Qiao Yue, Hui Wen, Li Sijie, Ding Yuchuan, Ji Xunming, Zhao Wenbo
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Department of Science and Technology, West China Hospital, Sichuan University, Chengdu, China.
Cochrane Database Syst Rev. 2025 Sep 24;9(9):CD012503. doi: 10.1002/14651858.CD012503.pub3.
Remote ischaemic conditioning (RIC) has been innovatively utilised as a neuroprotective method in the prevention and treatment of stroke. RIC typically involves transiently restricting then restoring blood flow to limbs. The current evidence, as derived from various studies, indicates some beneficial effects of RIC, but also highlights the need for further investigation due to the presence of uncertainties and variations in study designs and outcomes.
To evaluate the benefits and harms of remote ischaemic conditioning in preventing and treating ischaemic stroke compared to sham or standard treatments.
We searched CENTRAL, MEDLINE, Embase, Web of Science, three Chinese databases, five trials registers, and conference proceedings, together with reference checking and citation searching. The latest search date was 11 March 2025.
We included randomised controlled trials (RCTs) comparing RIC with sham RIC or standard medical management, over any length of follow-up, in people with ischaemic stroke.
Our critical outcomes were mortality, recurrence of ischaemic stroke, and excellent functional outcome (Modified Rankin Scale (mRS) score 0-1). Our important outcomes were treatment-related adverse events, functional independence (mRS score 0-2), haemorrhagic stroke, stroke severity, improvement in neurological impairment, and cardiovascular events.
We assessed risk of bias using the original Cochrane risk of bias tool (RoB 1).
We used standard Cochrane methodology. We synthesised results for each outcome through meta-analysis where possible, using either the inverse variance or Mantel-Haenszel method with a random-effects model. We used the GRADE approach to assess the certainty of the evidence.
This review included 20 RCTs with 7687 participants, though we analysed two publications from a single RCT as two separate studies. Sixteen RCTs with 7166 participants were new to this update. The studies were conducted in China, Denmark, the UK, the Netherlands, France, and Romania, and were published between 2012 and 2025. Fourteen studies investigated short-duration RIC, four evaluated medium-duration RIC, and three investigated long-duration RIC. Because studies reported the timing of RIC application after stroke onset in various ways, we made assumptions to combine data, which may have introduced extra heterogeneity or bias and affected the certainty of our conclusions regarding the optimal RIC application timing. We also identified 21 ongoing trials.
The evidence suggests that RIC compared to non-RIC probably results in a slight reduction in the risk of ischaemic stroke recurrence (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.73 to 0.98; 16 RCTs, 6828 participants; moderate-certainty evidence) and probably has no little to no effect on mortality risk (RR 0.91, 95% CI 0.74 to 1.12; 15 RCTs, 7203 participants; moderate-certainty evidence). RIC may result in a slight increase in excellent functional outcome (mRS 0-1) at 90 days (RR 1.14, 95% CI 1.01 to 1.28; 10 RCTs, 3091 participants; low-certainty evidence), but probably has little to no effect on functional independence (mRS 0-2) at 90 days (RR 1.03, 95% CI 0.97 to 1.09; 11 RCTs, 3979 participants; moderate-certainty evidence). Studies measured improvement in neurological impairment on the National Institutes of Health Stroke Scale (NIHSS), and the pooled evidence suggests a slight improvement with RIC, but the evidence is very uncertain (mean difference (MD) -0.97, 95% CI -1.74 to -0.21; 12 RCTs, 1341 participants; very low-certainty evidence). RIC compared to non-RIC may result in little to no difference in the risk of intracerebral haemorrhagic events (RR 0.96, 95% CI 0.59 to 1.57; 12 RCTs, 5908 participants; low-certainty evidence) and cardiovascular events (RR 0.85, 95% CI 0.68 to 1.08; 8 RCTs, 4357 participants; low-certainty evidence), but may result in a large increase in treatment-related adverse events (RR 6.13, 95% CI 2.85 to 13.18; 17 RCTs, 7274 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that RIC compared to non-RIC probably reduces recurrence of ischaemic stroke slightly, and low-certainty evidence that RIC may result in a slight increase in excellent functional outcome (mRS 0-1). Evidence for improvement in NIHSS scores is very uncertain due to risk of bias and imprecision. RIC demonstrated an acceptable harm profile with no increase in intracerebral haemorrhage or mortality; however, treatment-related adverse events were more common. The certainty of evidence was limited by high risk of bias for blinding in most studies, incomplete outcome data in some studies, and imprecision in several outcomes. However, the generalisability of these findings may be limited because 79.3% of participants were from China, highlighting the need for further studies in diverse populations to confirm the results. The optimal timing, duration, and method of RIC administration require further investigation through large, high-quality randomised trials with standardised protocols to establish definitive evidence for clinical practice. This updated analysis includes 16 new RCTs, and these findings highlight the need for ongoing research and careful consideration of study design and methodology in future investigations.
This Cochrane review was supported by the National Natural Science Foundation of China (82422024) and the Beijing Natural Science Foundation (JQ22020).
Protocol: Cochrane Library via DOI 10.1002/14651858.CD012503. Original review, Cochrane Library via 10.1002/14651858.CD012503.pub2.
远程缺血预处理（RIC）已被创新性地用作预防和治疗中风的神经保护方法。RIC通常包括短暂限制然后恢复肢体的血流。来自各种研究的现有证据表明了RIC的一些有益效果，但也强调由于研究设计和结果存在不确定性和差异，需要进一步调查。
评估与假手术或标准治疗相比，远程缺血预处理在预防和治疗缺血性中风中的益处和危害。
我们检索了Cochrane中心对照试验注册库、MEDLINE、Embase、Web of Science、三个中文数据库、五个试验注册库和会议论文集，并进行了参考文献核对和引文检索。最新检索日期为2025年3月11日。
我们纳入了比较RIC与假RIC或标准药物治疗的随机对照试验（RCT），随访时间不限，研究对象为缺血性中风患者。
我们的关键结局指标是死亡率、缺血性中风复发率和良好功能结局（改良Rankin量表（mRS）评分0 - 1）。我们的重要结局指标是治疗相关不良事件、功能独立性（mRS评分0 - 2）、出血性中风、中风严重程度、神经功能缺损改善情况和心血管事件。
我们使用原始的Cochrane偏倚风险工具（RoB 1）评估偏倚风险。
我们采用标准的Cochrane方法。我们尽可能通过荟萃分析对每个结局指标的结果进行合成，使用逆方差法或Mantel - Haenszel法，并采用随机效应模型。我们使用GRADE方法评估证据的确定性。
本综述纳入了20项RCT，共7687名参与者，不过我们将来自同一RCT的两篇出版物作为两项独立研究进行分析。本次更新新增了16项RCT，共7166名参与者。这些研究在中国、丹麦、英国、荷兰、法国和罗马尼亚进行，发表时间在2012年至2025年之间。14项研究调查了短期RIC，4项评估了中期RIC，3项调查了长期RIC。由于研究报告中风发作后RIC应用时间的方式各不相同，我们进行了假设以合并数据，这可能引入了额外的异质性或偏倚，并影响了我们关于最佳RIC应用时间结论的确定性。我们还确定了21项正在进行的试验。
证据表明，与非RIC相比，RIC可能会使缺血性中风复发风险略有降低（风险比（RR）0.84，95%置信区间（CI）0.73至0.98；16项RCT，6828名参与者；中等确定性证据），并且可能对死亡风险几乎没有影响（RR 0.91，95% CI 0.74至1.12；15项RCT，7203名参与者；中等确定性证据）。RIC可能会使90天时良好功能结局（mRS 0 - 1）略有增加（RR 1.14，95% CI 1.01至1.28；10项RCT，3091名参与者；低确定性证据），但可能对90天时的功能独立性（mRS 0 - 2）几乎没有影响（RR 1.03，95% CI 0.97至1.09；11项RCT，3979名参与者；中等确定性证据）。研究测量了国立卫生研究院卒中量表（NIHSS）上神经功能缺损的改善情况，汇总证据表明RIC有轻微改善，但证据非常不确定（平均差（MD） - 0.97，95% CI - 1.74至 - 0.21；12项RCT，1341名参与者；极低确定性证据）。与非RIC相比，RIC可能在脑内出血事件风险（RR 0.96，95% CI 0.59至1.57；12项RCT，5908名参与者；低确定性证据）和心血管事件风险（RR 0.85，95% CI 0.68至1.08；8项RCT，4357名参与者；低确定性证据）方面几乎没有差异，但可能会使治疗相关不良事件大幅增加（RR 6.13，95% CI 2.85至13.18；17项RCT，7274名参与者；低确定性证据）。
有中等确定性证据表明，与非RIC相比，RIC可能会略微降低缺血性中风的复发率，低确定性证据表明RIC可能会使良好功能结局（mRS 0 - 1）略有增加。由于存在偏倚风险和不精确性，NIHSS评分改善的证据非常不确定。RIC显示出可接受的危害特征，脑出血或死亡率没有增加；然而，治疗相关不良事件更为常见。证据的确定性受到大多数研究中高偏倚风险、一些研究中不完整的结局数据以及几个结局指标的不精确性的限制。然而，这些发现的普遍性可能有限，因为79.3%的参与者来自中国，这突出了需要在不同人群中进行进一步研究以证实结果。RIC给药的最佳时间、持续时间和方法需要通过大型、高质量的随机试验和标准化方案进行进一步研究，以建立临床实践的确凿证据。本次更新分析包括16项新的RCT，这些发现突出了持续研究的必要性以及未来研究中对研究设计和方法的仔细考虑。
本Cochrane综述得到了中国国家自然科学基金（82422024）和北京市自然科学基金（JQ22020）的支持。
方案：通过DOI 10.1002/14651858.CD012503在Cochrane图书馆注册。原始综述，通过10.1002/14651858.CD012503.pub2在Cochrane图书馆注册。
