Meta-Analysis of Tranexamic Acid Use in Aneurysmal Subarachnoid Hemorrhage: Efficacy, Safety, and Clinical Outcomes

Abstract

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality, with rebleeding as a major complication. Tranexamic acid (TXA), an antifibrinolytic agent, has been investigated as a potential intervention to prevent rebleeding, but its clinical utility remains controversial. Objective: To evaluate the efficacy and safety of tranexamic acid administration in patients with aneurysmal subarachnoid hemorrhage through a systematic review and meta-analysis of randomized controlled trials and observational studies. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and clinical trial registries from inception to October 2024. Studies comparing TXA with placebo or standard care in aSAH patients were included. Primary outcomes were rebleeding rates, delayed cerebral ischemia (DCI), and mortality. Secondary outcomes included functional outcomes, thrombotic complications, and length of hospital stay. Random-effects models were used to calculate pooled risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs). Results: Fourteen studies (8 RCTs and 6 observational studies) comprising 2,857 patients were included. TXA significantly reduced the risk of rebleeding (RR 0.65; 95% CI 0.49-0.85; p=0.002; I²=38%). However, no significant difference was observed in overall mortality (RR 0.91; 95% CI 0.77-1.08; p=0.29; I²=18%) or favourable functional outcomes (RR 1.06; 95% CI 0.97-1.16; p=0.21; I²=28%). TXA use was associated with an increased risk of delayed cerebral ischemia (RR 1.41; 95% CI 1.04-1.91; p=0.03; I²=62%) and hydrocephalus requiring shunting (RR 1.25; 95% CI 1.01-1.54; p=0.04; I²=15%), but not with thromboembolic events (RR 1.16; 95% CI 0.86-1.56; p=0.33; I²=21%). Conclusion: Tranexamic acid administration in aSAH effectively reduces rebleeding risk but appears to increase the risk of delayed cerebral ischemia and hydrocephalus requiring shunting. The lack of improvement in mortality or functional outcomes suggests that the benefits of rebleeding prevention may be offset by ischemic complications. Short-course, ultra-early TXA administration merits further investigation as a potential approach to optimize the risk-benefit profile in selected patients.

Keywords: Tranexamic acid, subarachnoid hemorrhage, antifibrinolytic therapy, rebleeding, delayed cerebral ischemia, meta-analysis