Clinical effects and safety of edaravone in treatment of acute ischaemic stroke: A meta‐analysis of randomized controlled trials

Abstract

What is known and objective Edaravone is a new antioxidant and hydroxyl radical scavenger. Although there is evidence that it improves clinical outcomes of patients with acute ischaemic stroke (AIS), it is not yet widely accepted for treatment of AIS in Western countries. We further investigated the efficacy and safety of edaravone through this meta‐analysis of randomized controlled clinical trials (RCTs). Method Pubmed, Embase, Web of Science and Cochrane Library were screened up to December 2020 for original articles from SCI journals that published in English. RCTs that compared edaravone versus placebo or no intervention in adult patients and reported the efficacy or safety of edaravone were regarded as eligible. Mortality was regarded as the primary outcome and the improvement of neurological impairment was regarded as the secondary outcome. Safety evaluation was conducted according to the incidence of adverse events. Review Manager 5.3 was employed to perform the assessment of the risk of bias and data synthesis. The Cochrane risk of bias tool for randomized controlled trials was employed to assess the risk of bias. Results and discussion Seven randomized controlled trials with 2069 patients were included. For the incidence of mortality, the pooled RR for studies that evaluated edaravone after three‐month follow‐up was 0.55 (95% Cl, 0.43‐0.7, I2 = 0, P < 0.01). The pooled RR for improvement of neurological impairment at the three months follow‐up was 1.54 (95% CI, 1.27‐1.87, I2 = 0, P < 0.01) in four RCTs. On subgroup analysis of studies that were conducted in Asia, the RR was 1.56 (95% CI, 1.27‐1.90, I2 = 0%; P < 0.01); the pooled RR for studies that conducted in Europe was 1.32 (95% CI, 0.64‐2.72; P = 0.45); the pooled RR for studies that used edaravone for two weeks was 1.42 (95% CI, 1.10 to 1.83, I2 = 0%; P < 0.01); the pooled RR for studies that used edaravone for one week was 1.64 (95% CI, 1.24‐2.16, I2 = 0%; P < 0.01); the pooled RR for studies that conducted in patients with mean age equal to or over 60 years was 1.52 (95% CI, 1.24‐1.87, I2 = 0%; P < 0.01); and the pooled RR for studies that conducted in patients with mean age less than 60 was 1.80 (95% CI, 1.05‐3.08, I2 = 0%; P = 0.03). For the incidence of any treatment‐related adverse events, the pooled RR for studies that evaluated edaravone during treatment was 0.83 (95% CI, 0.51‐1.34, I2 = 0, P = 0.43). The difference of the incidence of any treatment‐related adverse events between two groups was not statistically significant. What is new and conclusion The limited studies indicate that edaravone can improve neurological impairment with a survival benefit at three‐month follow‐up, regardless of the mean age and course of treatment. It is worthy of promotion in the clinical treatment of AIS in Asian countries. More well‐designed RCTs with larger sample sizes are needed to determine the benefits of edaravone in patients from Western countries.

Adjunctive cytoprotective therapies in acute ischemic stroke: a systematic review

“…Edaravone has never reached other parts of the world, while in Japan it has been used in daily clinical stroke care since 2001. A number of clinical trials (few showed clinical benefit), meta-analyses (with positive outcomes) [156][157][158][159] and pre-clinical studies have been undertaken (all extensively reviewed elsewhere [160][161][162]), however, the majority were executed in Asian countries. Besides that, despite the described beneficial effect of Edaravone, it was also noted that these results might have been biased [163].…”

Transferrin-Enabled Blood–Brain Barrier Crossing Manganese-Based Nanozyme for Rebalancing the Reactive Oxygen Species Level in Ischemic Stroke

“…For example, edaravone (Eda), the first novel free radical scavenger approved in Japan, was used to treat IS [13]. However, it is subject to several critical problems, such as a short half-life, poor blood-brain barrier (BBB) penetration, and mediocre specificity [14,15]. Accordingly, nanoparticle-mediated ROS-scavenging strategies have been proven for the treatment of diseases induced by oxidative damage [16,17].…”

Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents

“…Most of these molecules have in common an unfused bicyclic phenyl-pyrazolone or a tricyclic phenyl-pyrazolone-phenyl central skeleton ( Figure 1 a). Structurally, these PD-L1 binders are reminiscent to the drug edaravone (1-phenyl-3-methyl-5-pyrazolone) which is used to treat amyotrophic lateral sclerosis (ALS) and acute ischaemic stroke [ 18 , 19 ].…”