Can a patient with positive anti-phospholipid antibodies take a Direct Oral Anticoagulant (DOAC) rather than warfarin (coumarin)?

From the Guidelines

Patients with anti-phospholipid antibodies should not take a Direct Oral Anticoagulant (DOAC) and instead should be treated with warfarin. This recommendation is based on the latest evidence from the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack, which suggests that DOACs, such as rivaroxaban, are associated with a higher risk of thrombotic events in patients with antiphospholipid syndrome 1. The guideline specifically states that until other ongoing trials clarify whether the increased risk of thrombosis with DOACs is a class effect versus an individual drug effect, the use of DOACs is not recommended for antiphospholipid syndrome.

Some key points to consider when treating patients with anti-phospholipid antibodies include:

• The risk of recurrent thrombosis is high in patients with antiphospholipid syndrome who receive DOACs, as observed in observational data 1
• Warfarin appears to manage the complex hypercoagulable state in antiphospholipid syndrome more effectively than DOACs, with a recommended target INR of 2-3 for most patients
• The mechanism behind the difference in thrombotic events between warfarin and DOACs may relate to the complex hypercoagulable state in antiphospholipid syndrome, which warfarin appears to manage more effectively 1

It is essential to prioritize the patient's morbidity, mortality, and quality of life when making treatment decisions, and in this case, the evidence suggests that warfarin is the preferred treatment option over DOACs for patients with anti-phospholipid antibodies.

From the FDA Drug Label

5.6 Increased Risk of Thrombosis in Patients with Triple Positive Antiphospholipid Syndrome Direct-acting oral anticoagulants (DOACs), including Apixaban Tablets, are not recommended for use in patients with triple-positive antiphospholipid syndrome (APS) For patients with APS (especially those who are triple positive [positive for lupus anticoagulant, anticardioplipin, and anti-beta 2-glycoprotein I antibodies]), treatment with DOACs has been associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy

Patients with anti-phospholipid antibodies positive should not take a DOAC, such as apixaban, instead of warfarin due to the increased risk of thrombosis.

• The FDA drug label for apixaban 2 and rivaroxaban 3 explicitly states that DOACs are not recommended for patients with triple-positive antiphospholipid syndrome.
• This is because treatment with DOACs has been associated with increased rates of recurrent thrombotic events compared with vitamin K antagonist therapy.

From the Research

Antiphospholipid Antibodies and Anticoagulation Therapy

• Patients with antiphospholipid antibodies positive can be considered for direct oral anticoagulants (DOACs) rather than warfarin in certain situations, but the decision should be made cautiously 4, 5, 6, 7, 8.

Comparison of DOACs and Warfarin

• A study comparing rivaroxaban with warfarin in patients with single or double antibody-positive antiphospholipid syndrome found that the proportion of patients with a recurrent thromboembolism was almost three times higher in the DOAC group, although this was not statistically significant 4.
• Another study suggested that rivaroxaban may pose an increased risk for recurrent thromboembolism in low-risk APS patients that are single or double-antibody positive compared to warfarin 4.
• However, a retrospective study comparing the risk of recurrent thrombosis among single-positive APLS patients treated with DOACs (apixaban or rivaroxaban) and those treated with warfarin found no difference in event-free survival between groups 8.

Guidelines and Recommendations

• The European Society of Cardiology (ESC) and American Society of Hematology (ASH) guidelines recommend against the use of DOACs in all APS patients 6.
• The European League Against Rheumatism (EULAR), British Society for Haematology (BSH), and International Society on Thrombosis and Haemostasis (ISTH) guidance suggest that warfarin should be the first-choice treatment, but DOACs may be considered in patients with low-quality anticoagulation by warfarin or contraindications to warfarin 6.
• Patients with arterial APS or triple positivity should be treated with warfarin, while venous APS with single or double positivity may be candidates for DOACs, but high-quality studies are needed 6, 7.