Efficacy and safety of tranexamic acid administration for subarachnoid hemorrhage: A systematic review and meta-analysis

Eriya Imai¹Hiroshi Ito²Hiromu Okano^3*Akihiko Inoue⁴Takero Terayama⁵HIROSHI OKAMOTO³Toru Hifumi³Yoshihisa Fujimoto⁶Gaku Fujiwara⁷Yasuhiro Kuroda⁸

• ¹Mitsui Memorial Hospital, Tokyo, Japan
• ²Osaka University, Suita, Japan
• ³St. Luke's International Hospital, Tokyo, Japan
• ⁴Hyogo Emergency Medical Center, Hyogo, Japan
• ⁵Self-Defense Forces Central Hospital, Tokyo, Japan
• ⁶St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
• ⁷Kyoto University, Kyoto, Kyōto, Japan
• ⁸Kagawa University, Takamatsu, Kagawa, Japan

Aneurysmal subarachnoid hemorrhage (SAH) carries a high risk of early rebleeding and worsens prognosis. Tranexamic acid (TXA), an antifibrinolytic agent, can prevent rebleeding; however, its effects on mortality and neurological outcomes remain controversial. This review evaluated the efficacy and safety of TXA with SAH. MEDLINE, CENTRAL, EMBASE, ICTRP, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) to assess TXA use in SAH. Studies comparing TXA with controls with SAH were included. The primary outcome was the mortality; secondary outcomes included neurological outcomes, rebleeding, thromboembolism, delayed cerebral ischemia (DCI), hydrocephalus, and adverse events. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Fifteen RCTs (3,109 patients) and nine NRSIs (1,506 patients) were included. RCTs demonstrated that TXA likely does not reduce mortality (risk ratio [RR], 1.00; 95% confidence interval [CI], 0.82–1.22; moderate certainty) and neurological outcome, and may not increase thromboembolism and DCI. However, TXA probably reduces rebleeding but probably increases hydrocephalus. The NRSIs results were similar. Although routine use is not supported, TXA may be considered for high-risk patients when early aneurysm treatment is unavailable. Registeration: Registered in the Open Science Framework (https://osf.io/yp78b/).