Effect of age on the efficacy of tranexamic acid: An analysis of heterogeneity of treatment effect within the CRASH-2 dataset.

Abstract

Trauma is a major cause of morbidity and mortality in older adults and will become more common as the population ages. Tranexamic acid (TXA) is a lysine analogue frequently used in the setting of significant trauma with hemorrhage. The aim of this study is to investigate the heterogeneity of treatment effect of TXA as it relates to patient age during trauma care. We included patients from the CRASH-2 trial who were randomized within 3h of injury. Patients were stratified into age groups <26years, 26 to 35years, 36 to 45years, 46 to 55years, and>55years. Multiple logistic regression models were utilized to evaluate adjusted odds ratios (OR) with 95% confidence intervals (CI) for mortality. Heterogeneity of treatment effect was evaluated using Akaike and Bayesian information criteria to determine the optimum logistic regression model after which a Wald Chi-square test was utilized to evaluate statistical significance. On univariate analysis, TXA administration decreased mortality within the <26years cohort (decrease of 2.1%, 95% CI 0.2 to 4.0), 46 to 55years cohort (decrease 6.7%, 95% CI 2.7 to 10.7), and>55years cohort (decrease of 5.3%, 95% CI 0.4 to 10.3). On adjusted analysis, when compared to the 36 to 45years cohort, the <26year cohort experienced a decreased mortality (OR 0.72, 95% CI 0.62 to 0.85) whereas the >55year cohort experienced increased mortality (OR 1.8, 95% CI 1.5 to 2.2). Assessment for heterogeneity of treatment effect of TXA administration between groups approached but did not reach statistical significance (p=0.11). Mortality related to trauma increases with age, however, there does not appear to be heterogeneity of treatment effect for TXA administration among different age groups.