Safety of edaravone in acute ischemic stroke: A systematic review and meta-analysis

Background & Objective: Stroke is a major cause of death and disability, however many patients do not benefit from time-limited reperfusion therapies. Edaravone is a neuroprotective agent that has been shown to improve neurologic impairment after ischemic stroke. This paper aims to review and synthesize evidence on the safety of edaravone in acute ischemic stroke. Methods: This is a systematic review and meta-analysis of randomized controlled trials and observational studies on the use of edaravone with standard stroke treatment, versus standard stroke treatment alone, among patients with acute ischemic stroke. Mortality was regarded as the primary outcome. Secondary outcomes of interest were other neurologic safety outcomes (intracerebral hemorrhage, hemorrhagic transformation) and systemic safety outcomes (renal and hepatic impairment, other adverse drug reactions). Results: 15 studies were included. The total number of study participants was 15,654, with 81.5% given edaravone and 18.4% given control. Overall, edaravone treatment was associated with a significantly reduced risk of mortality compared to control (RR 0.63, p<0.00001, 0.95% CI 0.52-0.75). Among ischemic stroke patients given reperfusion therapy, edaravone treatment was associated with lower risk of intracerebral hemorrhage (RR 0.77, 95% CI 0.32-1.84), symptomatic intracerebral hemorrhage (RR 0.55, 95% CI 0.16-1.84) and hemorrhagic transformation (RR 0.68, 95% CI 0.32-1.41), however results were not statistically significant. Conclusions: Current evidence suggests that the use of edaravone in addition to standard treatment among patients with acute ischemic stroke is associated with lower risk of mortality. Larger high- quality trials outside Asia with longer length of follow-up are recommended for further investigation.