Research Article: Efficacy and Safety of Therapies for Acute Ischemic Stroke in China: A Network Meta-Analysis of 13289 Patients from 145 Randomized Controlled Trials

Date Published: February 13, 2014

Publisher: Public Library of Science

Author(s): Bowen Yang, Jingpu Shi, Xin Chen, Bing Ma, Hao Sun, Yu-Kang Tu.


Many of these therapies have been compared against placebos, but have not been directly compared against each other. To evaluate the efficacy and safety of several commonly used drugs for AIS directly or indirectly.

A systematic literature review was performed to identify randomized controlled trials (RCTs) published prior to April 2013 for AIS therapies. The primary outcome measures were the National Institutes of Health Stroke Scale (NIHSS) scores and the clinical effective rate. A fixed-effects meta-analysis and meta-regression are performed; lastly, performed a mixed treatment comparison was performed through the Bayesian methods.

Outcome of Efficacy of therapies for acute ischemic stroke are as followed: All of the therapies mentioned above yielded results a more effective result than placebo, Sodium ozagrel (RR 3.86, 95%CI 3.18–4.61); Sodium ozagrel + edaravone (RR 9.60, 95%CI 7.04–13.06); Edaravone (RR 4.07, 95%CI 3.30–5.01); Edaravone + Kininogenase (RR 15.33, 95%CI 10.03–23.05). The significant difference in efficacy between edaravone monotherapy and Sodium ozagrel + edaravone was evident (RR 0.43, 95%CI 0.08–0.61) and was also significant between efficacy of edaravone + Kininogenase and Sodium ozagrel (RR 4.00, 95%CI 2.47–6.24). The differences between the risk and benefit were not significant when comparing Sodium ozagrel and edaravone or edaravone + Kininogenase and Sodium ozagrel + Edaravone for AIS. Outcome of the defect of neurological function: Placebo served a significant difference in treating the defects of neurological function compared with Sodium ozagrel (WMD = −3.11, 95%CI −4.43 to −1.79), Sodium ozagrel + edaravone (WMD = −6.25, 95%CI −7.96 to −4.54) and Edaravone + Kininogenase (WMD =  −3.47, 95%CI −5.73 to −1.21).

It provides that the efficacy of edaravone monotherapy in treatment was not more effective than Sodium ozagrel + edaravone.The efficacy of edaravone + Kininogenase monotherapy in treatment was more effective than Sodium ozagrel. Edaravone + Kininogenase and Sodium ozagrel + Edaravone appeared the most effective treatments. And Sodium ozagrel, Sodium ozagrel + edaravone, Edaravone + Kininogenase can improve the nerve dysfunction.

Partial Text

Stroke is the second most common cause of death and the major cause of disability worldwide, preceded only by heart attack. The burden of stroke will increase greatly in the next 20 years, especially in developing countries, due to the aging of population [1]. About 80% of all acute strokes are caused by cerebral infarction, usually resulting from thrombotic or embolic occlusion of a cerebral artery [2]. In addition, China must face the greatest number of cases of stroke due to its 1.34 billion population accounted for as of 2011 [3]. The epidemiological data shows that from 1984 to 2004 the incidence of ischemic stroke as the most common subtype, representing about 80% of all strokes, and has increased by 8.7% per year even though the incidence of hemorrhagic stroke decreased by 1.7% every year in China [3]. Guideline from the American Heart Association/American Stroke Association for the patients’ early management of acute ischemic stroke remains multifaceted, and includes several aspects of care that have not been tested in clinical trials [4]. Although data from some experimental and human studies have suggested that edaravone and Sodium ozagrel, the neuroprotective agent, may be beneficial for people with acute ischemic stroke, It has been widely used in China to treat stroke [5], [6], the comparisons of these drugs or combined treatments were unclear.

We conducted a network meta-analysis using a Bayesian analytic framework applied to data abstracted from the RCTs in order to simultaneously compare therapies that have not previously been directly compared. These results summaries experience of the treatment of acute cerebral stroke in short-term clinical trials, incorporating both direct and indirect comparisons of agents, including those that have never been compared directly (i.e. edaravone versus Sodium ozagrel combined with edaravone). The network meta-analysis technique overcomes the significant heterogeneity in traditional meta-analysis for several drug classes versus all other treatment of acute cerebral stroke in short-term clinical trials. Due to the reason that it can attribute risk across all classes of initial treatment of acute cerebral stroke in short-term clinical trials, rather than being restricted to comparisons of one class versus all other classes. The findings of this network meta-analysis are robust, in terms of both the low estimate of incoherence within the model itself, and in sensitivity analyses.