Safety and Efficacy of Tranexamic Acid as an Antifibrinolytic Agent for the Management of Aneurysmal Subarachnoid Hemorrhage: Meta-analysis of Rebleeding and Neurological Recovery

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) is a significant cause of morbidity and mortality worldwide. A primary reason that aSAH is clinically challenging is that it poses a significant risk for rebleeding even when the source of the sentinel bleed, such as a ruptured aneurysm, is successfully repaired and the patient adequately stabilized. Equally as important in treating aSAH is the prevention of aneurysm re-rupture. For this reason, administering antifibrinolytic agents that can effectively stabilize clot formation following the sentinel bleed could prove efficacious in treating aSAH. One such agent is tranexamic acid (TXA), an antifibrinolytic agent that has been described as ten times more effective than aminocaproic acid. However, there remain concerns related to TXA’s tendency to cause thrombotic complications—including pulmonary emboli (PE) and other venous thromboembolic events (VTEs)—that can lead to postoperative mortality. In the present study, we systematically review the neurosurgical literature to outline the extant evidentiary base informing the use of TXA to prevent rebleeding in patients with aSAH secondary to aneurysmal rupture.

Methods: We queried three databases to identify all studies investigating the therapeutic role of antifibrinolytic agents for reducing rebleeding, morbidity, and mortality in aSAH. Articles returned by the query were screened by title and abstract and subsequently by full text according to two authors' predetermined inclusion and exclusion criteria. Data were pooled, and a meta-analysis of the following outcomes was performed: rates of rebleeding, neurologic outcomes, TXA-associated complications, vasospasm, and VTEs. For all analyses, p-values < 0.05 were deemed statistically significant.

Results: Our search returned 16 studies (12 Level I Evidence RCTs, 4 Level II nonrandomized or non-blinded, controlled prospective trials) featuring 3,396 patients treated for aSAH. Consistent with previous reports within the literature, TXA successfully reduced rates of rebleeding in aSAH patients who were administered TXA status-post sentinel bleed (RR 0.56, 95% CI [0.42, 0.75], I ² = 52%, p < 0.001). However, it did not confer benefits with respect to vasospasm prevention or neurological outcomes.

Conclusion: Using the highest-level data available within the literature (Levels I–II), we determined that – although TXA does not appear to influence the rate of post-aSAH vasospasm – it does reduce rates of rebleeding and, therefore, can be administered to help optimize neurologic outcomes in patients who do not have underlying risk factors for adverse events secondary to TXA.

Publication History

Article published online:
07 February 2025