Direct acting oral anticoagulants (DOACs) should not be used in patients with antiphospholipid syndrome (APS) due to a high risk of thrombotic events, the Therapeutic Goods Administration (TGA) has advised.
In a new safety advisory statement the regulator says apixaban (Eliquis), dabigatran etexilate (Pradaxa) and rivaroxaban (Xarelto) are not recommended in patients with APS, particularly high-risk patients who are triple positive for lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I antibodies.
The recommendation is based on results from the TRAPS1 study, which has shown an increase in the risk of recurrent thrombotic events with rivaroxaban compared to warfarin in patients with APS, a history of thrombosis and a high risk of recurrent thrombotic events (patients who are triple positive).
The TGA said the Product Information (PI) documents for the three DOACS is being updated to reflect the current state of evidence.
“While there are currently no completed controlled trials relating to this issue for the other two DOACs marketed in Australia, these medicines may be associated with a similar risk,” it said.
It also noted that final results were not yet available from an another randomised controlled trial comparing apixaban and warfarin for secondary prevention of thromboembolism in patients with APS (ASTRO-APS), which recently closed due to lack of enrolment.
A recent European Medicines Agency (EMA) review found that the use of DOACs in patients with APS could be associated with increased rates of recurrent thrombotic events compared with treatment with a vitamin K antagonist.
“The level of evidence for increased risk of recurrent thrombotic events in patients differs between agents, but there is insufficient evidence that any DOAC offers sufficient protection in patients with APS, particularly high risk patients, such as those who are triple positive for lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I antibodies,” the TGA concluded.
The TGA’s advice to clinicians is: “Identify patients you may have that are diagnosed with APS and are receiving treatment with a DOAC. Review whether continued treatment is appropriate, particularly in high-risk patients. If appropriate, consider changing to alternative therapy.”
A similar recommendation has been made by UK regulators.
A recent Australian review article on the management of patients with APS recommended anticoagulation with unfractionated heparin or low molecular weight heparin followed by a vitamin K antagonist (warfarin) for patients who developed unprovoked venous thrombosis.
For DOACs, the review noted the results from the TRAPS1 study but said there was “insufficient evidence to make recommendations on the use of direct oral anticoagulants in APS.”