"The results of the study showed for the first time that neither thromboses nor embolisms occur more frequently with prophylactic TXA," Dr. Patrick Meybohm of University Hospital Wuerzburg, in Germany, told Reuters Health by email. "At the same time, it was shown that the general mortality rate and, in particular, the mortality rate due to bleeding, are significantly reduced by TXA. The results were tested and confirmed for consistency and robustness using different computational models."
As reported in JAMA Surgery, Dr. Meybohm and colleagues searched the literature from 1976 to 2020 for randomized trials comparing intravenous TXA with placebo or no treatment and analyzed 216 trials including more than 125,000 patients. They performed a meta-analysis, subgroup and sensitivity analyses, and meta-regression.
Thrombotic events (TEs) occurred in 2.1% of the TXA group and 2.0% of controls. No association was seen between TXA and risk for total TEs (risk difference, 0.001), venous thrombosis, pulmonary embolism, venous TEs, myocardial infarction or ischemia, or cerebral infarction or ischemia.
A sensitivity analysis using the risk ratio as an effect measure revealed robust effect-size estimates, and a sensitivity analysis with studies judged at low risk for selection bias showed similar results.
TXA administration was associated with a significant reduction in overall mortality and bleeding mortality but not with nonbleeding mortality. Further, an increased risk for vascular occlusive events was not found in studies including patients with a history of thromboembolism.
A comparison of studies with sample sizes of less than or equal to 99 (risk difference, 0.004), 100 to 999 (risk difference, 0.004), and greater than or equal to 1,000 (risk difference, -0.001) showed no association between TXA and incidence of total TEs.
Meta-regression of 143 intervention groups showed no association between TXA dosing and risk for venous TEs (risk difference, -0.005).
Dr. Meybohm said, "In summary, the benefits of prophylactic intravenous TXA outweigh the potential thromboembolic risk, thus forming an important component in patient blood management to prevent coagulopathy, reduce risk of bleeding and to preserve the valuable resource blood."
Dr. John Holcomb of the University of Alabama at Birmingham, coauthor of a related editorial, told Reuters Health by email, "TXA decreases bleeding if administered early but increases mortality if given late - i.e., three hours after injury. Few drugs do this, so it's important to understand the risks and benefits of this interesting drug."
"Given the large number of randomized trials, and long history of widespread use, there is little doubt that TXA is effective in the populations evaluated with high-quality data," he said. "The key message is, if you are going to use the drug in your patient population, know the right dose, give it as early as possible and monitor for the known complications."
"At this time there isn't a lab test to reliably guide TXA administration," he noted, "so use is dictated by the specific clinical scenario."
SOURCE: https://bit.ly/3x8sEnn and https://bit.ly/3goKxbJ JAMA Surgery, online April 14, 2021.
By Marilynn Larkin
Posted on
site created by:
© 2024 Medicom Medical Publishers. All rights reserved. Terms and Conditions | Privacy Policy