The 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

Clinical Trials Unit, London School of Hygiene and Tropical Medicine, London, UK; Emergency Department, Lausanne University Hospital, CHUV, Lausanne, Switzerland. Electronic address: fxageron@gmail.com. Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland. Clinical Trials Unit, London School of Hygiene and Tropical Medicine, London, UK. Emergency Medicine, University of Leicester, Leicester, UK.

Br J Anaesth. 2020
PICO Summary

Population

Patients with acute bleeding due to post-partum haemorrhage or trauma (2 studies, n= 28,333).

Intervention

Antifibrinolytic drugs (aprotinin, tranexamic acid, aminocaproic acid, and aminomethylbenzoic acid).

Comparison

Placebo.

Outcome

Baseline characteristics to estimate the risk of death as a result of bleeding were divided into four categories: Low (0–5%), intermediate (6–10%), high (11–20%), 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 hours after bleeding onset. There was no increased risk of vascular occlusive events with tranexamic acid and it did not vary by baseline risk categories.
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 (0-5%), intermediate (6-10%), high (11-20%), 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 (P=0.51 for interaction term). There was no increased risk of vascular occlusive events with tranexamic acid and it did not vary by baseline risk categories (P=0.25). CONCLUSIONS Tranexamic acid appears to be safe and effective regardless of baseline risk. 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.
Study details
Study Design : Systematic Review
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine