Key messages
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Remote ischaemic conditioning (briefly restricting then restoring blood flow) likely reduces the risk of another stroke happening and may help people recover brain function and daily abilities more effectively than sham or standard treatment. Remote ischaemic conditioning is considered a low-cost, accessible, and non-invasive treatment option, though it may have some unwanted effects.
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Most of the studies included in this review had few participants and took place in China. We need larger and better-designed studies to draw definitive conclusions about the long-term benefits and harms of remote ischaemic conditioning.
What is ischaemic stroke?
Ischaemic stroke is the most common type of stroke. It occurs when a blood clot blocks an artery that supplies blood to the brain. This blockage cuts off the supply of oxygen and nutrients to a part of the brain. Without this blood supply, brain cells in that area are damaged and begin to die.
What is remote ischaemic conditioning?
Remote ischaemic conditioning (RIC) involves briefly and repeatedly restricting and then restoring blood flow in a limb (an arm or leg) with a blood pressure cuff. The goal is to "condition" the limb and trigger the body's natural defences to protect other organs.
What are the benefits of using remote ischaemic conditioning in people with ischaemic stroke?
Studies have found that for people who have had a stroke and are receiving standard medical care, adding RIC can reduce the amount of brain tissue damaged by the stroke, improve recovery of everyday functions, help prevent another stroke from happening, and reduce problems with memory and thinking.
What did we want to find out?
We wanted to evaluate the benefits and harms of RIC in people who have had an ischaemic stroke and are undergoing various treatments, including standard medical therapy, intravenous thrombolysis (a clot-dissolving treatment), or mechanical thrombectomy (a procedure to remove clots). Specifically, we wanted to know if RIC was better than sham or standard treatment for improving:
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the risk of dying;
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the risk of having another stroke;
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the likelihood of an excellent recovery (a score on the Modified Rankin Scale (mRS) of 0 to 1);
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the likelihood of being able to live independently (mRS score of 0 to 2);
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the risk of a brain bleed;
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brain function issues;
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the risk of major heart problems.
We also wanted to know if RIC has unwanted effects.
What did we do?
We searched for studies that compared the benefits and harms of remote ischaemic conditioning in people with ischaemic stroke. We then compared and summarised the study results and rated our confidence in the evidence based on factors such as study methods and sample sizes.
What did we find?
We found 21 studies with 7687 people. The studies took place in China, Denmark, France, the UK, and Romania, and were published between 2012 and 2025.
Sixteen studies including 6828 participants suggested that RIC compared to sham or no treatment probably leads to a slight reduction in the risk of having another stroke. About half the studies measured participants' level of independence using the mRS and measured change in brain function issues using the National Institutes of Health Stroke Scale (NIHSS). RIC might lead to a slight increase in the number of people achieving an excellent recovery, but may have little or no effect on the number of people being able to live independently. In addition, RIC might result in a slight improvement in brain function issues, but the evidence is very uncertain. There may be little or no difference between RIC and sham or standard treatment in the risk of a brain bleed and major heart problems, and RIC probably does not increase the risk of death. However, RIC may have unwanted effects such as arm pain, redness, or swelling.
We also identified 21 ongoing studies that we plan to add to the next version of our review.
What are the limitations of the evidence?
Our confidence in the evidence is moderate to very low for several reasons. Most studies had few participants, and more than half of studies were done in China, which means the results of our review may not apply to people in other parts of the world. Some studies included people who received clot-dissolving treatment (thrombolysis) and people who did not, and we could not separate the results for these two groups. This mix of patients may have affected our overall analysis. Finally, we did not separate the results in our analysis based on the type of comparison group used (sham or standard treatment). This means it is difficult to know if the treatment effect we found was influenced by the type of comparison.
How up to date is this evidence?
The review is current until 11 March 2025.
Pročitajte cijeli sažetak
Remote ischaemic conditioning (RIC) has been developed as a neuroprotective strategy to prevent and treat ischaemic stroke. It usually involves restricting blood flow to limbs and then releasing the ischaemic blood to promote a neuroprotective effect. Preclinical studies have suggested that RIC may have beneficial effects in ischaemic stroke patients and those at risk of ischaemic stroke. However, existing evidence is insufficient to demonstrate the efficacy and safety of RIC in preventing and treating ischaemic stroke.
Ciljevi
To evaluate the benefits and harms of remote ischaemic conditioning in preventing and treating ischaemic stroke compared to sham or standard treatments.
Metode pretraživanja
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.
Kriteriji odabira
We included randomised controlled trials (RCTs) comparing RIC with sham RIC or medical management in people with ischaemic stroke or at risk of ischaemic stroke.
Prikupljanje podataka i obrada
Two review authors independently selected studies, assessed trial quality and risk of bias, and extracted data. We used the GRADE approach to assess the quality of the evidence.
Glavni rezultati
We included seven trials, involving 735 participants, in this review. We analysed the effects of RIC on preventing and treating ischaemic stroke respectively.
We evaluated risk of bias and judged it to be low for generation of allocation sequence in six studies and unclear in one study; unclear for allocation concealment in four studies and low in three studies; high for incomplete outcome data (attrition bias) in five studies and low in two studies; high for blinding in three studies and low in four studies; low for selective reporting; and high for other sources of bias in six studies and low in one study.
We included three trials (involving 371 participants) in the analysis of the effects of RIC on ischaemic stroke prevention. In people with symptomatic intracerebral artery stenosis, recurrent stroke was significantly reduced by RIC (risk ratio (RR) 0.32, 95% confidence interval (CI) 0.12 to 0.83; 2 trials, 182 participants, low-quality evidence). In people with carotid stenosis undergoing carotid stenting, there was no significant difference in the incidence of ischaemic stroke between participants treated with RIC and non-RIC (RR 0.22, 95% CI 0.01 to 4.03; 1 trial, 189 participants, low-quality evidence); however the stroke severity (assessed by infarct volume) was significantly lower in participants treated with RIC (mean difference (MD) -0.17 mL, 95% CI -0.23 to -0.11; 1 trial, 189 participants, low-quality evidence). Adverse events associated with RIC were significantly higher in participants treated with RIC (RR 10.91; 95% CI 2.01 to 59.28; 3 trials, 371 participants, low-quality evidence), but no severe adverse event was attributable to RIC treatment. No participants experienced death or cardiovascular events during the period of the studies; and no trial reported haemorrhagic stroke or improvement in neurological, phycological or cognitive impairment.
We included four trials (involving 364 participants) in the analysis of the effects of RIC on ischaemic stroke treatment. In acute ischaemic stroke, for people receiving intravenous thrombolysis, the rate of death or dependency was significantly increased by RIC treatment compared with non-RIC treatment (RR 2.34; 95% 1.19 to 4.61; 1 trial, 285 participants, low-quality evidence). In people with acute ischaemic stroke, there was no significant difference between RIC and non-RIC for reducing stroke severity as assessed by the National Institutes of Health Stroke Scale score and the final infarct volume (standardised mean difference (SMD) -0.24 mL, 95% CI -1.02 to 0.54; 2 trials, 175 participants, very low quality evidence). There was no significant difference between RIC and non-RIC for improving the psychological impairment (SMD -0.37 points, 95% CI -1.15 to 0.41; 1 trial, 26 participants, very low quality evidence) and the cognitive impairment (SMD -0.26 points; 95% CI -0.72 to 0.21; 3 trials, 79 participants, low-quality evidence) in people with acute ischaemic stroke and cerebral small vessel disease. No trial reported ischaemic stroke, recurrent ischaemic stroke, improvement in neurological impairment, hemorrhagic stroke, cardiovascular events, and RIC associated adverse events.
Zaključak autora
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.
Funding
This Cochrane review was supported by the National Natural Science Foundation of China (82422024) and the Beijing Natural Science Foundation (JQ22020).
Registration
Protocol: Cochrane Library via DOI 10.1002/14651858.CD012503.
Original review, Cochrane Library via 10.1002/14651858.CD012503.pub2.
