Impact of remote ischemic postconditioning on acute ischemic stroke in China: a systematic review and meta-analysis of randomized controlled trials

Abstract

Objective: Acute ischemic stroke (AIS) is a significant health burden in China, affecting a sizable portion of the population. Conventional pharmacological treatments frequently fall short of desirable outcomes. Therefore, exploring alternative therapies is crucial. Remote ischemic postconditioning (RIPostC) is a noninvasive and cost-effective adjunctive therapy. This study aimed to investigate the efficacy and safety of RIPostC as an adjunctive therapy for AIS to inform clinical practice.

Methods: A comprehensive search was conducted across the PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, Weipu (VIP), and China Biology Medicine disc (CBM) databases up to October 2023. All included studies underwent bias risk assessment using the Cochrane risk-of-bias assessment tool. The primary outcome measure was the National Institute of Health Stroke Scale (NIHSS), with secondary outcomes including the Barthel index (BI), D-dimer, C-reactive protein (CRP), fibrinogen (FIB), brain-derived neurotrophic factor (BDNF), modified Rankin scale (mRS), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels. The data were analyzed using fixed-effects and random-effects models in Review Manager, with mean differences (MDs) and 95% confidence intervals (CIs) calculated for each outcome. The grading of recommendations, assessment, development, and evaluations (GRADE) approach was used to evaluate the level of evidence for each outcome measure.

Results: This meta-analysis included 38 studies, encompassing 4334 patients. Compared with the control group, the RIPostC group had significantly lower NIHSS scores, serum CRP, D-dimer, IL-6, TNF-α, and FIB levels, and increased BDNF levels. Moreover, it improved the patient's BI and mRS scores. According to the GRADE approach, the quality of evidence for mRS was deemed "moderate," while the NIHSS, BI, and CRP were rated as "low" quality. IL-6, TNF-α, FIB, D-dimer, and BDNF received "very low" quality ratings.

Conclusion: The findings suggest that RIPostC activates endogenous protective mechanisms, providing benefits to patients with AIS.

Fig. 1

Flowchart illustrating the study screening process

Fig. 2

Forest plot of NIHSS in 3-day group

Fig. 3

A Forest plot of NIHSS on 7th day in 7-day group. B Forest plot of NIHSS on 7th day in 7-day group without Zhou et al.’s study. C Forest plot of NIHSS on 14th day in 7-day group

Fig. 4

Forest plot of NIHSS in 10-day group

Fig. 5

A Forest plot of NIHSS on 14th day in 14-day group. B Forest plot of NIHSS on 30th day in 14-day group. C Forest plot of NIHSS on 90th day in 14-day group

Fig. 6

A Forest plot of NIHSS scores on 30th day in 6-month group. B Forest plot of NIHSS scores on 180th day in 6-month group

Fig. 7

A Forest plot of BI on 7th day in 7-day group. B Forest plot of BI on 14th day in 7-day group. C Forest plot of BI on 14th day in 14-day group. D Forest plot of BI on 30th day in 14-day group. E Forest plot of BI on 90th day in 14-day group

Fig. 8

A Forest plot of mRS on 7th day in 7-day group. B Forest plot of mRS on 90th day in 7-day group. C Forest plot of mRS on 90th day in 14-day group

Fig. 9

A Forest plot of IL-6 on 14th day in 14-day group. B Forest plot of IL-6 on 30th day in 6-month group. C Forest plot of TNF-α on 30th day in 6-month group

Fig. 10

A Forest plot of CRP on 30th day in 6-month group. B Forest plot of FIB on 7th day in 7-day group. B Forest plot of D-D on 7th day in 7-day group

Fig. 11

Forest plot of BDNF on 14th day in 14-day group

Fig. 12

Risk-of-bias graph

Fig. 13

Risk-of-bias summary graph