Tranexamic Acid to Reduce Bleeding in Patients Treated With Non-Vitamin K Oral Anticoagulants Undergoing Dental Extraction: The EXTRACT-NOAC Randomized Clinical Trial

Background: Oral bleeding after dental extraction in patients on non-vitamin K oral anticoagulants is a frequent problem. We investigated whether 10% tranexamic acid mouthwash decreases post-extraction bleeding in patients treated with non-vitamin K oral anticoagulants. Methods: The EXTRACT-NOAC study is a randomized, double blind, placebo-controlled, multi-center, clinical trial. Patients were randomly assigned to 10% tranexamic acid or placebo mouthwash, and were instructed to use the mouthwash prior to dental extraction, and three times a day for three days thereafter, and were followed-up for seven days. The primary outcome was the number of patients with any post-extraction oral bleeding up to day 7. Secondary outcomes include the number and type of bleeds and unplanned medical contacts. Findings: 218 patients were included in the full analysis set of which 106 patients were assigned to tranexamic acid (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 tranexamic acid 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 =.72). There were 46 bleeds in the tranexamic acid group and 85 bleeds in the placebo group (rate ratio, 0.57; 95% CI, 0.31 to 1.05; P= .07). Extraction-related bleeds (rate ratio 0.56; 95% CI, 0.32 to 0.96) and delayed bleeds (rate ratio, 0.32; 95% CI, 0.12 to 0.89) were lower in the tranexamic acid group. Patients using tranexamic acid had fewer unplanned medical contacts (rate ratio, 0.39; 95% CI, 0.16 to 0.98). Interpretation: In patients on non-vitamin K oral anticoagulants undergoing dental extracting, tranexamic acid mouthwash did not reduce the number of patients with post-extraction oral bleeding. Tranexamic acid may reduce the number of post-extraction bleeds and unplanned medical contacts. Trial Registration: The trial is registered at ClinicalTrials.gov (Identifier: NCT03413891). Funding Statement: This clinical trial was funded through a grant of the Research Foundation Flanders (Applied Biomedical Research Grant with a Primary Social finality, T002117N) and through a European Thrombosis Investigator Initiated Research Program (ERISTA) grant sponsored by Bristol Myers-Squibb and Pfizer. Declaration of Interests: None of the authors reported a conflict of interest with respect to the EXTRACT-NOAC study. Dr. Verhamme received grants and personal fees from Bayer Healthcare, grants and personal fees from Boehringer Ingelheim, Pfizer, BMS, Daiichi-Sankyo, Leo Pharma, and Portola and Medtronic outside the submitted work. Ethics Approval Statement: The EXTRACT-NOAC study is a prospective, randomized, double blind, placebo-controlled, multicenter, investigator-initiated, clinical trial. The Medical Ethics Committee of University Hospitals Leuven approved the study in July 2017.