Overview of oral anticoagulants

Oral anticoagulants available in Australia at the time of writing are listed in Oral anticoagulant drugs. Under most circumstances, oral anticoagulant therapy is preferred to parenteral therapy.

Direct-acting oral anticoagulants (DOACs) are also known as non–vitamin K antagonist oral anticoagulants (NOACs). DOACs (eg apixaban, rivaroxaban, dabigatran) are widely used in Australia for stroke prevention in patients with atrial fibrillation and for treatment and prophylaxis of venous thromboembolism (VTE) (ie deep vein thrombosis [DVT] or pulmonary embolism [PE]). Warfarin is the oral anticoagulant of choice for patients with rheumatic mitral stenosis and/or a mechanical heart valve, severe kidney impairment, and indications for which DOACs are not approved (eg treatment of arterial thromboembolism).

For patients with active cancer who require VTE prophylaxis or treatment, consider apixaban or rivaroxaban; data on the use of dabigatran for patients with VTE and active cancer are lacking. See VTE prophylaxis for patients with active cancer or VTE treatment for patients with active cancer for more information.

Request a serum beta human chorionic gonadotrophin (hCG) test for patients of childbearing age before starting any oral anticoagulant. At the time of writing, DOACs are contraindicated in pregnancy and breastfeeding because of limited safety data. Warfarin can be used safely while breastfeeding and a specialist may consider the use of warfarin during the second trimester of pregnancy.

DOAC dosing depends on the indication. Follow the dosage recommendation exactly; underdosing increases the risk of thrombus formation (eg underdosing in a patient with atrial fibrillation increases the risk of stroke), and overdosing can increase the bleeding risk. DOACs do not need anticoagulation monitoring. Warfarin dosing is individualised to ensure adequate anticoagulation, with the dose adjusted to achieve a target international normalised ratio (INR). Point-of-care devices allow suitable patients taking warfarin therapy to self-monitor INR.

DOACs have short half-lives—missed doses can result in a rapid loss of anticoagulant effect. Warfarin has a slower offset of anticoagulant effect following a missed dose.

Apixaban and rivaroxaban achieve maximum anticoagulant effect within 3 hours of the first dose so concurrent parenteral anticoagulation is not required when starting therapy (except for dabigatran for the treatment of venous thromboembolism¹). Warfarin takes several days to achieve therapeutic anticoagulation and causes an initial increase in prothrombotic potential. Consequently, when immediate anticoagulant effect is required (eg treatment of acute venous thromboembolism) warfarin must be started with concurrent parenteral anticoagulant therapy. When immediate anticoagulant effect is not required (eg stroke prevention for patients with permanent atrial fibrillation), start warfarin without concurrent parenteral therapy.

When an oral anticoagulant is started or the dose is modified during admission to hospital, liaise with the patient’s general practitioner (GP) on discharge to ensure continuation of appropriate laboratory and clinical monitoring. Poor communication between primary and secondary care is a common cause of unnecessary harm to patients.

Advice on how to change between DOACs and other anticoagulants is available from the New South Wales Clinical Excellence Commission. The Commission also provides information on DOAC drug interactions; see the NSW Clinical Excellence Commission website. While DOACs have fewer drug interactions than warfarin, drugs that affect the CYP3A4 and P-glycoprotein enzymes can have clinically significant interactions with DOACs.

The bleeding risk for oral anticoagulant therapy is determined by patient-specific factors or factors that affect anticoagulant exposure, such as the adequacy of warfarin monitoring or the anticoagulant pharmacokinetics; weigh the harm–benefit balance for oral anticoagulants for each patient.

Anticoagulation reversal agents are available for warfarin and dabigatran. Seek specialist haematologist advice on the use of andexanet alfa for the reversal of apixaban and rivaroxaban.