Effect of tranexamic acid by baseline risk of death in acute bleeding patients: a meta-analysis of individual patient-level data from 28 333 patients

Abstract

Background: Early administration of the antifibrinolytic drug tranexamic acid reduces death from bleeding in trauma and postpartum haemorrhage. We examined how the effectiveness and safety of antifibrinolytic drugs varies by the baseline risk of death as a result of bleeding. Methods: We performed an individual patient-level data meta-analysis of randomised trials including more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials performed between January 1, 1946 and July 5, 2018 (PROSPERO, number 42016052155). Results: Two randomised trials were selected where 28 333 patients received tranexamic acid treatment within 3 h after the onset of acute bleeding. Baseline characteristics to estimate the risk of death as a result of bleeding were divided into four categories: Low (0e5%), intermediate (6e10%), high (11e20%), and very high (>20%). Most patients had a low baseline risk of death as a result of bleeding (23 008 [81%]). Deaths as a result of bleeding occurred in all baseline risk categories with 240 (1%), 202 (8%), 232 (14%), and 357 (30%) deaths in the low-, intermediate-, high-, and very high-risk categories, respectively. The effectiveness of tranexamic acid did not vary by baseline risk when given within 3 h after bleeding onset (P¼0.51 for interaction term). There was no increased risk of vascular occlusive events with tranexamic acid and it did not vary by baseline risk categories (P¼0.25). Conclusions: Tranexamic acid appears to be safe and effective regardless of baseline risk of death. Because many deaths are in patients at low and intermediate risk, tranexamic acid use should not be restricted to the most severely injured or bleeding patients.

Validation of the BATT score for prehospital risk stratification of traumatic haemorrhagic death: usefulness for tranexamic acid treatment criteria

“…We estimated the impact of TXA treatment for each treatment criteria. Since randomized trials of TXA in trauma patients report no increase in deaths from adverse events, the net impact of TXA was given by the number of deaths due to bleeding avoided by the treatment [ 6 , 17 ]. To estimate the number of deaths avoided by TXA, we predicted the baseline risk of death due to bleeding using our previously published prognostic model [ 5 ].…”

Validation of the BATT score for prehospital risk stratification of traumatic haemorrhagic death: Usefulness for tranexamic acid treatment criteria.

“…Since randomized trials of TXA in trauma patients report no increase in deaths from adverse events, the net impact of TXA was given by the number of deaths due to bleeding avoided by the treatment. [14,15] To estimate the number of deaths avoided by TXA, we predicted the baseline risk of death due to bleeding using our previously published prognostic model. [5] To estimate post-treatment probabilities, we applied the treatment effect to these baseline risks taking into account time to treatment.…”

Validation of the BATT score for prehospital risk stratification of traumatic haemorrhagic death: Usefulness for tranexamic acid treatment criteria.

“…Since randomized trials of TXA in trauma patients report no increase in deaths from adverse events, the net impact of TXA was given by the number of deaths due to bleeding avoided by the treatment. [6,14] To estimate the number of deaths avoided by TXA, we predicted the baseline risk of death due to bleeding using our previously published prognostic model. [5] To estimate post-treatment probabilities, we applied the treatment effect to these baseline risks taking into account time to treatment.…”

“…We previously developed a prognostic model to predict death from bleeding and showed that the relative reduction in mortality with TXA does not vary with baseline risk. [5,6] Because many deaths are in patients at low and intermediate risk, TXA use should not be restricted to the most severely injured. [6] In this study, we derive a simple score that paramedics can use at the scene to help decide who to treat with TXA.…”

“…[5,6] Because many deaths are in patients at low and intermediate risk, TXA use should not be restricted to the most severely injured. [6] In this study, we derive a simple score that paramedics can use at the scene to help decide who to treat with TXA. We conduct an external validation of the score and explore different TXA treatment thresholds.…”