Tooth Extraction in Patients With Atrial Fibrillation in Use of New Oral Anticoagulants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of a protocol which does not suspend the new oral anticoagulants (dabigatran, rivaroxaban and apixaban) in front of dental extractions in patients with non-valvular atrial fibrillation.

Detailed Description
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The sample will be divided into three groups according to the pharmacokinetics of the oral anticoagulant: rivaroxaban 1x/day (group 1); dabigatran and apixabana 2x/day (group 2) and warfarin (control group). Extraction of one to three teeth will be scheduled, in the valley of the new oral anticoagulants' concentration, considered the period of smallest haemorrhagic risk without suspension. In group 1 the surgery will be scheduled 14 hours after the last intake, in group 2 the surgery will be scheduled 8 hours after the last intake, while the control group will undergo the procedure with INR values between 2.0 and 3,0. Hemostatic measures with tranexamic acid paste intra alveolar, suture and biological glue GRF® (gelatin, resorcinol and formaldehyde) and post operative care will be associated. The patients will be contacted after the procedure to inform the presence or absence of late bleeding. The patient should return 24 hours later to evaluate the surgical site. This protocol is based on Guidelines and scientific articles, pharmacokinetics and clinical experience of the authors.

Official Title
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Prospective Study of the Assessment of the Dental Protocol for Tooth Extraction in Patients With Atrial Fibrillation in Continuous Use of New Oral Anticoagulants: A Pilot Study

Conditions
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Atrial Fibrillation, Periodontal Disease, Hemorrhage

Intervention / Treatment
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* Drug: Rivaroxaban
* Drug: Dabigatran and Apixaban
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Selection of patients: Both genders, aged over 18 years, regardless of ethnicity, marital status, nationality, naturalness or profession, with non-valvular atrial fibrillation using dabigatran or rivaroxaban or apixaban or warfarin, under medical outpatient treatment or during the hospitalization period. Dentistry: Patients with indications of exodontia of one to three permanent adjacent teeth erupted in the maxilla or mandible due to extensive dental caries or periodontal disease. Exclusion Criteria: Clinical: Patients on concomitant use of antiplatelet agents or heparin, pregnant and lactating patients, with coagulation disorders, severe chronic renal insufficiency (CrCl <30), severe hepatopathies and proven to be allergic to lidocaine and / or epinephrine. Dentistry: Odontophobic, edentulous, or healthy teeth; Deciduous teeth and Included teeth. Regarding the time of medication intake: Regarding the time of medication intake Patients taking rivaroxaban who routinely take the medication between 5:00 a.m. to 4:00 p.m. (unworkable schedule for surgery) that do not accept a change in the intake schedule suggested by the attending physician.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban<br>As the rivaroxaban is ingested 1x/day, the interval between a maximum peak concentration and the other peak is 24 hours. Therefore, the surgery will be performed between two peaks of maximum drug concentration, knowing that the maximum peak concentration is an average of two hours after ingestion. So the surgical procedure should be scheduled 14 hours (2 hours+ 12 hours) after the last medication intake. | Drug: Rivaroxaban<br>* Rivaroxaban 15 or 20mg tablet by mouth, every 24 hours, continuous use.<br>* Other names: Xarelto;|
| Experimental: Dabigatran and Apixaban<br>As dabigatran and apixaban are taken 2x/day, the interval between two peak concentration is 12 hours.Taking into account the first two hours of maximum peak concentration and half the interval between two peaks (2 hours + 6 hours = 8 hours), the surgical procedure must be programmed eight hours after the last intake of medication. | Drug: Dabigatran and Apixaban<br>* Dabigatrana 110 or 150 mg tablet and Apixaban 2,5 or 5mg tablet by mouth, every 12 hours, continuous use.<br>* Other names: Pradaxa and Eliquis;|
| Active Comparator: Warfarin<br>The control group will consist of patients on chronic use of warfarin. The operation will be scheduled at any time, provided that the patient has INR value between 2.0 and 3.0 and test performed in maximum 15 days before surgery. | Drug: Warfarin<br>* The dosage of Warfarin is individualized for each patient, according to the patient's TP/INR value. The value of TP/INR should be in the therapeutic dosage of 2.0 to 3.0<br>* Other names: Marevan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A bleeding event (incidence of postoperative bleeding events) | To evaluate the safety of a protocol regarding the risks of bleeding after dental extractions performed in patients with non-valvular atrial fibrillation in continuous use of the new oral anticoagulants, we compared the incidence of postoperative bleeding events after dental extractions between patients in use of new oral anticoagulants and those treated of warfarin without withdrawal of oral anticoagulant therapy. | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dabigatran, Rivaroxaban, Apixaban, Warfarin, Tooth Extraction