Efficacy of High-Dose and Low-Dose Simvastatin on Vascular Oxidative Stress and Neurological Outcomes in Patient with Acute Ischemic Stroke: A Randomized, Double-Blind, Parallel, Controlled Trial

Backgrounds. Stroke is the leading cause of death and long-term disability. Oxidative stress is elevated during occurrence of acute ischemic stroke (AIS). Soluble LOX-1 (sLOX-1) and NO are used as biomarkers for vascular oxidative stress that can reflect stabilization of atherosclerotic plaque. Prev...

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Main Authors: Nattaphol Uransilp, Pannawat Chaiyawatthanananthn, Sombat Muengtaweepongsa
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Neurology Research International
Online Access:http://dx.doi.org/10.1155/2018/7268924
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author Nattaphol Uransilp
Pannawat Chaiyawatthanananthn
Sombat Muengtaweepongsa
author_facet Nattaphol Uransilp
Pannawat Chaiyawatthanananthn
Sombat Muengtaweepongsa
author_sort Nattaphol Uransilp
collection DOAJ
description Backgrounds. Stroke is the leading cause of death and long-term disability. Oxidative stress is elevated during occurrence of acute ischemic stroke (AIS). Soluble LOX-1 (sLOX-1) and NO are used as biomarkers for vascular oxidative stress that can reflect stabilization of atherosclerotic plaque. Previous study showed that simvastatin can reduce oxidative stress and LOX-1 expression. Objectives. To evaluate neurological outcomes and serum sLOX-1 and NO levels in patients with AIS treatment with low dose 10 mg/day and high dose 40 mg/day of simvastatin. Methods. 65 patients with AIS within 24 hours after onset were randomized to treatment with simvastatin 10 mg/day or 40 mg/day for 90 days. Personal data and past history of all patients were recorded at baseline. The blood chemistries were measured by standard laboratory techniques. Serum sLOX-1 and NO levels and neurological outcomes including NIHSS, mRS, and Barthel index were tested at baseline and Day 90 after simvastatin therapy. Results. Baseline characteristics were not significantly different in both groups except history of hypertension. Serum sLOX-1 and NO levels significantly reduce in both groups (sLOX-1 = 1.19±0.47 and 0.98±0.37 ng/ml; NO = 49.28±7.21 and 46.59±9.36 μmol/l) in 10 mg/day and 40 mg/day simvastatin groups, respectively. Neurological outcomes including NIHSS, mRS, and Barthel index significantly improve in both groups. However, no difference in NO level and neurological outcomes was found at 90 days after treatment as compared between low dose 10 mg/day and high dose 40 mg/day of simvastatin. Conclusion. High-dose simvastatin might be helpful to reduce serum sLOX-1. But no difference in clinical outcomes was found between high- and low-dose simvastatin. Further more intensive clinical trial is needed to confirm the appropriate dosage of simvastatin in patients with acute ischemic stroke. This trial is registered with ClinicalTrials.gov ID: NCT03402204.
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spelling doaj-art-43c586f21b774dd8b7f335c82ad5d6912025-02-03T01:03:34ZengWileyNeurology Research International2090-18522090-18602018-01-01201810.1155/2018/72689247268924Efficacy of High-Dose and Low-Dose Simvastatin on Vascular Oxidative Stress and Neurological Outcomes in Patient with Acute Ischemic Stroke: A Randomized, Double-Blind, Parallel, Controlled TrialNattaphol Uransilp0Pannawat Chaiyawatthanananthn1Sombat Muengtaweepongsa2Neurology, Faculty of Medicine, Thammasat University, Pathum Thani, ThailandDepartment of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, ThailandDepartment of Internal Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, ThailandBackgrounds. Stroke is the leading cause of death and long-term disability. Oxidative stress is elevated during occurrence of acute ischemic stroke (AIS). Soluble LOX-1 (sLOX-1) and NO are used as biomarkers for vascular oxidative stress that can reflect stabilization of atherosclerotic plaque. Previous study showed that simvastatin can reduce oxidative stress and LOX-1 expression. Objectives. To evaluate neurological outcomes and serum sLOX-1 and NO levels in patients with AIS treatment with low dose 10 mg/day and high dose 40 mg/day of simvastatin. Methods. 65 patients with AIS within 24 hours after onset were randomized to treatment with simvastatin 10 mg/day or 40 mg/day for 90 days. Personal data and past history of all patients were recorded at baseline. The blood chemistries were measured by standard laboratory techniques. Serum sLOX-1 and NO levels and neurological outcomes including NIHSS, mRS, and Barthel index were tested at baseline and Day 90 after simvastatin therapy. Results. Baseline characteristics were not significantly different in both groups except history of hypertension. Serum sLOX-1 and NO levels significantly reduce in both groups (sLOX-1 = 1.19±0.47 and 0.98±0.37 ng/ml; NO = 49.28±7.21 and 46.59±9.36 μmol/l) in 10 mg/day and 40 mg/day simvastatin groups, respectively. Neurological outcomes including NIHSS, mRS, and Barthel index significantly improve in both groups. However, no difference in NO level and neurological outcomes was found at 90 days after treatment as compared between low dose 10 mg/day and high dose 40 mg/day of simvastatin. Conclusion. High-dose simvastatin might be helpful to reduce serum sLOX-1. But no difference in clinical outcomes was found between high- and low-dose simvastatin. Further more intensive clinical trial is needed to confirm the appropriate dosage of simvastatin in patients with acute ischemic stroke. This trial is registered with ClinicalTrials.gov ID: NCT03402204.http://dx.doi.org/10.1155/2018/7268924
spellingShingle Nattaphol Uransilp
Pannawat Chaiyawatthanananthn
Sombat Muengtaweepongsa
Efficacy of High-Dose and Low-Dose Simvastatin on Vascular Oxidative Stress and Neurological Outcomes in Patient with Acute Ischemic Stroke: A Randomized, Double-Blind, Parallel, Controlled Trial
Neurology Research International
title Efficacy of High-Dose and Low-Dose Simvastatin on Vascular Oxidative Stress and Neurological Outcomes in Patient with Acute Ischemic Stroke: A Randomized, Double-Blind, Parallel, Controlled Trial
title_full Efficacy of High-Dose and Low-Dose Simvastatin on Vascular Oxidative Stress and Neurological Outcomes in Patient with Acute Ischemic Stroke: A Randomized, Double-Blind, Parallel, Controlled Trial
title_fullStr Efficacy of High-Dose and Low-Dose Simvastatin on Vascular Oxidative Stress and Neurological Outcomes in Patient with Acute Ischemic Stroke: A Randomized, Double-Blind, Parallel, Controlled Trial
title_full_unstemmed Efficacy of High-Dose and Low-Dose Simvastatin on Vascular Oxidative Stress and Neurological Outcomes in Patient with Acute Ischemic Stroke: A Randomized, Double-Blind, Parallel, Controlled Trial
title_short Efficacy of High-Dose and Low-Dose Simvastatin on Vascular Oxidative Stress and Neurological Outcomes in Patient with Acute Ischemic Stroke: A Randomized, Double-Blind, Parallel, Controlled Trial
title_sort efficacy of high dose and low dose simvastatin on vascular oxidative stress and neurological outcomes in patient with acute ischemic stroke a randomized double blind parallel controlled trial
url http://dx.doi.org/10.1155/2018/7268924
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