Oral Anticoagulant and Antiplatelet Medications and Dental Procedures

Key Points

There is both a growing number of individuals prescribed anticoagulation or antiplatelet therapy, as well as medications for this purpose. There is strong evidence for the older medications (i.e., warfarin, antiplatelet agents), as well as limited evidence for the newer direct-acting oral anticoagulants medications that, for most patients, it is not necessary to alter anticoagulation or antiplatelet therapy prior to dental intervention.
Drug Class Drug Names
Anticoagulant*
  • warfarin (Coumadin®)
Antiplatelet agents*
  • clopidogrel (Plavix®)
  • ticlopidine (Ticlid®)
  • prasugrel (Effient®)
  • ticagrelor (Brilinta®)
  • aspirin
Direct-acting oral anticoagulants**
  • dabigatran (Pradaxa®)
  • rivaroxaban (Xarelto®)
  • apixaban (Eliquis®)
  • edoxaban (Savaysa® [Lixiana® in Europe, Japan, elsewhere])

* Strong evidence
** Limited evidence

Typical Patient

No need to discontinue medication; use local measures to control bleeding

Patients with Higher Risk of Bleeding

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


Introduction

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.

Evidence: Direct-Acting Oral Anticoagulants

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 Association27, 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 201513, 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.

Evidence: Warfarin and Antiplatelet Agents

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.

Other Patient Considerations

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

Summary

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.

References
  1. Boehringer Ingelheim Pharmaceuticals Inc. Pradaxa® (dabigatran etexilate mesylate) capsules for oral use (rev. 7/2020). Accessed August 31, 2020.
  2. Bristol-Myers Squibb. Eliquis® (apixaban) tablets, for oral use (rev. 11/2019). Accessed August 31, 2020.
  3. Daiichi Sankyo Inc. Savaysa (edoxaban) tablets for oral use (rev. 04/2020). Accessed August 31, 2020.
  4. Janssen Pharmaceuticals Inc. Xarelto® (rivaroxaban) tablets for oral use (rev. 03/2020). Accessed August 31, 2020.
  5. Which oral anticoagulant for atrial fibrillation. Med Lett Drugs Ther 2016;58(1492):45-6.
  6. Which oral anticoagulant for atrial fibrillation? JAMA 2016;315(19):2117-8.
  7. Gurbel PA, Myat A, Kubica J, Tantry US. State of the art: Oral antiplatelet therapy. JRSM Cardiovasc Dis 2016;5:2048004016652514.
  8. Napenas JJ, Hong CH, Brennan MT, et al. The frequency of bleeding complications after invasive dental treatment in patients receiving single and dual antiplatelet therapy. J Am Dent Assoc 2009;140(6):690-5.
  9. Grines CL, Bonow RO, Casey DE, Jr., et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. J Am Dent Assoc 2007;138(5):652-5.
  10. Grines CL, Bonow RO, Casey DE, Jr., et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation 2007;115(6):813-8.
  11. Teoh L, Moses G, McCullough MJ. A review of drugs that contribute to bleeding risk in general dental practice. Aust Dent J 2020;65(2):118-30.
  12. Wahl MJ. The mythology of anticoagulation therapy interruption for dental surgery. J Am Dent Assoc 2018;149(1):e1-e10.
  13. Thean D, Alberghini M. Anticoagulant therapy and its impact on dental patients: a review. Aust Dent J 2016;61(2):149-56.
  14. Napenas JJ, Oost FC, DeGroot A, et al. Review of postoperative bleeding risk in dental patients on antiplatelet therapy. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115(4):491-9.
  15. Jeske AH, Suchko GD. Lack of a scientific basis for routine discontinuation of oral anticoagulation therapy before dental treatment. J Am Dent Assoc 2003;134(11):1492-7.
  16. Aframian DJ, Lalla RV, Peterson DE. Management of dental patients taking common hemostasis-altering medications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103 Suppl:S45 e1-11.
  17. AAOM Clinical Practice Statement: Subject: Management of Patients on Warfarin Therapy. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122(6):702-04.
  18. Kaplovitch E, Dounaevskaia V. Treatment in the dental practice of the patient receiving anticoagulation therapy. J Am Dent Assoc 2019;150(7):602-08.
  19. Ockerman A, Miclotte I, Vanhaverbeke M, et al. Local haemostatic measures after tooth removal in patients on antithrombotic therapy: a systematic review. Clin Oral Investig 2019;23(4):1695-708.
  20. Owattanapanich D, Ungprasert P, Owattanapanich W. Efficacy of local tranexamic acid treatment for prevention of bleeding after dental procedures: A systematic review and meta-analysis. J Dent Sci 2019;14(1):21-26.
  21. Daniels PR. Peri-procedural management of patients taking oral anticoagulants. BMJ 2015;351:h2391.
  22. Chahine J, Khoudary MN, Nasr S. Anticoagulation Use prior to Common Dental Procedures: A Systematic Review. Cardiol Res Pract 2019;2019:9308631.
  23. Johnston S. An evidence summary of the management of patients taking direct oral anticoagulants (DOACs) undergoing dental surgery. Int J Oral Maxillofac Surg 2016;45(5):618-30.
  24. Lanau N, Mareque J, Giner L, Zabalza M. Direct oral anticoagulants and its implications in dentistry. A review of literature. J Clin Exp Dent 2017;9(11):e1346-e54.
  25. Miller CS. A perspective on "The mythology of anticoagulation interruption for dental surgery". J Am Dent Assoc 2018;149(1):3-6.
  26. Mauprivez C, Khonsari RH, Razouk O, et al. Management of dental extraction in patients undergoing anticoagulant oral direct treatment: a pilot study. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122(5):e146-e55.
  27. Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17(10):1467-507.
  28. Heidbuchel H, Verhamme P, Alings M, et al. Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: Executive summary. Eur Heart J 2017;38(27):2137-49.
  29. Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15(5):625-51.
  30. Manfredi M, Dave B, Percudani D, et al. World workshop on oral medicine VII: Direct anticoagulant agents management for invasive oral procedures: A systematic review and meta-analysis. Oral Dis 2019;25 Suppl 1:157-73.
  31. Lusk KA, Snoga JL, Benitez RM, Sarbacker GB. Management of Direct-Acting Oral Anticoagulants Surrounding Dental Procedures With Low-to-Moderate Risk of Bleeding. J Pharm Pract 2018;31(2):202-07.
  32. Elad S, Marshall J, Meyerowitz C, Connolly G. Novel anticoagulants: general overview and practical considerations for dental practitioners. Oral Dis 2016;22(1):23-32.
  33. Nematullah A, Alabousi A, Blanas N, Douketis JD, Sutherland SE. Dental surgery for patients on anticoagulant therapy with warfarin: a systematic review and meta-analysis. J Can Dent Assoc 2009;75(1):41.
  34. Douketis JD, Berger PB, Dunn AS, et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(6 Suppl):299S-339S.
  35. Armstrong MJ, Gronseth G, Anderson DC, et al. Summary of evidence-based guideline: periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2013;80(22):2065-9.
  36. van Diermen DE, Aartman IH, Baart JA, Hoogstraten J, van der Waal I. Dental management of patients using antithrombotic drugs: critical appraisal of existing guidelines. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107(5):616-24.
  37. van Diermen DE, van der Waal I, Hoogstraten J. Management recommendations for invasive dental treatment in patients using oral antithrombotic medication, including novel oral anticoagulants. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116(6):709-16.
  38. Perry DJ, Noakes TJ, Helliwell PS, British Dental Society. Guidelines for the management of patients on oral anticoagulants requiring dental surgery. Br Dent J 2007;203(7):389-93.
  39. United Kingdom National Health Service. Surgical management of the primary care dental patient on antiplatelet medication. National Electronic Library of Medicines:  2007. Accessed August 31, 2020.
  40. Alaali Y, Barnes GD, Froehlich JB, Kaatz S. Management of oral anticoagulation in patients undergoing minor dental procedures. J Mich Dent Assoc 2012;94(8):36-41.
  41. Weltman NJ, Al-Attar Y, Cheung J, et al. Management of dental extractions in patients taking warfarin as anticoagulant treatment: A systematic review. J Can Dent Assoc 2015;81:f20.
  42. Dunn AS, Turpie AG. Perioperative management of patients receiving oral anticoagulants: a systematic review. Arch Intern Med 2003;163(8):901-8.
  43. Madrid C, Sanz M. What influence do anticoagulants have on oral implant therapy? A systematic review. Clin Oral Implants Res 2009;20 Suppl 4:96-106.
  44. Oake N, Jennings A, Forster AJ, et al. Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a systematic review and meta-analysis. Cmaj 2008;179(3):235-44.
  45. Ockerman A, Bornstein MM, Leung YY, et al. Incidence of bleeding after minor oral surgery in patients on dual antiplatelet therapy: a systematic review and meta-analysis. Int J Oral Maxillofac Surg 2020;49(1):90-98.
  46. Hupp WS. Cardiovascular Diseases. In: Patton LL, Glick M, editors. The ADA Practical Guide to Patients with Medical Conditions. 2nd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2016. p. 25-42.




ADA Resources
JADA for articles on anticoagulants and dental procedures

ADA Library Services

ADA Catalog:  The ADA Practical Guide to Patients with Medical Conditions



Other Resources
U.S. Food & Drug Administration MedWatch Program. If a practitioner suspects a patient to have had an adverse drug reaction, they may contact the FDA’s MedWatch program online or by calling 800-FDA-1088.