Tirilazad For Aneurysmal Subarachnoid Haemorrhage: A Systematic Review Of Randomized Controlled Trials

Background: Cerebrovascular spasm (CVS) is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage (SAH). Its pathogenesis has not been elucidated yet, but may be relate to free radical induced lipid peroxidation. Experimental studies have indicated that tirilazad (free radical scavenger) can prevent or reverse vasospasm. Tirilazad have been studied in several trials, but data are conflicting.Objectives: To assess the safety and efficacy of tirilazad in aneurysmal subarachnoid haemorrhage; To provide the current randomized evidence. Methods: We searched the Cochrane Controlled Trials Register (CCTR, 2004. Issue 4), Database of Abstracts of Reviews of effectiveness (4th Quarter 2004), ACP Journal Club (1991 to 12, 2005), Cochrance Databases of Systematic Review (4th Quarter 2004), Medline(1980-12,2005), CBM-disk (Chinese biological medical database, 1974 to 2004.12). In addition, we tracked down the reference lists of papers related to tirilazad. And we handsearched 10 important Chinese journals. We included all completed unconfounded truly randomized trials (RCTs) in patients with aneurysmal subarachnoid haemorrhage comparing tirilazad with control (placebo or open control) started within 4 days of the SAH onset. Two authors (WL,WB)independently assessed the methodological quality of studies and extracted data. Discussion or the third person (LM) when needed resolved the disagreement. The same two authors (WL, WB) assessed the methodological quality of each trial by recording details of the randomization method, allocation concealment, blinding, and the number of patients who were lost to follow-up and drop-out. The Revman 4.2 and the Peto method were used for data analysis.Results: We identified 12 completed RCTs, of which 6 trials (include 3838 patients) met the inclusion criteria. There was no significant deference between two groups in death from any cause at the end of the follow-up (OR 0.93; 95%CI 0.80-1.08, P=0.36).. And at the end of the follow-up, there were no significant differences between the tirilazad group and the control group in the poor outcome defined as the combined outcome of death, vegetative survival or severe disability (OR 1.01; 95%CI 0.90 — 1.15, p=0.83). Tirilazad was associated with a reduction in the incidence of symptomatic vasospasm (OR 0.81; 95%CI 0.72—0.92, P=0.001) suggesting that treatment of 17 patients would avoid one person suffering symptomatic vasospasm. The reported adverse events (local infusion-related irritation, thrombophlebitis) of tirilazad appeared to be uncommon (172/1735, 9.9%). Conclusion: There was no sufficient evidence to conclude that tirilazad is safe or effective in the treatment of aneurysmal S AH currently. These data do not support the routine use of tirilazad in the treatment of patients with aneurysmal SAH. Further high-quality randomized controlled trials should be carried out to get more reliable evidence on tirilazad for aneurysmal SAH.