Gayet-Ageron A, et al. - This study was carried out to assess the impact of treatment delay on the effectiveness of antifibrinolytics in patients with acute severe bleeding. Researchers observed that in such a patient population, death from bleeding occurred soon after onset and even a short delay in treatment attenuated the benefit of tranexamic acid administration. Immediate treatment was recommended in these patients.

Methods

• An individual patient-level data meta-analysis was performed, of randomised trials done with more than 1000 patients that examined antifibrinolytics in acute severe bleeding.
• Researchers searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PubMed, Popline, and the WHO International Clinical Trials Registry Platform to identify trials done between Jan 1, 1946, and April 7, 2017.
• Absence of death from bleeding was the primary measure of treatment benefit.
• Using logistic regression models, the effect of treatment delay on treatment effectiveness was assessed.
• Furthermore, the effect of measurement error (misclassification) was investigated in sensitivity analyses.

Results

• Data for a total of 40,138 patients was obtained from two randomised trials of tranexamic acid in acute severe bleeding (traumatic and post-partum haemorrhage).
• A total of 3558 deaths were reported, of which 1408 (40%) were ascribed to bleeding.
• The occurrence of most (884 [63%] of 1408) bleeding deaths was reported within 12 h of onset.
• Findings demonstrated that deaths from post-partum haemorrhage peaked 2–3 h after childbirth.
• Researchers found that tranexamic acid markedly increased overall survival from bleeding (odds ratio [OR] 1·20, 95% CI 1·08–1·33; p=0·001), with no heterogeneity by site of bleeding (interaction p=0·7243).
• It was also noted that treatment delay reduced the treatment benefit (p<0·0001).
• More than 70% improved survival was obtained as a result of immediate treatment (OR 1·72, 95% CI 1·42–2·10; p<0·0001).
• Thereafter, the survival benefit decreased by 10% for every 15 min of treatment delay until 3 h, after which there was no benefit.
• In addition, with tranexamic acid, no increase in vascular occlusive events was documented, with no heterogeneity by site of bleeding (p=0·5956).
• Data showed that treatment delay did not modify the effect of tranexamic acid on vascular occlusive events.