Which anticoagulant to use?
The THANZ recommend rivaroxaban or apixaban (both NOACs) in preference to warfarin for the treatment of VTE as there is no requirement for parenteral anticoagulation at initiation.1 Unlike warfarin, these agents require no dose adjustment (after the initial loading phase) or monitoring and are associated with fewer drug interactions and almost no food interactions. The direct antithrombin agent dabigatran requires an initial five-day period of heparin treatment and is not available on the PBS for treatment of VTE.
There are instances, however, in which rivaroxaban and apixaban should be avoided (Flowchart 3 and Table 2). NOACs are eliminated in part by the kidneys, and warfarin is preferred in advanced renal failure. There are limited high-quality data to support NOAC use in patients with weights of 120 kg or more, and these agents should be used with caution in this setting. Metabolism of NOACs is primarily hepatic and they should be avoided in patients receiving strong inhibitors of cytochrome P450 3A4, such as azole antimycotics and protease inhibitors for HIV. Women with childbearing potential should be made aware that NOACs have not been shown to be safe in pregnancy and breastfeeding. Contraceptive measures should be taken in sexually active women who are taking a NOAC, and before conception the NOAC should be replaced with a low molecular weight heparin (LMWH).8 An LMWH should be continued throughout the pregnancy and for the duration of breastfeeding.
There are limited data to guide the use of NOACs in antiphospholipid syndrome (APS), and warfarin is preferred in patients with this condition.16 APS is a rare condition; however, further laboratory testing should be considered before starting a NOAC in a patient with an otherwise unexplained prolonged activated partial thromboplastin time or a history of unprovoked thromboembolism or recurrent miscarriages. Data in patients with active malignancy are still evolving. Studies have suggested that rivaroxaban and apixaban are effective, but may be associated with increased rates of bleeding, especially in patients with mucosal disease.17,18 Nonetheless, due to their convenience, NOACs are increasingly employed in the treatment of cancer-associated VTE. Common anticoagulation regimens and their indications are outlined in Table 3.
Duration of anticoagulation
The optimal duration of anticoagulation for a patient with VTE is determined by the risk of clot progression or recurrence, which must be weighed against the risk of major bleeding (discussed above in ‘When to treat’) in patients who receive long-term anticoagulation (Table 2). Predicting which patients are at risk of further thrombotic events on withdrawal of anticoagulation remains challenging. Two questions are helpful:
- Does the patient have an indication for extended therapeutic anticoagulation?
- Does the patient have an indication for ongoing secondary prevention of VTE?
Patients who have experienced two or more unprovoked thromboses or have a diagnosis of antiphospholipid syndrome or active malignancy generally require indefinite anticoagulation. Secondary prevention of VTE should be considered in patients with a single unprovoked or nonsurgically provoked episode of VTE. There is equipoise in this group of patients, and personal preference should be considered. These patients can receive long-term prophylactic anticoagulation, with low-dose apixaban (2.5 mg twice daily) or rivaroxaban (10 mg daily) after an initial six to 12-month period of therapeutic anticoagulation.15,19 If NOACs are contraindicated, warfarin can be considered. Finally, cessation of anticoagulation after three to six months is appropriate if the patient is accepting of the 30% recurrence rate at five years.8
If the answers to the above questions are ‘no’, anticoagulation can usually be safely stopped after three to six months, or six to 12 weeks in the case of isolated distal DVT (Flowchart 4).8,10