Efficacy of Minocycline in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis of Rodent and Clinical Studies

Zhaofu Sheng, Yang Liu, Hongmin Li, Wei Zheng, Bin Xia, Xin Zhang, V Wee Yong, Mengzhou Xue, Zhaofu Sheng, Yang Liu, Hongmin Li, Wei Zheng, Bin Xia, Xin Zhang, V Wee Yong, Mengzhou Xue

Abstract

Objectives: This study aimed to assess the efficacy of minocycline for the treatment of acute ischemic stroke. Background: While there have been meta-analysis that surveyed the efficacy of minocycline in the treatment of acute stroke, they have some methodological limitations. We performed a new systematic review which was distinct from previous one by adding new outcomes and including new studies. Methods: Document retrieval was executed through PubMed, Cochrane Central Register of Controlled Trials, the Stroke Center, NIH's Clinical Trials, Current Controlled Trials, and the WHO International Clinical Trials Registry Platform Search Portal before Jan 2018. The data meeting the inclusion criteria were extracted. Before meta-analysis, publication bias and heterogeneity of included studies were surveyed. Random and fixed-effects models were employed to calculate pooled estimates and 95% confidence intervals (CIs). Additionally, sensitivity and subgroup analyses were implemented. Result: For clinical studies, 4 trials with 201 patients in the minocycline group, and 195 patients in the control group met the inclusion criteria; 3 were randomized trials. At the end of 90-day follow up or discharge day, results showed that the groups receiving minocycline were superior to the control group, with significant differences in the NIHSS scores (mean difference [MD], -2.75; 95% CI, -4.78, 0.27; p = 0.03) and mRS scores (MD, -0.98; 95% CI, -1.27, -0.69; p < 0.01), but not Barthel Index Score (MD, 9.04; 95% CI, -0.78, 18.07; p = 0.07). For rodent experiments, 14 studies were included. Neurological severity scores (NSS) was significantly improved (MD, -1.38; 95% CI, -1.64, -1.31; p < 0.01) and infarct volume was obviously reduced (Std mean difference [SMD], -2.38; 95% CI, -3.40, -1.36; p < 0.01) in the minocycline group. Heterogeneity among the studies was proved to exist for infarct volume (Chi2 = 116.12, p < 0.01; I2 = 0.89) but not for other variables. Conclusions: Based on the results in our study, minocycline appears as an effective therapeutic option for acute ischemic stroke.

Keywords: clinical study; ischemic stroke; meta-analysis; minocycline; rodent study.

Figures

Figure 1
Figure 1
Flow chart of literature assessment for studies.
Figure 2
Figure 2
Methodological quality assessment for randomized clinical trials. (A) Risk of bias graph: review judgments about each risk of bias item presented as percentages across all included studies. (B) Risk of bias summary: review judgments about each risk of bias item for each included study. “+,” low risk of bias; “–,” high risk of bias; “?,” unclear risk of bias.
Figure 3
Figure 3
Funnel plot assessing publication bias of rodent experimental studies. (A) Neurological Severity Score, NSS. (B) Infarct volume. Vertical lines represent the summary effects; dashed lines denote the 95% CIs.
Figure 4
Figure 4
Forest plot illustrating the meta-analysis of the clinical outcome. (A) National Institutes of Health Stroke Scale, NIHSS. (B) modified Rankin Scale, mRS. (C) Barthel Index, BI.
Figure 5
Figure 5
Forest plot illustrating the meta-analysis of the rodent experimental outcome. (A) Neurological Severity Score, NSS. (B) NSS stratified by administration route. (C) Infarct volume.

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