Endothelin receptor antagonists for subarachnoid hemorrhage

Area of Science:

• Neurology
• Pharmacology

Background:

• Subarachnoid hemorrhage (SAH) is a critical condition involving bleeding on the brain's surface.
• Delayed ischemic neurological deficit (DIND) and cerebral vasospasm are leading causes of mortality and disability in SAH patients.
• Endothelin, a potent vasoconstrictor, is implicated in SAH-induced DIND, making endothelin receptor antagonists (ETAs) a potential therapeutic target.

Purpose of the Study:

• To evaluate the efficacy and tolerability of endothelin receptor antagonists (ETAs) in treating subarachnoid hemorrhage (SAH).

Main Methods:

• A systematic review of randomized controlled trials (RCTs) comparing ETAs with placebo for SAH was conducted.
• Searches included major databases (Cochrane, MEDLINE, EMBASE) and additional sources to identify all relevant trials.
• Four multicenter, double-blind RCTs with 2024 participants were included, assessed for bias, and analyzed using random-effects models.

Main Results:

• ETAs significantly reduced the incidence of delayed ischemic neurological deficit (DIND) and angiographic vasospasm.
• No significant reduction was observed in unfavorable outcomes or mortality rates.
• Adverse events, including hypotension and pneumonia, were increased in the ETA group.

Conclusions:

• ETAs demonstrate potential in mitigating DIND and vasospasm following SAH.
• The overall clinical benefit remains uncertain due to observed adverse events and lack of impact on mortality.
• Further high-quality RCTs are necessary to clarify the role of ETAs in SAH management.