Safety and Efficacy of Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

 But we haven't already created protocols on this from years of research? No? Then everyone involved is incompetent.

• tranexamic acid (14 posts to March 2013)

Safety and Efficacy of Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

Junwei Ren^1†, Dongxi Qian^1†, Jiaming Wu², Lingyan Ni³, Wei Qian¹, Guozheng Zhao¹, Chuanjun Huang¹, Xing Liu¹, Yu Zou¹ and Weikang Xing^1*

• ¹Department of Neurosurgery, Suzhou Ninth People's Hospital, Suzhou, China
• ²Department of Gastroenterology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China
• ³Department of Neurology, The First People's Hospital of Taicang, Suzhou, China

Background: In recent decades, tranexamic acid (TXA) antifibrinolytic therapy before aneurysm clipping or embolization has been widely reported, but its safety and efficacy remain controversial. This meta-analysis evaluated the efficacy and safety of TXA therapy in aneurysmal subarachnoid hemorrhage (aSAH) patients, aiming to improve the evidence-based medical knowledge of treatment options for such patients.

Methods: Pubmed, Web of Science, and Cochrane Library databases were searched up to 1 March 2021 for randomized controlled trials (RCTs). We extracted safety and efficacy outcomes and performed a meta-analysis using the Review Manager software. We performed two group analyses of TXA duration and daily dose.

Results: Ten RCT studies, enrolling a total of 2,810 participants (1,410 with and 1,400 without TXA therapy), matched the selection criteria. In the TXA duration group: TXA did not reduce overall mortality during the follow-up period [RR 1.00 (95% CI 0.81–1.22)]. The overall rebleeding rate in the TXA group was 0.53 times that of the control group, which was statistically significant [RR 0.53 (95% CI 0.39–0.71)]. However, an RR of 0.43 was not statistically significant in the subgroup analysis of short-term therapy [RR 0.43 (95% CI 0.13–1.39)]. The overall incidence of hydrocephalus was significantly higher in the TXA group than in the control group [RR 1.13 (95% CI 1.02–1.24)]. However, the trend was not statistically significant in the subgroup analysis [short-term: RR 1.10 (95% CI 0.99–1.23); long-term: RR 1.22 (95% CI 0.99–1.50)]. Treatment with TXA did not cause significant delayed cerebral ischemia [RR 1.18 (95% CI 0.89–1.56)], and its subgroup analysis showed an opposite and insignificant effect [short-term: RR 0.99 (95% CI 0.79–1.25); long-term: RR 1.38 (95% CI 0.86–2.21)]. Results in the daily dose group were consistent with those in the TXA duration group.

Conclusions: Tranexamic acid does not reduce overall mortality in patients with aSAH, nor does it increase the incidence of delayed cerebral ischemia. Tranexamic acid in treating aSAH can reduce the incidence of rebleeding. However, there is no statisticalsignificance in the ultra-early short-term and low daily dose TXA therapy, which may be due to the lack of relevant studies, and more RCT experiments are needed for further study.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.asp? PROSPERO, identifier: 244079.

Introduction

Aneurysm subarachnoid hemorrhage (aSAH) accounts for 5% of all strokes and has an incidence of 7.9 per 100,000 person-years (1). The case fatality rate is ~35% due to initial hemorrhage or subsequent complications. Only 25% of the survivors have a good prognosis (2). In recent decades, tranexamic acid (TXA) antifibrinolytic therapy before aneurysm clipping or embolization has been widely reported, but its safety and efficacy remain controversial (3–6).

Rebleeding from the ruptured aneurysm increases the risk of poor outcomes and all-cause mortality (7). TXA can eliminate fibrinolysis in patients with SAH (8). At the end of the last century, many clinical studies on randomized controlled trials (RCTs) reported that TXA could significantly reduce the incidence of rebleeding in aSAH patients (5, 6, 9–11). Due to the conditions, they could not use TXA in the ultra-early stage for all patients. Moreover, simultaneously, those RCTs were mainly through the long-term (throughout the entire hospitalization) use of TXA. Although long-term antifibrinolytic therapy showed a reduction in rebleeding, the positive clinical outcome was negated by a concomitant rise in delayed cerebral ischemia (DCI) (4). However, most of all rebleeding in aSAH occur within the first 24 h (12). In 2002, Hillman J et al. found it by using TXA ultra-early (within 24 h) and for short-term (up to 72 h), a significant reduction in the rebleeding rate from 10.8 to 2.4% and an 80% reduction in the mortality rate from early rebleeding, without increasing the incidence of delayed ischemic neurological deficits (5). Unfortunately, it did not effectively improve overall mortality or clinical outcomes at 6 months (5).

With the development of diagnostic, therapeutic techniques, and materials, patients with aSAH are identified earlier and treated more successfully. Post et al.'s study, just published in 2021, had the most significant number of participants compared to any other study (13). From onset to first hospital contact for aSAH patients, the time was only 1.5 h, compared with more than 4 h in other trials (5, 6). They used the minimum daily dose of TXA (<4 g/d) for up to 24 h, greatly reducing the effects of delayed cerebral ischemia due to TXA. They noted that TXA might not significantly improve the incidence rate of rebleeding or better patient outcomes. These results were somewhat controversial with previous studies. Thus we produced this meta-analysis to evaluate the efficacy and safety of TXA therapy in aSAH patients.

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