Abstract: No eligible trials in people on continuous treatment with DOACs undergoing oral or dental procedures were identified. Three randomised trials and one quasi-randomised trial (follow-up in all was seven days) in people on continuous treatment with VKAs were included with a total of 253 participants (mean age 60 years). Two trials published in 1989 and 1993 compared the antifibrinolytic agent TXA with placebo in people using VKAs. Two other trials were published in 1999 and 2015 and compared TXA with gelatin sponge and sutures, and dry gauze compression, respectively. In all included trials, those who were treated with VKAs had international normalised ratio (INR) values within the therapeutic range and TXA was applied locally, not systemically. The two trials from 1989 and 1993 comparing TXA with placebo showed a statistically significant beneficial effect regarding the number of major postoperative bleeding episodes requiring intervention, with a pooled risk difference (RD) of -0.25 (95% confidence interval (CI) -0.36 to -0.14) (128 participants) (moderate-quality evidence). For the two trials that compared TXA with either gelatin sponge and sutures or with dry gauze compression, there was no difference between the TXA and the standard care group, RD 0.02 (95% CI -0.07 to 0.11) (125 participants) (moderate-quality evidence). The combined RD of all included trials was -0.13 (95% CI -0.30 to 0.05) (moderate-quality evidence). There were no side effects of antifibrinolytic therapy that required treatment withdrawal (128 participants) (moderate-quality evidence). Despite heterogeneity between trials with respect to the different haemostatic measures used in the control groups, the trials were comparable regarding design and baseline participant characteristics. Overall, we considered the risk of bias to be low in the trials comparing TXA with placebo and moderate in the trials comparing TXA with alternative haemostatic measures. Based on the results of this Cochrane Review, there seems to be a beneficial effect of locally applied TXA in preventing oral bleeding in people on continuous treatment with VKAs undergoing minor oral surgery or dental extractions. However, the small number of identified randomised controlled trials, the relatively small number of participants included in the trials and the differences in standard therapy and treatment regimens between trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in this population. We were unable to identify any eligible trials in people on continuous treatment with DOACs undergoing oral or dental procedures. Therefore, a beneficial effect of antifibrinolytic therapy can currently only be assumed based on data from the people using VKAs.

Plain-language summary: We did not find any trials of antifibrinolytic medicine for preventing bleeding after minor oral surgery or dental extractions in people using DOACs. This review includes four trials (253 participants) in people continuously treated with VKAs during minor oral surgery or dental extractions. The earliest included trial was published in 1989 and the most recent one in 2015. The mean age of all participants was 60 years. The follow-up time in all trials was seven days. Overall, the included trials showed a reduction in the number of bleeds after dental extraction when using tranexamic acid solution in the mouth. Combining the results of the separate trials it appeared that antifibrinolytic medication reduces the bleeding rate after dental extractions by 25% when compared to placebo ('dummy' treatment). However, there was no difference in bleeding rate between people treated with tranexamic acid and those treated with standard care (e.g. gauze compression or stitches). Side effects of the antifibrinolytic medication rarely occurred and did not lead to individuals discontinuing tranexamic acid treatment. No evidence was found for people being treated with DOACs. It could, however, be argued that, if antifibrinolytic medicine is effective in people on continuous treatment with VKAs, it might also work for people receiving other comparable anticoagulant drugs. In relation to the review's two primary outcomes of number of postoperative bleeds and side effects of therapy, we judged there to be moderate-quality evidence. In the two trials comparing tranexamic acid with placebo, the risk of bias, in relation to trial design, was considered to be low, in the two trials comparing tranexamic acid to standard care (gelatin sponge and sutures; or dry gauze compression) the risk of bias was considered to be moderate. This was mainly due to the lack of blinding (a way of making sure that the people involved in the trial do not know which trial arm they are assigned to) and inadequate allocation concealment (using the play of chance to assign participants to comparison groups to prevent selection bias) in two of these trials. There were differences between the trials with regards to different standard care treatments.