The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial
Annals of emergency medicine. 2021
STUDY OBJECTIVE Epistaxis is a common emergency department (ED) presentation and, if simple first aid measures fail, can lead to a need for anterior nasal packing. Tranexamic acid is an agent that contributes to blood clot stability. The aim of this study is to investigate the effectiveness of topical intranasal tranexamic acid in adult patients presenting to the ED with persistent epistaxis, and whether it reduces the need for anterior nasal packing. METHODS From May 5, 2017, to March 31, 2019, a double-blind, placebo-controlled, multicenter, 1:1, randomized controlled trial was conducted across 26 EDs in the United Kingdom. Participants with spontaneous epistaxis, persisting after simple first aid and the application of a topical vasoconstrictor, were randomly allocated to receive topical tranexamic acid or placebo. The primary outcome was the need for anterior nasal packing of any kind during the index ED attendance. Secondary outcome measures included hospital admission, need for blood transfusion, recurrent epistaxis, and any thrombotic events requiring any hospital reattendance within 1 week. RESULTS The study sample consisted of 496 participants with spontaneous epistaxis, persisting after simple first aid and application of a topical vasoconstrictor. In total, 211 participants (42.5%) received anterior nasal packing during the index ED attendance, including 111 of 254 (43.7%) in the tranexamic acid group versus 100 of 242 (41.3%) in the placebo group. The difference was not statistically significant (odds ratio 1.107; 95% confidence interval 0.769 to 1.594; P=.59). Furthermore, there were no statistically significant differences between tranexamic acid and placebo for any of the secondary outcome measures. CONCLUSION In patients presenting to an ED with atraumatic epistaxis that is uncontrolled with simple first aid measures, topical tranexamic acid applied in the bleeding nostril on a cotton wool dental roll is no more effective than placebo at controlling bleeding and reducing the need for anterior nasal packing.
Efficacy of topical tranexamic acid in epistaxis: A systematic review and meta-analysis
The American journal of emergency medicine. 2021;51:169-175
INTRODUCTION Epistaxis is a very common presentation in the emergency department (ED), accounting for approximately 1 in 200 ED visits in the United States. Currently, standard practice includes the initial use of topical anesthetics and vasoconstrictors, followed by more invasive treatments such as nasal packing, cauterization or surgical ligation for refractory cases. Over the years several studies have investigated the potential use of topical Tranexamic Acid (TXA) in the management of epistaxis. We have conducted a meta-analysis to assess the efficacy of topical TXA versus other standard practices or placebo in the management of epistaxis. METHODS PubMed and Scopus databases were searched from inception to April 2021. We included randomized controlled trials and observational studies investigating the efficacy of TXA in bleeding cessation in epistaxis in adults. The primary outcome measured was the prevalence of bleeding cessation after treatment at first assessment. Other outcomes were bleeding reoccurrence between 24 and 72 h and at 7-8 days. A random-effects model was used to estimate odds ratio (OR) for outcomes. RESULTS A total of eight studies were included in the analysis, including seven randomized trials and one retrospective study. We included a total of 1299 patients, 596 (46%) received TXA while 703 (54%) received control treatment (placebo, lidocaine plus vasoconstrictors or local anesthetics). Patients who were treated with TXA were 3.5 times (OR 3.5, 95% CI 1.3-9.7) more likely to achieve bleeding cessation at the first assessment. Patients treated with TXA had 63% (OR 0.37, 95% CI 0.20-0.66) less likelihood of returning due to rebleeding at 24-72 h. CONCLUSION Topical TXA is associated with better bleeding cessation rates after treatment compared to the standard practices.
Risk of venous and arterial thrombosis in non-surgical patients receiving systemic tranexamic acid: A systematic review and meta-analysis
Thrombosis research. 2019;179:81-86
BACKGROUND Antifibrinolytic agents such as tranexamic acid (TXA) are commonly used as adjunctive therapies to prevent and treat excessive bleeding. In non-surgical settings, TXA is known to reduce bleeding related mortality. However, impact of TXA use on thrombosis is uncertain. METHODS We systematically searched the MEDLINE, EMBASE, and CENTRAL databases from January 1985 to August 2018. Studies with the following characteristics were included: (i) RCT design; (ii) compared systemic (oral or intravenous) TXA for prevention or treatment of bleeding for non-surgical indications and placebo or no TXA, and (iii) reported thrombotic events or mortality. A Mantel-Haenzel, random-effects model was used to calculate risk ratios, and risk of bias was assessed using the Cochrane risk of bias tool. RESULTS Our search identified 22 studies representing 49,538 patients. Those receiving TXA had a significantly lower risk of death from any cause (RR=0.92; 95% CI=0.87-0.98; I(2)=0%). There was no significant increase in the risk of stroke (RR=1.10; 95% CI=0.68-1.78; I(2)=31%), myocardial infarction (RR=0.88; 95% CI=0.43-1.84; I(2)=46%), pulmonary embolism (RR=0.97; 95% CI=0.75-1.26; I(2)=0%), or deep vein thrombosis (RR=0.99; 95% CI=0.70-1.41; I(2)=0%) from use of TXA. The results were similar when restricted to studies at low risk of bias. CONCLUSIONS In our systematic review and meta-analysis, the use of tranexamic acid reduced all-cause mortality without increased risk of venous or arterial thrombotic complications.
Tranexamic Acid in Cerebral Hemorrhage: A Meta-Analysis and Systematic Review
CNS drugs. 2019
BACKGROUND Tranexamic acid functions as an antifibrinolytic medication and is widely used to treat or prevent excessive blood loss in menorrhagia and during the perioperative period. The efficacy of tranexamic acid in reducing mortaligy and disability, and the occurrence of complications during treatment of cerebral hemorrhage remains controversial. OBJECTIVE The objective of this systematic literature review and meta-analysis was to evaluate the efficacy and safety of tranexamic acid in patients with cerebral hemorrhage, aiming to improve the evidence-based medical knowledge of treatment options for such patients. METHODS A systematic literature search was performed in English through 31 August 2018, with two reviewers independently extracting data and assessing risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias. RESULTS In total, 14 randomized controlled trials with 4703 participants were included in the meta-analysis. Tranexamic acid did not improve mortality by day 90 (odds ratio (OR) 0.99; 95% confidence interval (CI) 0.84-1.18; p = 0.95) or day 180 (OR 1.01; 95% CI 0.51-2.01; p = 0.98) or overall death endpoints of different follow-up times (OR 0.82; 95% CI 0.62-1.08; p = 0.15), which was supported by sensitivity analysis of studies published during or after 2000 (OR 0.92; 95% CI 0.77-1.09; p = 0.33). A lower incidence of hematoma expansion (OR 0.54; 95% CI 0.37-0.80; p = 0.002) and less change in volume from baseline (mean difference (MD) - 1.98; 95% CI - 3.00 to - 0.97; p = 0.0001) were observed, but no change was seen in poor functional outcomes (OR 0.95; 95% CI 0.79-1.14; p = 0.55) in the tranexamic acid group. The risk of hydrocephalus (OR 1.21; 95% CI 0.90-1.62; p = 0.21), ischemic stroke (OR 1.43; 95% CI 0.87-2.34; p = 0.16), deep vein thrombosis (OR 1.25; 95% CI 0.75-2.08; p = 0.40), and pulmonary embolism (OR 0.97; 95% CI 0.59-1.58; p = 0.89) was similar, whereas the risk of combined ischemic events increased in the tranexamic acid group (OR 1.47; 95% CI 1.07-2.01; p = 0.02). CONCLUSIONS Treatment with tranexamic acid could reduce rebleeding and hematoma expansion in cerebral hemorrhage without an increase in single ischemic adverse events, but it could increase the risk of combined ischemic events; however, the lack of improvement in mortality and the poor functional outcomes limit the value of clinical application. These findings indicate that the most pertinent issue is the risk-to-benefit ratio with tranexamic acid treatment in cerebral hemorrhage.
A multicenter double blind clinical trial on 3.4.5-trimethoxybenzoiyl-epsilon-aminocaproic acid (C-3) in acute myocardial infarction
Giornale Italiano di Cardiologia. 1975;5((6):):914-22.
186 out of 391 patients with acute myocardial infarction were treated with C-3 and 205 with placebo in a multicenter, double-blind clinical trial. Ensuing complications were treated in the same way in both groups. C-3 was injected i.v. slowly at the dose of 2 g statim plus 6 g by continuous drip infusion over 24 hrs for 5 days. During treatment, clinical progress was influenced only in regard to cardiac failure since in the C-3 group the improvement was more significant than in the placebo one (P less than 0.0025). Mortality rates were 8.1% and 11.2% for the C-3 and placebo groups, respectively. The difference in mortality was significant (P less than 0.05) for patients treated with C-3 for more than 24 hours. Mortality in male patients treated with C-3 for more than 12 hours was significantly lower (P less than 0.025). In patients less than 60 years old mortality rate was significantly lower (P less than 0.05) and was more so in patients receiving C-3 for more than 12 hours (P less than 0.025). Mortality due to complications was lower in the C-3 group, with arrhythmias (9.8% vs 14.2%), cardiogenic shock (69.2% vs 75%), and cardiac failure (9% vs 19.4%). Results agree with the hypothesis that C-3 may be effective in acute myocardial infarction by improving the action of traditional antiarrhythmic drugs, and augmenting myocardial contraction energy.