Konark Malhotra1, Jason J Chang2, Arjun Khunger3, David Blacker4, Jeffrey A Switzer5, Nitin Goyal6, Adrian V Hernandez7,8, Vinay Pasupuleti9, Andrei V Alexandrov6, Georgios Tsivgoulis6,10. 1. Department of Neurology, Charleston Area Medical Center, West Virginia University-Charleston Division, Charleston, WV, 25301, USA. konark.malhotra@yahoo.com. 2. Department of Critical Care Medicine, MedStar Washington Hospital Center, Washington, DC, USA. 3. Department of Hematology and Oncology, Cleveland Clinic Foundation, Cleveland, OH, USA. 4. Department of Neurology and Clinical Neurophysiology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. 5. Department of Neurology, Medical College of Georgia at Augusta University, Georgia, USA. 6. Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA. 7. University of Connecticut/Hartford Hospital Evidence-based Practice Center, Hartford, CT, USA. 8. School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru. 9. ProEd Communications Inc., Cleveland, OH, USA. 10. Second Department of Neurology, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens, Greece.
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 Of these, additional unpublished data was obtained on contacting corresponding authors of 5 RCTs.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.
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 strokepatients 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 strokepatients, especially in AIS subgroup. Further RCTs are needed to evaluate the efficacy and safety of minocycline among ICHpatients.
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