ABC | Volume 111, Nº3, September 2018

Original Article Andrade et al Anticoagulation and dental procedure Arq Bras Cardiol. 2018; 111(3):394-399 Dabigatran etexilate, an oral direct thrombin inhibitor, has a serum half-life of 12 to 17 hours and requires no INR monitoring. In the RE-LY trial, 5 which proved the non-inferiority and efficacy of that NOAC as compared to warfarin, 10% of the study participants needed to undergo dental procedures. 5 The RE-LY trial subgroups (dabigatran and warfarin) have shown similar periprocedural bleeding rates, with greater benefits for the dabigatran group regarding major bleedings because of the faster reversion of the drug’s effect. Therefore, dabigatran has emerged as an alternative to warfarin for anticoagulation in the treatment of AF and venous thromboembolism. 6 Several guidelines have validated the use of warfarin or any NOAC (class of recommendation I, level of evidence A) for patients with nonvalvular AF and indication for antithrombotic therapy; however, NOACs are not indicated to patients with mechanical prosthetic valve or hemodynamically significant mitral stenosis, because such patients have been excluded from the major studies on NOACs in AF. 7 Cardiologists are often sought for guidance regarding the suspension of anticoagulants before a dental procedure, because of the concern with bleeding. In addition, dentists should be aware of the NOACs prescribed, as well as of their peculiarities, to ensure that patients receive safe and proper dental treatment. 8 The risk for hemorrhagic events associated with the use of NOACs has been documented in several randomized clinical trials, but no large study has assessed specifically the risk for bleeding after a dental extraction or other dental procedure involving bleeding. Dental extraction is one of the most common surgical procedures and can cause significant bleeding. With the increasing use of direct thrombin inhibitors in clinical practice, the occurrence of bleeding and hemorrhagic complications in that context requires better assessment. 9 The present study aimed at assessing the severity of bleeding associated with the use of dabigatran as compared to traditional oral anticoagulation (warfarin) in individuals undergoing dental procedures. Methods and Sample Selection This is a prospective single-center controlled study with one single observer. Patients diagnosed with nonvalvular AF and indication for anticoagulation, cared for at a cardiology referral center, and requiring single or multiple dental extractions were included. All patients provided written informed consent, and the study protocol was approved by the Ethics Committee in Research of the institution. The patients were followed up by a clinical cardiologist in two groups: group 1, warfarin (25); group 2, dabigatran (12). Patients, independently of sex, aged 18 years or older, with nonvalvular AF and on an oral anticoagulant (warfarin) or NOAC (dabigatran) were selected. Those on oral dabigatran at the dose of 150mg every 12 hours received the drug from the Municipal Health Department. Dabigatran was specifically chosen because of a previously established care partnership between the Municipal Health Department and Boehringer Ingelheim’s laboratories for anticoagulation of patients with nonvalvular AF. Individuals with the following characteristics were excluded: contraindication for anticoagulation; refusal to provide written informed consent; use of warfarin with an INR outside the therapeutic range (2.0 – 3.0) on the day of the dental procedure. Before the procedure, the patients’ vital data, such as systemic blood pressure and heart rate, as well as their weight and height were assessed. In addition, the patients were asked about their race (white, mixed or black), educational level and family income. Those of the warfarin group underwent blood collection to measure PT and INR before the procedure (same day) by use of hemostasis screening tests, while those of the dabigatran group took the predicted dose (150 mg every 12 hours). Patients received prophylaxis for infectious endocarditis, when indicated, in accordance with current guidelines. The dental extractions were performed according to the department’s protocol for dental treatment of patients with heart diseases on anticoagulants. The local hemostatic measures comprised appropriate sutures, cellulose sponge and tranexamic acid (ground pill). All patients were prescribed dipyrone, 1 g up to every 6 hours for pain after the procedure, or, in case of allergy to dipyrone, paracetamol, 750mg up to every 6 hours. Bleedings or hemorrhagic complications of the patients on oral anticoagulants were assessed by the surgical dentist (single observer) during and after the single or multiple dental extractions. Primary outcome was defined as bleeding time 1, between the beginning of suture and complete hemostasis. The following outcomes were also assessed: bleeding time 2 (between the end of suture and complete hemostasis), bleeding before dental extraction, bleeding during dental extraction, and bleeding 24 hours, 48 hours and 7 days after the procedure. The bleeding scale was used, and major bleedings were those from 2.1 on, as described by Iwabuchi et al. (Figure 1). 10 Data analysis Statistical analysis The Statistical Package for Social Sciences (SPSS), version 15, was used for data analysis. Nonparametric tests were used for the analysis of continuous variables, because of the small sample size and the well-known low performance of the tests of adherence to normality in small samples. Continuous variables were described as median and interquartile range (IQR). Categorical variables were described as relative frequency and compared by use of Chi-square and Fisher exact tests. Continuous variables were compared by use of Wilcoxon test for dependent samples, while Mann-Whitney U test was used for independent samples. Statistical significance was defined as p value < 0.05. Sample size calculation The sample size was calculated to yield statistical power of 80% and an alpha of 5%, estimating, based on previous clinical experience, a total bleeding time around 180 ± 60 seconds for the warfarin group, and expecting a reduction of at least 60 seconds in the dabigatran group as compared to the warfarin group. Thus, the sample size calculated was 12 patients in each group. Because the inclusion of patients in the warfarin group was easy, its sample size was doubled. 395