The treatment of patients taking anticoagulant or antiplatelet medication raises safety concerns in terms of the potential risk of bleeding complications following invasive dental procedures. The anticoagulant warfarin, and antiplatelet agents aspirin and clopidogrel, have been widely used for many years and most dental practitioners will be familiar with well-established guidelines for the dental care of patients taking these drugs. However, in recent years several newer oral anticoagulants (NOACs1; Novel Oral Anticoagulants, also known as DOACs1 or TSOACs; namely apixaban, dabigatran and rivaroxaban) and antiplatelet drugs (prasugrel and ticagrelor) have become available in the UK. A lack of evidence in the context of dentistry to inform the treatment of patients taking these newer drugs has led to uncertainty around the appropriate management of these patients.
This guidance aims to clarify the current recommendations and expert advice for the newer oral anticoagulants and antiplatelet drugs and presents these, along with up-to-date recommendations for the more established medications, within a single widely available information resource.
1.1 Scope of the Guidance
While there are a number of existing guidelines for the treatment of dental patients taking warfarin2-4 or aspirin4,5, national dental clinical practice guidelines addressing the newer medications are lacking.6 This guidance aims to encourage a consistent approach to the management of dental treatment for patients who are taking anticoagulants or antiplatelet drugs by providing evidence, where available, and expert opinion based recommendations and information relevant to dental treatment, for the existing, new and emerging anticoagulants and antiplatelet drugs. Through the clinical practice advice provided, the guidance also aims to empower dental staff to treat this patient group within primary care thereby minimising the need for consultation and referral to secondary care. The clinical management of dental patients who are taking anticoagulants or antiplatelet drugs and being treated as inpatients within a medical hospital setting is beyond the scope of this guidance and is not discussed.
The guidance is primarily directed at dentists, hygienists and therapists in primary care dental practice, including the general dental service and public dental service, and will also be of relevance to the secondary care dental service, those involved in dental education and undergraduate trainees.
To develop the recommendations for this guidance, SDCEP convened a multidisciplinary guidance development group including medical and dental practitioners and specialists along with a patient representative (Appendix 1). The key recommendations presented in the guidance were developed through considered judgements, made by the group, based on the existing guidelines, the available evidence, clinical experience, expert opinion and patient and practitioner perspectives. Details of these considered judgements are available at www.sdcep.org.uk. The impact of potential barriers identified during guidance development and through stakeholder involvement and external consultation was also considered when formulating the recommendations.
This process for development of recommendations followed the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach (www.gradeworkinggroup.org). The strength of each key recommendation is stated directly after the recommendation with a brief justification in the accompanying text. A strong recommendation is one where it is considered, based on all the available information and weighing up the balance of benefits versus risk, that almost all individuals would choose this option. A conditional recommendation is one where there is a finer balance between the options and it is likely that the majority but not all would choose the recommended option. In the case of a conditional recommendation, the dental practitioner should expect to spend more time discussing the treatment management options so that the patient can make an informed decision. Further details can be found in Appendix 1 and at www.sdcep.org.uk.
Other clinical practice advice in this guidance is based on consensus, expert opinion and existing best practice as identified in the accompanying text. These advice points are indicated with bullet points.
1.3 Supporting Tools
Tools to support the implementation of the guidance are available for access and download from the SDCEP website (www.sdcep.org.uk) and include:
A quick reference guide with the recommendations provided as a treatment planning flow chart.
Patient information leaflets for each of the main drug groups, which can be printed for providing to patients, ideally prior to treatment.
Post-treatment patient advice sheets, which can be modified for use.
A template form for recording local contact details for medical, pharmacy, haematology, cardiology and secondary dental care support.
1.4 Statement of Intent
This guidance is based on careful consideration of the available information and resources at the time of issue and has been developed through consultation with experts and end-users (see Appendix 1). As guidance, it does not override the healthcare professional’s right, and duty, to make decisions appropriate to each patient, with their informed consent. However, it is advised that departures from this guidance, and the reasons for this, are fully documented in the patient’s clinical record.
SDCEP is funded by NES (NHS Education for Scotland). The views and opinions of NES have not in any way influenced the recommendations made in this guidance.
2 Anticoagulants and Antiplatelet Drugs
2.1 What are Anticoagulants and Antiplatelet Drugs?
Anticoagulants and antiplatelet drugs are agents that reduce the ability of blood to form clots, or coagulate. Blood clotting is a process triggered naturally in response to damage to blood vessels from injury or invasive procedures. Platelets within the blood become activated locally, resulting in an increased tendency to adhere to each other and to damaged blood vessel endothelium (primary haemostasis). At the same time a cascade of reactions is initiated converting inactive coagulation factors to their active forms, ultimately leading to the production of the protein fibrin, the activated cross-linking form of fibrinogen. Fibrin stabilises the primary platelet plug by cross-linking the platelets to each other and to the damaged blood vessel wall to prevent further blood loss (secondary haemostasis).
Anticoagulants and antiplatelet drugs exert their effects at different stages in the coagulation process. Antiplatelet drugs, including aspirin, dipyridamole and clopidogrel, interfere with platelet aggregation by reversibly or irreversibly inhibiting various steps in the platelet activation required for primary haemostasis. The various anticoagulant drugs inhibit the production or activity of the factors that are required for the coagulation cascade. For example, warfarin and the other vitamin K antagonists (VKAs; acenocoumarol and phenindione) work by inhibiting the vitamin K-dependent modification of prothrombin and other coagulation factors, which is required for their normal function, and in this way they impair secondary haemostasis.
Blood coagulation in response to injury is an essential process. However, certain medical conditions, including atherosclerosis and cardiac arrhythmias, can predispose individuals to the risk of a thrombosis, where a blood clot (thrombus) blocks a blood vessel, either at the site of formation or after travelling to another critical site (thromboembolism), with potentially catastrophic consequences such as heart attack, pulmonary embolism or stroke. Anticoagulants and antiplatelet drugs are prescribed to reduce the risk of such an event in patients with vascular, thromboembolic or cardiac conditions, a history of stroke or following surgical procedures such as heart valve replacements, cardiac stents and joint replacements. However, this reduction in risk of thromboembolic events comes at the cost of an increased risk of bleeding, either spontaneously or associated with invasive procedures. The balance of these risks for an individual patient is the primary consideration in the management of dental patients who are taking anticoagulants or antiplatelet drugs and require dental treatment.
The anticoagulants and antiplatelet drugs prescribed in the UK are listed in Appendix 2, and the conditions for which they are commonly prescribed are indicated in Appendix 3.
2.2 The New Anticoagulants and Antiplatelet Drugs
Warfarin has been in use for over 50 years and is still one of the most widely used medications for the treatment and prophylaxis of thromboembolism. However, it does have a number of limitations, including a narrow therapeutic range, sensitivity to diet and drug interactions and the requirement for frequent monitoring and dose adjustment.7 Since 2008, a group of newer oral anticoagulants has been available which overcome many of these limitations.8 Dabigatran (Pradaxa) is a direct inhibitor of the coagulation factor thrombin, while apixaban (Eliquis) and rivaroxaban (Xarelto) inhibit Factor Xa of the coagulation cascade. These drugs produce a more predictable level of anticoagulation than warfarin9 and so do not require monitoring, are easier to manage and are potentially more effective and safer. These drugs are now licensed for use in the UK for a number of indications (see Appendix 3) and consequently the number of patients who present for dental treatment while taking these drugs is increasing. Notably, the National Institute for Health and Care Excellence (NICE) now recommends the use of apixaban, rivaroxaban and dabigatran in preference to aspirin for stroke prevention in patients with atrial fibrillation.10
Two new generation antiplatelet drugs11, namely prasugrel (Efient) and ticagrelor (Brilique), have also become available in recent years, providing alternatives to clopidogrel. These are more potent antiplatelet agents with a more rapid onset of action, more predictable absorption and improved efficacy for some outcomes. Their use is currently limited to patients with acute coronary syndrome and coronary stents and each is usually prescribed in combination with aspirin, as a dual therapy.12,13
A number of other new anticoagulants and antiplatelet drugs are currently in development. The two which are closest to being available in the UK are the oral anticoagulant, edoxaban, and the antiplatelet drug, vorapaxar (current in July 2015). Edoxaban (Lixiana), a once a day factor Xa inhibitor like rivaroxaban, was granted EU marketing authorisation in June 2015. Vorapaxar (Zontivity) was granted EU marketing authorisation in January 2015. More information about these drugs will be available via the electronic Medicines Compendium website (www.medicines.org.uk) when they are marketed in the UK.