Direct-Acting Oral Anticoagulant/Vitamin K Antagonists: Do They Affect the Trabecular and Cortical Structure of the Mandible?

BACKGROUND: This study aimed to evaluate the mandibular bone structure of patients using oral anticoagulants (OACs) vitamin K antagonist drugs (warfarin) and other OACs including direct oral anticoagulants [(DOACs) apixaban, rivaroxaban, dabigatran, edoxaban]. Analyses were based upon the fractal dimension (FD), the panoramic mandibular index (PMI) and the Klemetti index (KI), which is also known as the mandibular cortical index (MCI). METHODOLOGY: Ninety participants were divided into three groups: group 1: 30 systemically healthy individuals who had not used any anticoagulants before, group 2: 30 individuals using warfarin, and group 3: 30 individuals using DOACs. FD was used to analyze trabecular bone architecture in the condyle, angle, and two sites in the alveolar bone. PMI was used to evaluate the quantity of cortical bone and KI was used to evaluate the cortical bone quality. RESULTS: There was no difference between the groups regarding FD analysis and KI; however, a difference was found between groups 1, 2, and 3 in the PMI (P≤ 0.001). The PMI in group 1 was higher than in groups 2 and 3. CONCLUSION: Mandibular radiomorphometric indices can be used on panoramic radiographs to evaluate the quantity of mandibular cortical bone in patients using oral anticoagulants.

Perioperative Management of Patients Taking Direct Oral Anticoagulants: A Review.

Importance: Direct oral anticoagulants (DOACs), comprising apixaban, rivaroxaban, edoxaban, and dabigatran, are commonly used medications to treat patients with atrial fibrillation and venous thromboembolism. Decisions about how to manage DOACs in patients undergoing a surgical or nonsurgical procedure are important to decrease the risks of bleeding and thromboembolism. Observations: For elective surgical or nonsurgical procedures, a standardized approach to perioperative DOAC management involves classifying the risk of procedure-related bleeding as minimal (eg, minor dental or skin procedures), low to moderate (eg, cholecystectomy, inguinal hernia repair), or high risk (eg, major cancer or joint replacement procedures). For patients undergoing minimal bleeding risk procedures, DOACs may be continued, or if there is concern about excessive bleeding, DOACs may be discontinued on the day of the procedure. Patients undergoing a low to moderate bleeding risk procedure should typically discontinue DOACs 1 day before the operation and restart DOACs 1 day after. Patients undergoing a high bleeding risk procedure should stop DOACs 2 days prior to the operation and restart DOACs 2 days after. With this perioperative DOAC management strategy, rates of thromboembolism (0.2%-0.4%) and major bleeding (1%-2%) are low and delays or cancellations of surgical and nonsurgical procedures are infrequent. Patients taking DOACs who need emergent (<6 hours after presentation) or urgent surgical procedures (6-24 hours after presentation) experience bleeding rates up to 23% and thromboembolism as high as 11%. Laboratory testing to measure preoperative DOAC levels may be useful to determine whether patients should receive a DOAC reversal agent (eg, prothrombin complex concentrates, idarucizumab, or andexanet-α) prior to an emergent or urgent procedure. Conclusions and Relevance: When patients who are taking a DOAC require an elective surgical or nonsurgical procedure, standardized management protocols can be applied that do not require testing DOAC levels or heparin bridging. When patients taking a DOAC require an emergent, urgent, or semiurgent surgical procedure, anticoagulant reversal agents may be appropriate when DOAC levels are elevated or not available.

Effect of different anticoagulants and antiplatelets on intraoral bleeding time during professional oral hygiene session.

OBJECTIVE: Patients with thromboembolic problems, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to examine the bleeding durations associated with various anticoagulants and antiplatelets during professional dental hygiene sessions, utilizing a modified Ivy test adapted for the oral context. MATERIALS AND METHODS: Ninety-three consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn's post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; RESULTS: Control patients presented the lowest bleeding time 50 s, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p = 0.004), VKA (p < 0.001), DAPT (p < 0.001). CONCLUSIONS: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT. CLINICAL SIGNIFICANCE: bleeding did not interfere with the oral hygiene session The optimal period for dental treatment of these patients should be 2-3 h before the next dose, without the need to temporarily suspend the medication.

Assessment of the Potential for Veverimer Drug-Drug Interactions.

Veverimer is a polymer being developed as a potential treatment of metabolic acidosis in patients with chronic kidney disease. Veverimer selectively binds and removes hydrochloric acid from the gastrointestinal tract, resulting in an increase in serum bicarbonate. Veverimer is not systemically absorbed, so potential drug-drug interactions (DDIs) are limited to effects on the absorption of other oral drugs through binding to veverimer in the gastrointestinal tract or increases in gastric pH caused by veverimer binding to hydrochloric acid. In in vitro binding experiments using a panel of 16 test drugs, no positively charged, neutral, or zwitterionic drugs bound to veverimer. Three negatively charged drugs (furosemide, aspirin, ethacrynic acid) bound to veverimer; however, this binding was reduced or eliminated in the presence of normal physiologic concentrations (100-170 mM) of chloride. Veverimer increased gastric pH in vivo by 1.5-3 pH units. This pH elevation peaked within 1 hour and had returned to baseline after 1.5-3 hours. Omeprazole did not alter the effect of veverimer on gastric pH. The clinical relevance of in vitro binding and the transient increase in gastric pH was evaluated in human DDI studies using two drugs with the most binding to veverimer (furosemide, aspirin) and two additional drugs with pH-dependent solubility effecting absorption (dabigatran, warfarin). None of the four drugs showed clinically meaningful DDI with veverimer in human studies. Based on the physicochemical characteristics of veverimer and results from in vitro and human studies, veverimer is unlikely to have significant DDIs. SIGNIFICANCE STATEMENT: Patients with chronic kidney disease, who are usually on many drugs, are vulnerable to drug-drug interactions (DDIs). The potential for DDIs with veverimer was evaluated based on the known site of action and physicochemical structure of the polymer, which restricts the compound to the gastrointestinal tract. Based on the findings from in vitro and human studies, we conclude that veverimer is unlikely to have clinically significant DDIs.

Dental implant surgery in patients in treatment by dabigatran.

OBJECTIVES: The aim of this study was to evaluate the incidence of bleeding complications after dental implant placement in patients in treatment by the oral anticoagulant dabigatran following a specific protocol. MATERIAL AND METHODS: Seventy-one patients were divided into two groups: 29 had been taking dabigatran for over 6 months (150 mg orally every 12 h) before implant surgery (dabigatran group) and a control group consisting of 42 healthy subjects. Patients were treated in an outpatient setting. All subjects received dental implants in different positions, dabigatran group patients 12 h after the last dose of dabigatran. Nonabsorbable sutures were used and patients were given gauzes impregnated with tranexamic acid 5% to bite on for 30-60 min. Dabigatran patients resumed medication 8 h after the procedure, resuming usual dosage (every 12 h) the day after surgery. RESULTS: Two dabigatran patients and two control patients presented slight bleeding the day after surgery. Bleeding was managed with gauzes impregnated with tranexamic acid. No statistically significant differences (P = 0.542) were found in relation to bleeding episodes between the groups, with a relative risk of 0.675 based on the pooled groups and a 95% confidence interval of 0.090-5.088. CONCLUSIONS: Dental implant surgery in patients taking dabigatran can be performed safely providing 12 h have passed since the last dose and local hemostatic measures are applied. Normal dosage can be resumed 8 h after implant surgery.

Management of dental patients taking direct oral anticoagulants: Dabigatran.

Direct oral anticoagulants (DOACs) are increasingly used as alternatives to warfarin because of the superior pharmacokinetic properties. Clinical guidelines on the influences of DOACs for dental procedures have emerged, but all of necessity based on low-quality available evidence. Herein, we share our experience with a case series, and propose a protocol regarding the management of dental patients taking DOACs.

Review: An overview and analysis of novel oral anticoagulants and their dental implications.

BACKGROUND: Dabigatran, rivaroxaban, apixaban and edoxaban are approved novel oral anticoagulants (NOACs) as alternatives to Vitamin K antagonists (VKA). Physicians are prescribing an ever-increasing amount these drugs to their patients due to various advantages over existing medications. AIMS: The objective of this review is to provide the dental professional with current literature surrounding the emergence of NOACs, as well as various case studies on the subject, in an effort to guide clinical decision making regarding these medications. The pharmacological profiles of these NOACs and idarucizumab, a reversal agent for dabigatran, will be detailed in this review. MATERIALS AND METHODS: A review of the literature on NOACs was undertaken and the Pubmed, Medline, and Embase databases were used to identify articles published in the English language. Additionally, major dental medicine journals were hand searched, followed by a review of the ClinicalTrials.gov database. RESULTS: Due to minimal research regarding dental treatment of patients on NOACs and minimal clinical experience of practitioners treating these patients, there is currently insufficient data to establish an evidence-based NOAC management protocol in a dental setting. DISCUSSION: In this review, the most significant advantages of NOACs over VKAs was found to be limited interactions with other drugs as well as rapid onset and offset of action. CONCLUSION: Despite these benefits, as well as various others, NOACs still lack specific management parameters as well as antidotes or reversal agents. Therefore, dental professionals must use caution when treating patients currently taking these specific anticoagulants.

Prognostic Value of Red Blood Cell Distribution Width on Bleeding Events in Nonvalvular Atrial Fibrillation Patients Taking Dabigatran (110 mg b.i.d.) after Catheter Ablation.

OBJECTIVES: Recent research has indicated that red blood cell distribution width (RDW) is associated with the prognosis of cardiovascular diseases such as chronic heart failure and coronary heart disease. We aimed to study the predictive value of RDW for bleeding events in patients with nonvalvular atrial fibrillation (NVAF) during the administration of 110 mg of dabigatran twice a day after catheter ablation. METHODS: One hundred and seventy-two NVAF patients who were hospitalized and received catheter ablation in Jiangsu Provincial People's Hospital from January 2014 to January 2015 were enrolled (110 mg of dabigatran was administered orally to outpatients preoperatively twice a day for 3 weeks). The enrolled patients were divided into the high RDW (>12.8%) group (n = 85) and the low RDW (≤12.8%) group (n = 87) according to the median RDW. The activated partial thromboplastin time (APTT) at dabigatran trough concentration was also detected. Patients were followed up for 3 months to observe the occurrence of bleeding events, and the predictive value of RDW as well as APTT for bleeding events was assessed from receiver-operating characteristic (ROC) analyses. RESULTS: In all patients, preoperatively, no bleeding events were observed and the APTT did not exceed twice the normal upper limit. Thirteen cases of bleeding events, all minor bleeding, occurred after a 3-month follow-up: 3 of gingival bleeding, 3 of urinary tract bleeding, 3 conjunctival hemorrhages and 4 subcutaneous hemorrhages. The incidence of bleeding events in the low RDW group was lower than in the high RDW group (3.4 vs. 11.8%, p = 0.039). The areas under the ROC curve for RDW and APTT to predict the occurrence of bleeding events were 0.737 (cutoff point 13.25%; p < 0.05) and 0.558 (p > 0.05), respectively. CONCLUSION: RDW was associated with the occurrence of bleeding events in NVAF patients on dabigatran (110 mg twice a day) after ablation, while also being an independent predictor of bleeding events. RDW had superior predictive value for bleeding events over APTT when APTT did not exceed twice the normal upper limit.

Improved oral bioavailability and therapeutic efficacy of dabigatran etexilate via Soluplus-TPGS binary mixed micelles system.

The clinical use of dabigatran etexilate (DABE) is limited by its poor absorption and relatively low bioavailability. Our study aimed to explore the potential of a mixed micelle system composed of Soluplus® and D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral absorption and bioavailability of DBAE. DBAE was first encapsulated into Soluplus/TPGS mixed micelles by a simple thin film hydration method. The DBAE loaded micelles displayed an average size distribution of around 83.13 nm. The cellular uptake of DBAE loaded micelles in Caco-2 cell monolayer was significantly enhanced by 2-2.6 fold over time as compared with DBAE suspension. Both lipid raft/caveolae and macropinocytosis-mediated the cell uptake of DBAE loaded micelles through P-glycoprotein (P-gp)-independent pathway. Compared with the DBAE suspension, the intestinal absorption of DBAE from DBAE mixed micelles in rats was significantly improved by 8 and 5-fold in ileum at 2 h and 4 h, respectively. Moreover, DBAE mixed micelles were absorbed into systemic circulation via both portal vein and lymphatic pathway. The oral bioavailability of DBAE mixed micelles in rats was 3.37 fold higher than that of DBAE suspension. DBAE mixed micelles exhibited a comparable anti-thrombolytic activity with a thrombosis inhibition rate of 63.18% compared with DBAE suspension in vivo. Thus, our study provides a promising drug delivery system to enhance the oral bioavailability and therapeutic efficacy of DBAE.

Managing patients taking novel oral anticoagulants (NOAs) in dentistry: a discussion paper on clinical implications.

BACKGROUND: The aim of this paper is to contribute to the discussion on how to approach patients taking new orally administered anticoagulants (NOAs) dabigatran etexilate (a direct thrombin inhibitor), rivaroxaban and apixaban (factor Xa inhibitors), before, during and after dental treatment in light of the more recent knowledges. DISCUSSION: In dentistry and oral surgery, the major concerns in treatment of patients taking direct thrombin inhibitors and factor Xa inhibitors is the risk of haemorrhage and the absence of a specific reversal agent. The degree of renal function, the complexity of the surgical procedure and the patient's risk of bleeding due to other concomitant causes, are the most important factors to consider during surgical dental treatment of patients taking NOAs. For patients requiring simple dental extraction or minor oral surgery procedures, interruption of NOA is not generally necessary, while an higher control of bleeding and discontinuation of the drug (at least 24 h) should be requested before invasive surgical procedures, depending on renal functionality. The clinician has to consider that the number of patients taking NOAs is rapidly increasing. Since available data are not sufficient to establish an evidence-based dental management, the dentist must use caution and attention when treating patients taking dabigatran, rivaroxaban and apixaban.

Dabigatran: A new oral anticoagulant. Guidelines to follow in oral surgery procedures. A systematic review of the literature.

BACKGROUND: Dabigatran is a newly commercialized drug that is replacing other anticoagulants in the prevention of venous thromboembolism, stroke and systemic arterial valve embolism. It acts directly on thrombin presenting in a dynamic and predictable way, which does not require monitoring these patients. Therefore, we consider the need to assess whether their use increases the risk of bleeding involved before any dental treatment. MATERIAL AND METHODS: We performed a systematic review with a bibliographic search in PubMed/Medline along with the Cochrane Library. We excluded articles dealing with all anticoagulants other than dabigatran, and works about surgical treatments in anatomical locations other than the oral cavity. RESULTS: We included a total of 13 papers of which 1 was a randomized clinical trial, 9 narrative literature reviews, 1 case series, 2 clinical cases and 1 expert opinion. Because we did not obtain any properly designed clinical trials, we were unable to conduct a meta-analysis. CONCLUSIONS: Currently, there is no consensus on the procedure to be followed in patients taking dabigatran. However, all authors agree to treat each case individually in accordance to the risk of embolism, postoperative bleeding and renal function. Also, it is necessary to perform minimally invasive interventions, and take the appropriate local anti-hemolytic measures.

Managing dentoalveolar surgical procedures in patients taking new oral anticoagulants.

The development of new orally administered anticoagulants, such as dabigatran, rivaroxaban, and apixaban, in the past few years has focused on avoiding some of the drawbacks associated with warfarin. This work aims to illustrate the main features of the most commonly used new oral anticoagulants, reviewing the current literature on the management of patients taking these drugs and needing oral and implant surgery, and discussing the currently proposed related guidelines.

Haemostasis. Part 2: Medications that affect haemostasis.

Post-operative haemorrhage is a recognized complication in dental practice. This may be more prevalent in patients taking antithrombotic medications. It is important that the dentist understands the mechanism of action of these drugs and how they may affect management of dental patients. Clinical Relevance: Dental professionals must be aware of those medications affecting haemostasis and how they may impact on management. The emergence of different therapeutic regimens has increased the number of such drugs.

Dental implications of new oral anticoagulants for atrial fibrillation.

UNLABELLED: As dental professionals, we should all be familiar with the most common oral anticoagulant, warfarin, and how to manage our patients that are taking it. However, several new oral anticoagulants which have recently been approved by the National Institute for Health and Care Excellence (NICE) are now being prescribed for patients in the United Kingdom. These new oral anticoagulants fall into two different categories: a direct thrombin inhibitor dabigatran etexilate (Pradaxa Boehringer-Ingelheim, Bracknell, Berkshire) and activated Factor X inhibitors rivaroxaban (Xarelto Bayer HealthCare, Newbury, Berkshire) and apixaban (Eliquis Bristol-Myers Squibb, Uxbridge, Middlesex). These new drugs will have potential consequences for how dental practitioners manage patients requiring dental treatment, especially extractions and minor surgical procedures. CLINICAL RELEVANCE: It is important that dentists are aware of new anticoagulants which are being prescribed for patients to ensure that they receive safe and appropriate dental treatment. As healthcare professionals we should also be aware of how and when to report adverse drug reactions.

New oral anticoagulants and their implications for dental patients.

Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. Over the last 40 years, warfarin has been the oral anticoagulant of choice and has been considered the mainstay of treatment. However, its use is limited by a narrow therapeutic index and complex pharmacodynamics, necessitating regular monitoring and dose adjustments. Recently, two new oral anticoagulants--dabigatran etexilate (a direct thrombin inhibitor) and rivaroxiban (a factor Xa inhibitor)--have been approved for use in North America and Europe. Unlike warfarin, dabigatran and rivaroxiban are relatively small molecules that work as anticoagulants by targeting specific single steps of the coagulation cascade. Their advantages, relative to warfarin, include: predictable pharmacokinetics; limited food and drug interactions; rapid onset of action; and, short half-life. They require no monitoring. However, they lack a specific reversal agent. The number of patients taking dabigatran and rivaroxaban is increasing. Therefore, it is inevitable that dentists will be required to perform invasive procedures on this cohort of patients. This paper outlines the various properties of the new oral anticoagulants and the most recent guidelines regarding the management of these dental patients taking these medications.

Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial.

BACKGROUND: Dabigatran reduces ischemic stroke in comparison with warfarin; however, given the lack of antidote, there is concern that it might increase bleeding when surgery or invasive procedures are required. METHODS AND RESULTS: The current analysis was undertaken to compare the periprocedural bleeding risk of patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial treated with dabigatran and warfarin. Bleeding rates were evaluated from 7 days before until 30 days after invasive procedures, considering only the first procedure for each patient. A total of 4591 patients underwent at least 1 invasive procedure: 24.7% of patients received dabigatran 110 mg, 25.4% received dabigatran 150 mg, and 25.9% received warfarin, P=0.34. Procedures included: pacemaker/defibrillator insertion (10.3%), dental procedures (10.0%), diagnostic procedures (10.0%), cataract removal (9.3%), colonoscopy (8.6%), and joint replacement (6.2%). Among patients assigned to either dabigatran dose, the last dose of study drug was given 49 (35-85) hours before the procedure on comparison with 114 (87-144) hours in patients receiving warfarin, P<0.001. There was no significant difference in the rates of periprocedural major bleeding between patients receiving dabigatran 110 mg (3.8%) or dabigatran 150 mg (5.1%) or warfarin (4.6%); dabigatran 110 mg versus warfarin: relative risk, 0.83; 95% CI, 0.59 to 1.17; P=0.28; dabigatran 150 mg versus warfarin: relative risk, 1.09; 95% CI, 0.80 to 1.49; P=0.58. Among patients having urgent surgery, major bleeding occurred in 17.8% with dabigatran 110 mg, 17.7% with dabigatran 150 mg, and 21.6% with warfarin: dabigatran 110 mg; relative risk, 0.82; 95% CI, 0.48 to 1.41; P=0.47; dabigatran 150 mg: relative risk, 0.82; 95% CI, 0.50 to 1.35; P=0.44. CONCLUSIONS: Dabigatran and warfarin were associated with similar rates of periprocedural bleeding, including patients having urgent surgery. Dabigatran facilitated a shorter interruption of oral anticoagulation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Implications of Dabigatran, a direct thrombin inhibitor, for oral surgery practice.

Direct thrombin inhibitors, specifically orally administered dabigatran etexilate, are emerging as alternatives to warfarin for anticoagulation in the management of atrial fibrillation and venous thromboembolism. The risk associated with bleeding events while taking dabigatran has been documented in multiple randomized controlled trials, but to date, no studies have focused on the risk of bleeding after dental extraction. Extraction of teeth is one of the most common surgical procedures and may cause significant bleeding, so a thorough understanding of the pharmacology of anticoagulant medications is required to prevent complications. With the increasing use of direct thrombin inhibitors, the safe management of patients taking these anticoagulants must be delineated. This review compares dabigatran and warfarin, especially in terms of their effects on dental and oral surgery practice, and examines best management of these patients in light of the existing literature.

Frequency of hemorrhage after tooth extraction in patients treated with a direct oral anticoagulant: A multicenter cross-sectional study.

OBJECTIVE: Few studies have compared the frequency of hemorrhages after tooth extraction between patients taking direct oral anticoagulants (DOACs) and those taking warfarin or no anticoagulants. Further, the effects of the timing of DOAC administration and tooth extraction on the frequency of post-extraction hemorrhage have not been demonstrated. Therefore, we compared the frequency of post-extraction hemorrhages in patients in these different conditions and examined the effects of the timing of DOAC administration and tooth extraction on the frequency. DESIGN: Prospective multicenter study. SETTING: Eighty-six Japanese hospitals. PARTICIPANTS: In total, 182 teeth extracted from 145 individuals (119 teeth from adult males) receiving dabigatran and 88 teeth from individuals (62 teeth from adult males) receiving rivaroxaban were included. INTERVENTION: Tooth extraction was followed by a 7-day observational period between November 1, 2008 and December 31, 2015. Dabigatran was administered twice daily; rivaroxaban was administered once a day. PRIMARY OUTCOME MEASURE: Hemorrhage after tooth extraction. RESULTS: The frequency of hemorrhage after tooth extraction was 1.65%, 3.41%, and 3.63% in those treated with dabigatran, rivaroxaban, and warfarin, respectively, and 0.39% in those who did not receive anticoagulants. Hemorrhages after tooth extraction were significantly higher in the rivaroxaban group than in patients who did not receive anticoagulants (P = 0.008). These frequencies did not differ significantly in the dabigatran and rivaroxaban groups compared to the warfarin group (P = 0.221 and P = 1.000, respectively). CONCLUSIONS: The frequency of hemorrhaging after tooth extraction appeared to be similar in patients receiving continuous dabigatran or rivaroxaban and in those receiving continuous warfarin.

Real-life data of major and minor bleeding events with direct oral anticoagulants in the one-year follow-up period: The NOAC-TURK study.

OBJECTIVE: This study aimed to evaluate the safety of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) during daily clinical practice. METHODS: This was a prospective study conducted between January 01, 2016, and April 01, 2017, in patients aged ≥18 years with a diagnosis of NVAF. We performed the study in 9 clinical centers from different regions of Turkey, and the mean follow-up period was 12+2 months. We investigated major and minor bleeding events of DOAC. RESULTS: A total of 1807 patients with NVAF were enrolled. The mean age of the patients was 73.6±10.2 years, CHA2DS2-VASc score was 3.6±1.4, and HAS-BLED score was 2±1.2. The most frequently prescribed DOAC was dabigatran 110 mg bid in 409 (22.6%) patients. The patients on apixaban 2.5 mg bid were older (p<0.001). Patients on rivaroxaban 15 mg od also had a higher prevalence of chronic renal failure, 46 (16.7%) patients. A total of 205 (11.4%) bleeding events were observed; among these, 34 (1.9%) patients had major bleeding and 171 (9.4%) patients had minor bleeding. The major and minor bleeding events were 2/273 (0.7%) and 30/273 (10.9%) in patients receiving dabigatran 150 mg bid, 13/409 (3%) and 44/409 (10.7%) in patients receiving dabigatran 110 mg bid, 4/385 (1%) and 42/385 (10.9%) in patients receiving rivaroxaban 20 mg od, 8/276 (2.9%) and 27/276 (9.7%) in patients receiving rivaroxaban 15 mg od, 3/308 (0.9%) and 14/308 (4.5%) in patients receiving apixaban 5 mg bid, 4/156 (2.5%) and 14/156 (9%) in patients receiving apixaban 2.5 mg bid, respectively. The total bleeding events were 17 (5.6%) in patients receiving apixaban 5 mg, less than those receiving other DOACs. On multivariate analyses, rivaroxaban 20 mg od (p=0.002), ATRIA and HAS-BLED scores, and peripheral artery disease were independent indicators of bleeding. The most frequent location of major bleeding was the gastrointestinal system (GIS) [17 (0.9%) patients], and the most frequent location of minor bleeding was the gingiva [45 (2.5%) patients]. CONCLUSION: This study showed that similar results as the previous real-life study; however, we had some different results, such as the GIS tract bleeding was more frequent in patients receiving dabigatran 110 mg bid. The major and intracranial bleeding events were similar for different DOACs; and among DOACs, only rivaroxaban 20 mg od was associated with a high risk of bleeding.