Tirilazad for aneurysmal subarachnoid haemorrhage

Area of Science:

• Neurology
• Clinical Trials
• Pharmacology

Background:

• Delayed cerebral ischemia (DCI) is a major cause of death and disability after aneurysmal subarachnoid hemorrhage (SAH).
• Tirilazad has demonstrated neuroprotective effects in preclinical models of cerebral ischemia.

Purpose of the Study:

• To evaluate the efficacy and safety of tirilazad in patients diagnosed with aneurysmal SAH.
• To determine if tirilazad improves clinical outcomes, such as mortality and functional status, in SAH patients.

Main Methods:

• A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing tirilazad with placebo or control.
• Searched multiple databases including Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, and EMBASE up to October 2009.
• Included five double-blind, placebo-controlled trials with 3821 patients, analyzing outcomes like death, poor outcome, DCI, and adverse events using the Peto fixed-effect method.

Main Results:

• No significant difference was observed in mortality (OR 0.89, 95% CI 0.74-1.06) or poor outcome (OR 1.04, 95% CI 0.90-1.21) between tirilazad and control groups.
• Tirilazad significantly reduced the incidence of delayed cerebral ischemia (OR 0.80, 95% CI 0.69-0.93) during the treatment period.
• Subgroup analyses did not reveal significant differences in clinical outcomes. Adverse events like leukocytosis and Q-T interval prolongation were noted in one high-dose trial.

Conclusions:

• Tirilazad, when added to nimodipine, does not provide evidence of reduced mortality or improved poor outcomes in aneurysmal SAH patients.
• The drug showed a benefit in reducing delayed cerebral ischemia, but this did not translate to improved overall clinical outcomes.