number NCT02534545.
Between Oct 28, 2015, and Feb 28, 2019, 3033 patients were enrolled and randomly assigned to either remote ischaemic conditioning (n=1517; intervention group) or sham remote ischaemic conditioning (n=1516; sham group). Median follow-up was 3·5 years (IQR 2·7-4·4). A non-fatal or fatal ischaemic stroke occurred in 257 (16·9%) patients in the intervention group compared with 288 (19·0%) patients in sham group. There was no difference in the survival distribution for time to first occurrence of non-fatal or fatal ischaemic stroke (hazard ratio 0·87, 95% CI 0·74-1·03; p=0·12). In the intervention group, 79 (5·2%) patients died from any cause, and in the sham group, 84 (5·5%) patients died from any cause (hazard ratio 0·93, 95% CI 0·68-1·27; p=0·65). No intervention-related serious adverse events were observed.
No evidence was found for a difference between remote ischaemic conditioning and sham remote ischaemic conditioning in lowering the risk of ischaemic stroke in patients with symptomatic ICAS. The benefit of remote ischaemic conditioning might have been diluted by poor compliance. Future studies of remote ischaemic conditioning in this population should address challenges in patients' compliance and assess longer term treatment.
Ministry of Science and Technology China, Beijing Municipal Education Commission, Beijing Municipal Finance Bureau.
For the Chinese translation of the abstract see Supplementary Materials section.
颅内动脉粥样硬化性狭窄（ICAS）是全球范围内最常见的中风病因之一，与目前推荐的治疗方法相关的复发性中风风险较高。我们旨在评估慢性远程缺血预处理对有症状性 ICAS 患者预防缺血事件的效果。
RICA 试验是在中国 84 个卒中中心进行的一项多中心、随机、双盲、假对照试验。年龄在 40-80 岁之间的患者，有缺血性卒中和短暂性脑缺血发作，归因于经血管造影证实的主要颅内动脉 50-99%狭窄，通过基于网络的交互式系统，以 1:1 的比例随机分配（通过计算机生成的随机分配代码）至远程缺血预处理组或假远程缺血预处理组，每天接受一次治疗，持续 12 个月，之后可自愿继续治疗。所有研究者和患者均对治疗分配设盲。主要疗效终点为首次发生非致死性或致死性缺血性卒中的时间，通过 Kaplan-Meier 方法进行生存分析。主要分析和安全性分析均在意向治疗人群中进行。RICA 试验在 ClinicalTrials.gov 注册，编号为 NCT02534545。
2015 年 10 月 28 日至 2019 年 2 月 28 日，共纳入 3033 名患者，并随机分配至远程缺血预处理组（n=1517；干预组）或假远程缺血预处理组（n=1516；假处理组）。中位随访时间为 3.5 年（IQR 2.7-4.4）。干预组 257 名（16.9%）患者发生非致死性或致死性缺血性卒中，而假处理组 288 名（19.0%）患者发生该事件。首次发生非致死性或致死性缺血性卒中的时间的生存分布无差异（风险比 0.87，95%CI 0.74-1.03；p=0.12）。在干预组中，79 名（5.2%）患者因任何原因死亡，而在假处理组中，84 名（5.5%）患者因任何原因死亡（风险比 0.93，95%CI 0.68-1.27；p=0.65）。未观察到与干预相关的严重不良事件。
在有症状性 ICAS 患者中，与假远程缺血预处理相比，远程缺血预处理并未降低缺血性中风的风险。可能由于患者依从性差，远程缺血预处理的获益被削弱。未来在该人群中进行的远程缺血预处理研究应解决患者依从性方面的挑战，并评估更长期的治疗效果。
中国科学技术部、北京市教育委员会、北京市财政局。
