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Meta-Analysis
. 2024 Apr 9;102(7):e207983.
doi: 10.1212/WNL.0000000000207983. Epub 2024 Mar 8.

Remote Ischemic Conditioning With Medical Management or Reperfusion Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Qi Li  1 , Jinxiu Guo  1 , Hui-Sheng Chen  1 , Rolf Ankerlund Blauenfeldt  1 , David C Hess  1 , Fernando Pico  1 , Pooja Khatri  1 , Bruce C V Campbell  1 , Xinggang Feng  1 , Mohamad Abdalkader  1 , Jeffrey L Saver  1 , Raul G Nogueira  1 , Bingwu Jiang  1 , Bing Li  1 , Min Yang  1 , Hongfei Sang  1 , Qingwu Yang  1 , Zhongming Qiu  1 , Yi Dai  1 , Thanh N Nguyen  1
Affiliations
Meta-Analysis

Remote Ischemic Conditioning With Medical Management or Reperfusion Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Qi Li et al. Neurology. .

Abstract

Background and objectives: Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke are controversial. With the publication of several randomized controlled trials (RCTs) and the recent results of the RESIST trial, it may be possible to identify the patient population that may (or may not) benefit from RIC. This systematic review and meta-analysis aims to evaluate the effectiveness and safety of RIC in patients with ischemic stroke receiving different treatments by pooling data of all randomized controlled studies to date.

Methods: We searched the PubMed, Embase, Cochrane, Elsevier, and Web of Science databases to obtain articles in all languages from inception until May 25, 2023. The primary outcome was the modified Rankin Scale (mRS) score at the specified endpoint time in the trial. The secondary outcomes were change in NIH Stroke Scale (NIHSS) and recurrence of stroke events. The safety outcomes were cardiovascular events, cerebral hemorrhage, and mortality. The quality of articles was evaluated through the Cochrane risk assessment tool. This study was registered in PROSPERO (CRD42023430073).

Results: There were 7,657 patients from 22 RCTs included. Compared with the control group, patients who received RIC did not have improved mRS functional outcomes, regardless of whether they received medical management, reperfusion therapy with intravenous thrombolysis (IVT), or mechanical thrombectomy (MT). In the medical management group, patients who received RIC had decreased incidence of stroke recurrence (risk ratio 0.63, 95% CI 0.43-0.92, p = 0.02) and lower follow-up NIHSS score by 1.72 points compared with the control group (p < 0.00001). There was no increased risk of adverse events including death or cerebral hemorrhage in the IVT or medical management group.

Discussion: In patients with ischemic stroke who are not eligible for reperfusion therapy, RIC did not affect mRS functional outcomes but significantly improved the NIHSS score at the follow-up endpoint and reduced stroke recurrence, without increasing the risk of cerebral hemorrhage or death. In patients who received IVT or MT, the benefit of RIC was not observed.

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Conflict of interest statement

R.A. Blauenfeldt reported receiving grants 1R01NS112511-01A1 from the National Institutes of Health and lecture fees from Bayer and Novo Nordisk outside the submitted work. P. Khatri discloses Cerenovus (PI of an unrestricted grant for investigator-initiated clinical trial, ENDOLOW); Bayer (National Leader of clinical trial, PACIFIC-Stroke); consulting for Lumosa and Basking Biosciences (for scientific advisory board participation); Shionogi (one-time consultant). T.N. Nguyen discloses advisory board with Idorsia and Brainomix, and is Associate Editor of Stroke. R.G. Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; and grants from Cerenovus and Stryker. F. Pico reported receiving grants from the French Ministry of Health and serving as principal investigator of the RESCUE BRAIN trial. J.L. Saver received contracts from Medtronic, Abbott, NeuroVasc, PhillipsMedical, Bayer, Biogen, Roche, BrainsGate, BrainQ, and Occlutech and stock options from Rapid Medical and QuantalX for service on clinical trial steering committees and Data and Security Monitoring Committees and advising on rigorous study design and conduct. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. PRISMA Flow Diagram
PRISMA = Preferred Reporting Items for Systematic Review and Meta-analysis.
Figure 2
Figure 2. Forest Plots for Patients in the Medical Management Group Treated With RIC or Control
Forest plots for patients in the medical management group treated with RIC or control reporting (A) excellent outcome (mRS 0–1), (B) functional independence (mRS 0–2), (c) NIHSS on follow-up (ranging between 10 days and 12 months), and (D) stroke recurrence. mRS = modified Rankin Scale; NIHSS = NIH Stroke Scale; RIC = remote ischemic conditioning; RCT = randomized controlled trial.
Figure 3
Figure 3. Forest Plots of Patients Who Received IVT Treated With RIC or Control
Forest plots of patients who received IVT treated with RIC or control reporting (A) excellent outcome (mRS 0–1), (B) functional independence (mRS 0–2), and (C) stroke recurrence. IVT = IV thrombolysis; mRS = modified Rankin Scale; RIC = remote ischemic conditioning; RCT = randomized controlled trial.
Figure 4
Figure 4. Forest Plots of Patients Who Received Mechanical Thrombectomy Treated With RIC or Control
Forest plots of patients who received mechanical thrombectomy treated with RIC or control reporting (A) excellent outcome (mRS 0–1) and (B) functional independence (mRS 0–2). mRS = modified Rankin Scale; RIC = remote ischemic conditioning; RCT = randomized controlled trial.
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