Tranexamic acid and bleeding in patients treated with non-vitamin K oral anticoagulants undergoing dental extraction: The EXTRACT-NOAC randomized clinical trial

Abstract

Background Oral bleeding after dental extraction in patients on non-vitamin K oral anticoagulants (NOACs) is a frequent problem. We investigated whether 10% tranexamic acid (TXA) mouthwash decreases post-extraction bleeding in patients treated with NOACs. Methods and findings The EXTRACT-NOAC study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial. Patients were randomly assigned to 10% TXA or placebo mouthwash and were instructed to use the mouthwash prior to dental extraction, for 3 times a day for 3 days thereafter. The primary outcome was the number of patients with any post-extraction oral bleeding up to day 7. Secondary outcomes included the periprocedural, early, and delayed bleeding, and the safety outcomes included all thrombotic events. The first patient was randomized on February 9, 2018 and the last patient on March 12, 2020. Of 222 randomized patients, 218 patients were included in the full analysis set, of which 106 patients were assigned to TXA (74.8 (±8.8) years; 81 men) and 112 to placebo (72.7 (±10.7) years; 64 men). Post-extraction bleeding occurred in 28 (26.4%) patients in the TXA group and in 32 (28.6%) patients in the placebo group (relative risk, 0.92; 95% confidence interval [CI], 0.60 to 1.42; P = 0.72). There were 46 bleeds in the TXA group and 85 bleeds in the placebo group (rate ratio, 0.57; 95% CI, 0.31 to 1.05; P = 0.07). TXA did not reduce the rate of periprocedural bleeding (bleeding score 4 ± 1.78 versus 4 ± 1.82, P = 0.80) and early bleeding (rate ratio, 0.76; 95% CI, 0.42 to 1.37). Delayed bleeding (rate ratio, 0.32; 95% CI, 0.12 to 0.89) and bleeding after multiple extractions (rate ratio, 0.40; 95% CI, 0.20 to 0.78) were lower in the TXA group. One patient in the placebo group had a transient ischemic attack while interrupting the NOAC therapy in preparation for the dental extraction. Two of the study limitations were the premature interruption of the trial following a futility analysis and the assessment of the patients’ compliance that was based on self-reported information during follow-up. Conclusions In patients on NOACs undergoing dental extraction, TXA does not seem to reduce the rate of periprocedural or early postoperative oral bleeding compared to placebo. TXA appears to reduce delayed bleeds and postoperative oral bleeding if multiple teeth are extracted. Trial registration ClinicalTrials.gov NCT03413891 EudraCT; EudraCT number:2017-001426-17; EudraCT Public website: eudract.ema.europa.eu.

Post‐procedural bleeding rate and haemostatic treatment use for dental procedures before and after the implementation of a standardized protocol for people with inherited bleeding disorders

“…We consider this change as beneficial, as previous studies showed that antifibrinolytic drugs in combination with haemostatic treatment are beneficial in preventing perioperative bleeding without increasing the rate of adverse effects in individuals with inherited and acquired bleeding disorders. 18,[26][27][28][29] Moreover, the use of antifibrinolytic drugs such as tranexamic acid is recommended by the World Federation of Hemophilia for invasive dental procedures in persons with haemophilia, as tranexamic acid has the benefits of being administered orally, cheap and safe. 30 The risk-based approach to haemostatic treatment used for the creation of the protocol is in line with the DeBRATT classification.…”

“…We noticed a change in the prescription pattern since the introduction of the protocol, with a significant increase in tranexamic acid administration across several types of bleeding disorders. We consider this change as beneficial, as previous studies showed that antifibrinolytic drugs in combination with haemostatic treatment are beneficial in preventing perioperative bleeding without increasing the rate of adverse effects in individuals with inherited and acquired bleeding disorders 18,26–29 . Moreover, the use of antifibrinolytic drugs such as tranexamic acid is recommended by the World Federation of Hemophilia for invasive dental procedures in persons with haemophilia, as tranexamic acid has the benefits of being administered orally, cheap and safe 30 …”

Tranexamic acid for the prevention and treatment of bleeding in surgery, trauma and bleeding disorders: a narrative review

“…In addition, TXA mouthwash reduced bleeding after dental extraction in patients on vitamin K antagonists and antiplatelet drugs, but there are no studies supporting its use in patients on other types of antithrombotic drugs, except for one. The recent randomized, placebo-controlled, randomized EXTRACT-NOAC trial, indicated that the use of TXA may reduce the risk of delayed bleeding and bleeding with multiple dental extractions in patients treated with non-vitamin K oral anticoagulants [ 148 ].…”

Local Tranexamic Acid for Preventing Hemorrhage in Anticoagulated Patients Undergoing Dental and Minor Oral Procedures: A Systematic Review and Meta-Analysis

“… Risk difference (RD) for postoperative bleeding outcomes across the entire cohort of included patients [ 22 , 23 , 24 , 25 , 26 ]. Heterogeneity: Chi 2 = 9.43, df = 4 ( p = 0.05); I 2 = 58%.…”