Edaravone is Not Recommended as First-Line Treatment for Acute Ischemic Stroke
Based on current evidence, edaravone (MCI-186) is not recommended as a first-line treatment for acute ischemic stroke due to insufficient evidence of efficacy in improving mortality and functional outcomes.
Current Guideline Recommendations
- The American Heart Association/American Stroke Association (AHA/ASA) guidelines explicitly state that no neuroprotective agents, including edaravone, have demonstrated sufficient efficacy in improving outcomes after ischemic stroke 1.
- The 2018 AHA/ASA guidelines maintain a Class III: No Benefit recommendation (Level of Evidence A) for neuroprotective agents in acute ischemic stroke management 1.
- The guidelines specifically note that "at present, no pharmacological or non-pharmacological treatments with putative neuroprotective actions have demonstrated efficacy in improving outcomes after ischemic stroke" 1.
Evidence on Edaravone
Mechanism and Potential
- Edaravone functions as a free radical scavenger and antioxidant that theoretically could limit neuronal injury in the ischemic penumbra 1.
- In animal models, edaravone has shown promise in improving both functional and structural outcomes after focal cerebral ischemia, with reported improvements of approximately 30.3% in functional outcomes 2.
Clinical Evidence
- A small clinical trial suggested that edaravone might improve outcomes after stroke, but the AHA/ASA guidelines note that "to date, none of these agents have sufficient data to support their use" 1.
- A 2022 systematic review with meta-analysis showed that edaravone treatment was associated with improved chances of 90-day good functional outcomes (OR=1.31,95% CI 1.06-1.67) and lower mortality (OR=0.50,95% CI 0.45-0.56) 3.
- However, this meta-analysis acknowledged significant limitations: most studies were observational, conducted primarily in Asian populations (especially Japan), and demonstrated high heterogeneity across outcomes 3.
- A Cochrane review found that although edaravone appeared to increase the proportion of participants with marked neurological improvement, the risk of bias in included trials was moderate and sample sizes were small 4.
Limitations of Current Evidence
- Most studies on edaravone have been conducted in Asian populations, particularly Japan, limiting generalizability to other populations 3, 4.
- The quality of available studies is variable, with a 2016 systematic review noting an inverse relationship between study quality and effect size for functional outcomes (P<0.0017) 2.
- Effect sizes were larger in studies where randomization or blinded assessment was not reported, suggesting potential methodological issues 2.
First-Line Treatments for Acute Ischemic Stroke
- The established first-line treatments for acute ischemic stroke remain:
- Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) within the appropriate time window 1, 5.
- Endovascular thrombectomy for eligible patients with large vessel occlusions 1.
- Early initiation of antiplatelet therapy (aspirin) within 24-48 hours of stroke onset in non-thrombolyzed patients 5.
Conclusion
- While edaravone shows some promise as a neuroprotective agent, current high-quality evidence does not support its use as a first-line treatment for acute ischemic stroke 1.
- Further large, high-quality randomized controlled trials in diverse populations are needed before edaravone can be recommended as a first-line treatment 3, 4.
- Clinicians should continue to prioritize established evidence-based interventions such as timely reperfusion therapies and appropriate antiplatelet therapy 1, 5.