Ozagrel for acute ischemic stroke: a meta-analysis of data from randomized controlled trials

Background: In patients with acute ischemic stroke (AIS), platelets are activated in the acute phase, releasing neurotoxic, and thrombogenic eicosanoids, which may reduce the brain blood flow and cause brain damage. Sodium ozagrel (ozagrel), a thromboxane A2 synthase inhibitor, is one of the most studied drugs which may reduce the risk of neurological impairment and reduce the volume of brain damage. We systematically reviewed all published randomized controlled trials (RCTs) comparing ozagrel with control among patients with AIS. Methods: We searched seven databases, using the Cochrane Stroke Group search strategy and the terms of ozagrel and stroke. Two independent investigators evaluated trial quality using the Cochrane Collaboration's risk of bias tool and extracted the data from each study. Pooled analyses for the outcomes of combined death or disability and improvement of neurological impairment were calculated. Results: The effect of ozagrel on the reduction of death for AIS at the end of follow-up was relative risk (RR)=50.67 (95% CI: 0.11 to 4.04, P=0.67). The effect evaluated by Modified Edinburgh-Scandinavian Stroke Scale (MESSS) at the end of treatment was mean difference (MD)=-4.17 (95% CI, -4.95 to -3.40; P<0.00001). The most severe adverse events of ozagrel were digestive hemorrhage and hemorrhagic stroke; however, there was no significant difference between the two groups. The subgroup analysis of different dose showed that 80 and 160 mg ozagrel per day might both increase the improvement of the neurological impairment. Discussion: During scheduled treatment, ozagrel is effective for the improvement of neurological impairment for AIS patients. However, the evidence of ozagrel to reduce the long-term death or disability is limited and quality of these trials is insufficent hence, large-sample and high quality RCTs are warrented to confirm the efficacy of ozagrel for acute ischemic stroke.