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Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials

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Abstract

Background

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.

Methods

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.

Results

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 Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs.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.

Conclusions

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.

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Funding

This study received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Neurology, Charleston Area Medical Center, West Virginia University-Charleston Division, Charleston, WV, 25301, USA

    Konark Malhotra

  2. Department of Critical Care Medicine, MedStar Washington Hospital Center, Washington, DC, USA

    Jason J. Chang

  3. Department of Hematology and Oncology, Cleveland Clinic Foundation, Cleveland, OH, USA

    Arjun Khunger

  4. Department of Neurology and Clinical Neurophysiology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia

    David Blacker

  5. Department of Neurology, Medical College of Georgia at Augusta University, Georgia, USA

    Jeffrey A. Switzer

  6. Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA

    Nitin Goyal, Andrei V. Alexandrov & Georgios Tsivgoulis

  7. University of Connecticut/Hartford Hospital Evidence-based Practice Center, Hartford, CT, USA

    Adrian V. Hernandez

  8. School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru

    Adrian V. Hernandez

  9. ProEd Communications Inc., Cleveland, OH, USA

    Vinay Pasupuleti

  10. Second Department of Neurology, National and Kapodistrian University of Athens, “Attikon” University Hospital, Athens, Greece

    Georgios Tsivgoulis

Authors
  1. Konark Malhotra
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  2. Jason J. Chang
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Contributions

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.

Corresponding author

Correspondence to Konark Malhotra.

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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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Malhotra, K., Chang, J.J., Khunger, A. et al. Minocycline for acute stroke treatment: a systematic review and meta-analysis of randomized clinical trials. J Neurol 265, 1871–1879 (2018). https://doi.org/10.1007/s00415-018-8935-3

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  • DOI: https://doi.org/10.1007/s00415-018-8935-3

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