Endothelin receptor antagonists for subarachnoid hemorrhage

Endothelin receptor antagonists appear to reduce delayed ischemic neurological deficit and angiographic vasospasm in subarachnoid hemorrhage but at the cost of adverse events and the impact on clinical outcome appears to be unclear.

Summary

A Cochrane review included 4 studies with a total of 2024 subjects with subarachnoidal haemorrhage. The trials compared endothelin receptor antagonists (ETA, clazosentan in 3 trials and investigational product TAK-044 in one trial) with placebo over 10 to 14 days. ETAs reduced the incidence of delayed ischemic neurological deficit (DIND) (RR 0.80; 95% CI 0.67 to 0.95; 3 studies, n=1976) and angiographic vasospasm (RR 0.62; 95% CI 0.52 to 0.72; 3 studies, n=1588). However, it did not reduce the incidence of unfavorable outcomes (RR 0.87; 95% CI 0.74 to 1.02; 3 studies, n=1976) or mortality (RR 1.05; 95% CI 0.77 to 1.45; 4 studies, n=2024). ETAs increased the incidence of hypotension (RR 2.53; 95% CI 1.77 to 3.62; 4 studies, n=2024) and pneumonia (RR 1.56; 95% CI 1.23 to 1.97; 3 studies, n=1976).

Comment: The quality of the evidence is downgraded by indirectness (differences in outcomes).

Clinical comments

Date of latest search:

Ədəbiyyat

1. Guo J, Shi Z, Yang K et al. Endothelin receptor antagonists for subarachnoid hemorrhage. Cochrane Database Syst Rev 2012;9:CD008354.