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Meta-Analysis
. 2018 Jul 5;7(7):CD012503.
doi: 10.1002/14651858.CD012503.pub2.

Remote ischaemic conditioning for preventing and treating ischaemic stroke

Wenbo Zhao  1 , Jing Zhang, Mordechai G Sadowsky, Ran Meng, Yuchuan Ding, Xunming Ji
Affiliations
Meta-Analysis

Remote ischaemic conditioning for preventing and treating ischaemic stroke

Wenbo Zhao et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

Objectives: To assess the benefits and harms of RIC for preventing ischaemic stroke and for treating people with ischaemic stroke and those at risk for ischaemic stroke.

Search methods: We searched the Cochrane Stroke Group Trials Register (16 January 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 12) in the Cochrane Library (January 2018), MEDLINE Ovid (1946 to January 2018), Embase Ovid (1974 to January 2018), Web of Science Core Collection (1950 to January 2018) and three Chinese databases (January 2018). We also searched four ongoing trials registers, reference lists, and conference proceedings.

Selection criteria: 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.

Data collection and analysis: 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.

Main results: 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.

Authors' conclusions: We found low-quality evidence that RIC may reduce the risk of recurrent stroke in participants with intracerebral artery stenosis and reduce stroke severity in participants undergoing carotid stenting, but it may increase death or dependence in participants with acute ischaemic stroke who are undergoing intravenous thrombolysis. However, there is considerable uncertainty about these conclusions because of the small number of studies and low quality of the evidence.

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Conflict of interest statement

Wenbo Zhao: none known. Jing Zhang: none known. Mordechai G Sadowsky: none known. Ran Meng: none known. Yuchuan Ding: none known. Xunming Ji: is one of the inventors of the electric auto‐control device that induces remote ischaemic conditioning. This device has been used in many studies, including the ones mentioned in this review. There is no conflict of interest in the conduct of this review. The ownership of the patent belongs to Xuanwu Hospital, Capital Medical University. Dr Ji does not participate in any commercial activities or profits related to the device.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 RIC versus non‐RIC for preventing ischaemic stroke, Outcome 1 Ischaemic stroke or recurrent ischaemic stroke at completion of follow‐up.
1.2
1.2. Analysis
Comparison 1 RIC versus non‐RIC for preventing ischaemic stroke, Outcome 2 Death or dependency at completion of follow‐up.
1.3
1.3. Analysis
Comparison 1 RIC versus non‐RIC for preventing ischaemic stroke, Outcome 3 Stroke severity.
1.6
1.6. Analysis
Comparison 1 RIC versus non‐RIC for preventing ischaemic stroke, Outcome 6 Cardiovascular events.
1.8
1.8. Analysis
Comparison 1 RIC versus non‐RIC for preventing ischaemic stroke, Outcome 8 Adverse events associated with RIC treatment.
2.2
2.2. Analysis
Comparison 2 RIC versus non‐RIC treating ischaemic stroke, Outcome 2 Death or dependency at the completion of follow up.
2.3
2.3. Analysis
Comparison 2 RIC versus non‐RIC treating ischaemic stroke, Outcome 3 Stroke severity.
2.5
2.5. Analysis
Comparison 2 RIC versus non‐RIC treating ischaemic stroke, Outcome 5 Improvement in psychological and cognitive impairment at completion of follow‐up.
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NCT02169739 {unpublished data only}
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References to other published versions of this review

Zhao 2017
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