Background: The CRASH-2 trial demonstrated that tranexamic acid (TXA) safely reduces mortality in injured adults with significant traumatic hemorrhage. TXA has since been widely used in injured adults worldwide. Our objective was to evaluate mortality and complication rates in adults with trauma in studies reported after the CRASH-2 trial.
Methods: We systematically searched PubMed, Embase, MicroMedex, and ClinicalTrials.gov for studies that included injured adults who received TXA and reported mortality and/or adverse events. We excluded case reports and review articles. Each study was reviewed by two reviewers who independently assessed study eligibility, abstracted data, and assessed risk of bias. Prior to pooling of data, group consensus was reached to resolve discrepancies in data abstraction and quality assessment, and to exclude studies from the meta-analysis based on clinical heterogeneity. We conducted meta-analyses using random effects models to estimate the incidence of mortality at 28 or 30 days and in-hospital thrombotic events. I-square statistic was calculated to estimate degree of heterogeneity.
Results: Nineteen and thirteen studies were included in the systematic review and meta-analysis respectively. There were 13 retrospective studies, 5 prospective observational studies, and 1 randomized controlled trial. Reasons for exclusion from meta-analyses included: survival criterion (3 studies), selective injury criterion (2 studies), and hyperfibrinolytic patients only (1 study). The pooled incidence of mortality at 28 or 30 days (5 studies, 1538 patients) was 10.1% (95%CI 7.8-12.4%) (versus 14.5% [95%CI 13.9-15.2%] in the CRASH-2 trial), and the pooled incidence of in-hospital thrombotic events (9 studies, 1656 patients) was 5.9% (95%CI 3.3-8.5%) (versus 2.0% [95%CI 1.8-2.3%] in the CRASH-2 trial). Considerable heterogeneity was observed in in-hospital thrombotic events among included studies.
Conclusion: Compared to the CRASH-2 trial, adult trauma patients receiving TXA identified in our meta-analysis had a lower incidence of mortality at 28 or 30 days, but a higher incidence of in-hospital thrombotic events. Our results neither support nor refute the findings of the CRASH-2 trial, but suggest that incidence rates in adults with trauma in settings outside of the CRASH-2 trial may be different than those observed in the CRASH-2 trial.