Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials
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Various randomized-controlled clinical trials (RCTs) have investigated the neuroprotective role of minocycline in acute ischemic stroke (AIS) or acute intracerebral hemorrhage (ICH) patients. We sought to consolidate and investigate the efficacy and safety of minocycline in patients with acute stroke.
Literature search spanned through November 30, 2017 across major databases to identify all RCTs that reported following efficacy outcomes among acute stroke patients treated with minocycline vs. placebo: National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS) scores. Additional safety, neuroimaging and biochemical endpoints were extracted. We pooled mean differences (MD) and risk ratios (RR) from RCTs using random-effects models.
We identified 7 RCTs comprising a total of 426 patients. Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs. In pooled analysis, minocycline demonstrated a favorable trend towards 3-month functional independence (mRS-scores of 0–2) (RR = 1.31; 95% CI 0.98–1.74, p = 0.06) and 3-month BI (MD = 6.92; 95% CI − 0.92, 14.75; p = 0.08). In AIS subgroup, minocycline was associated with higher rates of 3-month mRS-scores of 0–2 (RR = 1.59; 95% CI 1.19–2.12, p = 0.002; I2 = 58%) and 3-month BI (MD = 12.37; 95% CI 5.60, 19.14, p = 0.0003; I2 = 47%), whereas reduced the 3-month NIHSS (MD − 2.84; 95% CI − 5.55, − 0.13; p = 0.04; I2 = 86%). Minocycline administration was not associated with an increased risk of mortality, recurrent stroke, myocardial infarction and hemorrhagic conversion.
Although data is limited, minocycline demonstrated efficacy and seems a promising neuroprotective agent in acute stroke patients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICH patients.
KeywordsMinocycline Ischemic stroke Intracerebral hemorrhage Recovery
KM: Study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. JJC: Acquisition and interpretation of data, critical revision of the manuscript for important intellectual content. AK: Analysis and interpretation, critical revision of the manuscript for important intellectual content. DB: Acquisition and interpretation of data, critical revision of the manuscript for important intellectual content. JAS: Acquisition and interpretation of data, critical revision of the manuscript for important intellectual content. NG: Acquisition and interpretation of data, critical revision of the manuscript for important intellectual content. AVH: Analysis and interpretation, critical revision of the manuscript for important intellectual content. VP: Analysis and interpretation, critical revision of the manuscript for important intellectual content. AVA: Acquisition and interpretation of data, critical revision of the manuscript for important intellectual content. GT: Study concept and design, study supervision, critical revision of the manuscript for important intellectual content.
This study received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Compliance with ethical standards
Conflicts of interest
Dr. Malhotra reports no disclosures. Dr. Chang reports no disclosures. Dr. Khunger reports no disclosures. Dr. Blacker reports no disclosures. Dr. Switzer reports no disclosures. Dr. Goyal reports no disclosures. Dr. Hernandez reports no disclosures. Dr. Pasupuleti reports no disclosures. Dr. Alexandrov reports no disclosures. Dr. Tsivgoulis reports no disclosures.
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