Positive Safety Evaluation for Tranexamic Acid
A large meta-analysis upheld the safety of tranexamic acid (TXA), even at higher doses.
TXA is an antifibrinolytic agent with a short half-life that is used for bleeding prevention and treatment, as in causes of trauma with open wounds. Current TXA is applied with caution due to perceived increased risk of seizures, MI, and other thrombotic complications.
The meta-analysis looked at 216 randomised trials involving 125 550 participants. The investigators found that the incidence of thromboembolic events, which included venous thrombosis, pulmonary embolism, venous thromboembolism, myocardial infarction (MI) or ischaemia, and cerebral infarction or ischaemia, was 2.1% of people receiving IV TXA and a similar 2.0% of peers getting placebo or another control, which was a non-significant difference.
TXA’s safety was inconclusive in those with neurological conditions, who showed increased heterogeneity and asymmetry in funnel plots, according to Patrick Meybohm, MD, of University Hospital Wuerzburg in Germany, and colleagues.
The review confirmed that TXA was linked to a significant reduction in overall mortality and bleeding mortality, but not nonbleeding mortality.
“The results of this study suggest that use of intravenous TXA may have utility in all medical fields, with some uncertainty for patients with neurological conditions,” the investigators concluded.
“Notably, we did not detect any dose-dependent association of TEs [thromboembolic events],” they stated. The included studies had participants with IV TXA administration at doses ranging 0.5-5g or 10-100mg/kg.
“There is little doubt that when used appropriately in the various patient populations evaluated with randomized clinical trials, TXA is effective. However, reasonable questions about thrombotic complications remain,” wrote John Holcomb, MD, of University of Alabama at Birmingham, and colleagues, in an invited commentary.
“Further research must focus on how to identify, as early as possible, the patients most likely to benefit from administration of TXA,” they urged.
One limitation mentioned by the investigators was the inclusion trials that evaluated thromboembolic events without ultrasound, so asymptomatic cases may have been excluded. Furthermore, many studies did not provide much information on thrombosis prophylaxis.
For Holcomb’s group, study’s main caveat was that it included “a notably heterogeneous population”, including a range of demographics and clinical conditions. Since the pooled studies were not “clinically homogeneous”, they violated “one of the cardinal tenets of systematic reviews and meta-analyses.”
Source: MedPage Today
Journal information (primary article): Taeuber I, et al “Association of intravenous tranexamic acid with thromboembolic events and mortality: a systematic review, meta-analysis, and meta-regression” JAMA Surg 2021; DOI: 10.1001/jamasurg.2021.0884.
Journal information (commentary): Holcomb JB, et al “Tranexamic acid and safety in the right patient” JAMA Surg 2021; DOI: 10.1001/jamasurg.2021.0929.
