Safety and Efficacy of Neuroprotective Agents as Adjunctive Therapies for Reperfusion in the Treatment of Acute Ischemic Stroke: A Systematic Review and Meta-analysis of Randomized Controlled Trials

There is still no clear evidence of the efficacy of the application of neuroprotective agents (NPAs) for acute ischemic stroke (AIS) patients receiving reperfusion therapies. This meta-analysis aimed to determine the effects of NPAs versus placebo on functional and safety outcomes as an adjunctive treatment to intravenous thrombolysis (IVT) or endovascular therapy (EVT) in AIS patients. The primary outcome was neurological functional independence, as evaluated by the proportion of patients whose modified Rankin Scale scores were 0 to 2 at 90 days after treatment. Thirteen randomized controlled trials with a total of 3736 patients were included. The application of NPAs was associated with greater odds of functional independence (odds ratio [OR]: 1.28; 95% CI: 1.12 to 1.46; P < 0.001; I2 = 0.0%) within 90 days. However, subgroup analysis of reperfusion therapy type (IVT, EVT, or both) revealed that only the EVT subgroup showed a significant association between NPAs or placebo and functional independence at 90 days (EVT group, OR: 1.43; 95% CI: 1.05 to 1.94; P = 0.022; I2 = 0.0%; IVT group, OR: 1.51; 95% CI: 0.93 to 2.46; P = 0.099; I2 = 39.8%; IVT plus EVT group, OR: 1.17; 95% CI: 0.94 to 1.45; P = 0.157; I2 = 16.0%). This meta-analysis revealed that NPAs could increase the possibility of AIS patients undergoing reperfusion therapies achieving functional independence within 90 days of onset; however, with the limited number of studies on each drug, further evidence is still needed to demonstrate the efficacy of each individual agent as an adjunctive therapy for different means of reperfusion.