Metaanalysis of Tirilazad Mesylate in Patients with Aneurysmal Subarachnoid Hemorrhage

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Abstract
Tirilazad is a non-glucocorticoid, 21-aminosteriod that inhibits lipid peroxidation. It had neuroprotective effects in experimental ischemic stroke and reduced angiographic vasospasm after experimental subarachnoid hemorrhage (SAH). Five randomized clinical trials of tirilazad were conducted in patients with SAH. We performed a meta-analysis of these trials to assess the effect of tirilazad on unfavorable outcome, symptomatic vasospasm, and cerebral infarction after SAH. Data from 3,797 patients were analyzed and modeled using random effect and Mantel-Haenszel meta-analyses and multivariable logistic regression to determine the effect of tirilazad on clinical outcome, symptomatic vasospasm, and cerebral infarction. Clinical outcome was assessed 3 months after SAH using the Glasgow outcome scale, and symptomatic vasospasm was defined by clinical criteria with laboratory and radiological exclusion of other causes of neurological deterioration. The five trials were randomized, double-blind, and placebo-controlled. Tirilazad did not significantly decrease unfavorable clinical outcome on the GOS (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.89–1.20) or cerebral infarction (OR 1.04, 95% CI 0.89–1.22). There was a significant reduction in symptomatic vasospasm in patients treated with tirilazad (OR 0.80, 95% CI 0.69–0.93). There was no heterogeneity across the five trials. Tirilazad had no effect on clinical outcome but did decrease symptomatic vasospasm in five trials of aneurysmal SAH. The dissociation between clinical outcome and symptomatic vasospasm deserves further investigation.