Oral Anticoagulant and Antiplatelet Medications and Dental Procedures

Oral anticoagulant and antiplatelet agents are prescribed for individuals who are at high risk for or who have had thromboembolic events (e.g., blood clots).  These include patients who have experienced deep-vein thrombosis (DVT) or pulmonary embolism (PE) or who have nonvalvular atrial fibrillation (NVAF), a cardiac arrhythmia that predisposes patients to clot formation.  Oral anticoagulants include the vitamin K antagonist warfarin (Coumadin®) and the newer direct-acting agents, including the direct thrombin inhibitor dabigatran (Pradaxa®) and the factor Xa inhibitors apixaban (Eliquis®), rivaroxaban (Xarelto®), and edoxaban (Savaysa® [Lixiana® in the European Union, Japan, and others]).^1-6 Oral antiplatelet agents include clopidogrel (Plavix®), ticlopidine (Ticlid®), prasugrel (Effient®), ticagrelor (Brilinta®), and/or aspirin.⁷  Adverse effects associated with these drugs can include prolonged bleeding or bruising.

Without the anticoagulant/antiplatelet medications, these patients are at higher risk for blood clot development, which could result in thromboembolism, stroke, or myocardial infarction (MI). The serious risks of stopping or reducing these medication regimens need to be balanced against the potential consequences of prolonged bleeding,^8-12 which can be controlled with local measures such as mechanical pressure, hemostatic agents (e.g., Gelfoam® or Surgicel®), suturing, and/or antifibrinolytics, such as tranexamic acid.^13-20 The following sections review the evidence on management of patients taking these drugs and undergoing dental procedures.

Four direct-acting oral anticoagulants have been approved for marketing in the U.S. for use in patients to prevent or treat DVT and PE, or reduce the risk of stroke and systemic embolism in patients with NVAF. These are dabigatran (Pradaxa®), apixaban (Eliquis®), rivaroxaban (Xarelto®), and edoxaban (Savaysa® [Lixiana® in the European Union, Japan, and others]).^1-4 These agents differ from traditional oral anticoagulant therapy (i.e., warfarin) in that they are targeted in action; are given as fixed doses; have more predictable pharmacokinetics and shorter half-lives; require little to no routine monitoring; and have fewer drug or food interactions.²¹

There is no direct evidence from prospective trials comparing different periprocedural management strategies for dental patients receiving the target-specific oral anticoagulants and evaluating effects on patient outcomes. However, based on limited evidence as reviewed in the following sections, in most cases, there is no need to alter the anticoagulation regimen prior to most dental interventions.^{18, 22-26}

A 2015 consensus guideline from the European Heart Rhythm Association^{27, 28} (updating a 2013 guideline²⁹) suggests that interventions not necessarily requiring discontinuation of the newer anticoagulants include extraction of 1 to 3 teeth; periodontal surgery; abscess incision; or implant positioning.

A 2019 systematic review and meta-analysis on direct oral anticoagulant management for invasive oral procedures by Manfredi et al.³⁰ included 21 papers in their review; no randomized, controlled trials were found. Six studies that were included in the meta-analysis reported direct comparisons of continued versus discontinued direct oral anticoagulant therapy prior to dental procedures. The authors reported no discernable important differences in postoperative bleeding events between people who continued versus discontinued direct oral anticoagulation therapy; however, they cautioned that the results should be interpreted with caution because of the low quality of the evidence and the small number of participants included in the studies.

A 2018 systematic review³¹ looked at the question of how to safely manage direct-acting oral anticoagulants in patients requiring dental procedures with low-to-moderate risk of bleeding. Procedures that were defined as being low risk were administration of local anesthetic, simple restorations, supragingival scaling, and single tooth extraction; procedures considered moderate risk were extractions of 2 to 4 teeth and local gingival surgery of 5 or fewer teeth. Five papers were included in the review of evidence. Among patients receiving the direct-acting anticoagulants and undergoing dental procedures associated with low-to-moderate bleeding risk, bleeding rates were low whether the anticoagulant was continued or held periprocedurally. Bleeding that was documented was generally mild and controlled by local hemostatic measures.

Two narrative reviews published in 2015^{13, 32} included suggestions regarding more conservative approaches that might be considered, such as maximizing the time between the last dose of the anticoagulant and the dental intervention, especially in patients who may have higher risk of bleeding or when there may be increased risk of perioperative bleeding.

Warfarin or antiplatelet agents such as clopidogrel (Plavix®), ticlopidine (Ticlid®), prasugrel (Effient®), ticagrelor (Brilinta®) and/or aspirin are commonly used in patients who have experienced a DVT or PE, patients who have had an MI and/or who have undergone cardiac stent placement, or in patients with NVAF.⁷ As reviewed in the following sections, there is general agreement based on strong evidence that treatment regimens with these older anticoagulants/antiplatelet agents should not be altered before dental procedures.^{8, 14-16, 22, 25, 33-43}

Warfarin

A 2009 systematic review and meta-analysis found no increased risk of bleeding associated with continuing regular doses of warfarin in comparison with discontinuing or modifying the dose for patients undergoing single and multiple tooth extraction.³³ In its most recent statement, the American Academy of Neurology recommended that patients taking aspirin or warfarin for stroke prevention and undergoing dental procedures continue taking their medications.³⁵

A 2015 systematic review of management of dental extractions in patients receiving warfarin determined that patients whose International Normalized Ratio (INR; a measure of warfarin's therapeutic index) was in therapeutic range (i.e., 3.0 or less) could continue their regular warfarin regimen prior to the procedure.⁴¹ Based on a literature review, a 2016 Clinical Practice Statement from the American Academy of Oral Medicine determined that moderately invasive oral surgery (defined as "uncomplicated tooth extraction") is safe with an INR of 3.5, with some experts stating that it is safe up to 4.0.¹⁷ A 2008 systematic review and meta-analysis by Oake et al.⁴⁴ found that although the risks of hemorrhage and thromboembolism are reduced at an INR range of 2 to 3, ratios moderately higher than this range appeared to be safe and more effective than subtherapeutic ratios.

Single or Dual Antiplatelet Therapy

The American Heart Association, the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions, the American College of Surgeons, and the American Dental Association published a consensus opinion about drug-eluting stents and antiplatelet therapy (e.g., aspirin, clopidogrel, ticlopidine).^{9, 10} The consensus opinion states that healthcare providers who perform invasive or surgical procedures (e.g., dentists) and are concerned about periprocedural and postprocedural bleeding should contact the patient’s cardiologist regarding the patient's antiplatelet regimen and discuss optimal patient management, before discontinuing the antiplatelet medications. Given the importance of antiplatelet medications post-stent implantation in minimizing the risk of stent thrombosis, the medications should not be discontinued prematurely.^{9, 10}

A 2020 systematic review and meta-analysis⁴⁵ evaluated the incidence of bleeding after minor oral surgery in patients on dual antiplatelet therapy (aspirin plus another antiplatelet agent) compared with single-agent therapy or no antiplatelet therapy and found clinically similar rates of bleeding across the three groups. When bleeding did occur, it was managed with local measures and no fatal events occurred. The authors concluded that dual antiplatelet therapy interruption prior to minor oral surgery was not advised.

A 2013 systematic review¹⁴ found no clinically significant increased risk of postoperative bleeding complications from invasive dental procedures in patients on either single or dual antiplatelet therapy.

Some patients who are taking single or multiple anticoagulant medications may have additional co-morbid medical conditions or may be receiving other treatments/medications that can increase the risk of prolonged bleeding after dental treatment, including liver impairment or alcoholism; kidney failure; thrombocytopenia, hemophilia, or other hematologic disorders; or may be currently receiving a course of cytotoxic medication (e.g., cancer chemotherapy). In these situations, dental practitioners may wish to consult the patient's physician to determine whether care can safely be delivered in a primary care office.^{38, 39} Any suggested modification to the medication regimen prior to dental surgery should be done in consultation with and on advice of the patient's physician.^{13, 17, 37, 46}

There is general agreement that in most cases, treatment regimens with older anticoagulants (e.g., warfarin) and antiplatelet agents (e.g., clopidogrel, ticlopidine, prasugrel, ticagrelor, and/or aspirin) should not be altered before dental procedures. The risks of stopping or reducing these medication regimens (i.e., thromboembolism, stroke, MI) far outweigh the consequences of prolonged bleeding, which can be controlled with local measures. In patients with comorbid medical conditions that can increase the risk of prolonged bleeding after dental treatment or who are receiving other therapy that can increase bleeding risk, dental practitioners may wish to consult the patient's physician to determine whether care can safely be delivered in a primary care office. Any suggested modification to the medication regimen prior to dental surgery should be done in consultation and on advice of the patient's physician.

On the basis of limited evidence, general consensus appears to be that in most patients who are receiving the newer direct-acting oral anticoagulants (i.e., dabigatran, rivaroxaban, apixaban, or edoxaban) and undergoing dental interventions (in conjunction with usual local measures to control bleeding), no change to the anticoagulant regimen is required. In patients deemed to be at higher risk of bleeding (e.g., patients with comorbid conditions or undergoing more extensive procedures associated with higher bleeding risk), consideration may be given, in consultation with and on advice of the patient's physician, to postponing the timing of the daily dose of the anticoagulant until after the procedure; timing the dental intervention as late as possible after last dose of anticoagulant; or temporarily interrupting drug therapy for 24 to 48 hours. Further research is needed to definitively establish periprocedural management strategies for these patients, especially those considered to be at higher risk of bleeding.

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