Table 3.
International guideline recommendations/consensus suggestions on the use of DOACs in APS patients.
| Guidelines | Recommendations | Level of evidence |
|---|---|---|
| International guidelines on deep vein thrombosis/pulmonary embolism | ||
| ESC 2019 (42) | Indefinite treatment with a VKA is recommended for patients with APS | Ib* |
| DOACs are not recommended in patients with severe renal impairment, during pregnancy and lactation, and in patients with APS | IIIc* | |
| ASH 2020 (43) | For patients with DVT and/or PE, the ASH guideline panel suggests using DOACs over VKAs (conditional recommendation based on moderate certainty in the evidence of effects). Remarks: This recommendation may not apply to certain subgroups of patients, such as those with renal insufficiency (creatinine clearance, 30 mL/min), moderate to severe liver disease, or APS | Remark. Evidence not provided |
| NICE 2020 (44) | Offer people with confirmed proximal deep vein thrombosis or pulmonary embolism and an established diagnosis of triple positive APS LMWH concurrently with a VKA for at least 5 days, or until the INR is at least 2.0 in two consecutive readings, followed by a VKA on its own | ∧ |
| International guidelines on antiphospholipid syndrome | ||
| BSH Guidelines 2020 (45) |
Patients with arterial thrombosis For anticoagulation for treatment and secondary prophylaxis of arterial thrombosis in patients with APS, we recommend VKAs and do not recommend DOACs |
IB# |
|
Patients with triple positive APS and venous thrombosis We recommend against the initiation of DOACs for treatment or secondary prophylaxis in patients with venous thrombosis and known triple positive APS. For patients with triple positive APS who are currently on a DOAC, we recommend switching from the DOAC to a VKA after discussion with patients regarding the available evidence. For those patients who do not wish to switch, we recommend continuation of the DOAC over no anticoagulation |
IB# | |
|
Patients with non-triple positive APS and venous thrombosis There is insufficient evidence to make strong recommendations in this group of patients. We suggest against the initiation of DOACs for treatment or secondary prophylaxis in patients with venous thrombosis and known non-triple positive APS. Patients who are already on a DOAC may continue or switch to a VKA after discussion with the patient taking into account their clinical history, treatment adherence and previous experience. For those patients who do not wish to switch, we recommend continuation of the DOAC over no anticoagulation |
IIC# | |
| ISTH 2020 guidance (46) |
We recommend that for the treatment of thrombotic APS among patients with any of the following (termed “high-risk” APS patients) (a) triple positivity, (b) arterial thrombosis, (c) small vessel thrombosis or organ involvement (d) heart valve disease according to Sydney criteria, VKA should be used instead of DOACs |
Not provided |
| We recommend that DOACs should not be used in APS patients with recurrent thrombosis while on therapeutic intensity VKA. In this circumstance, other therapeutic options may include an increased target INR range, treatment dose LMWH, or the addition of antiplatelet therapy | Not provided | |
| We recommend that DOACs should not be used in APS patients who are non-adherent to VKA. In this circumstance, other options may include education on adherence to VKA treatment along with frequent INR testing | Not provided | |
| In single or double positive non- “high risk” APS patients who have been on DOACs with good adherence for several months for a first episode of VTE, we recommend a discussion with the patient of options including perceived risks and uncertainties, in the spirit of shared decision-making and review of whether continued treatment with a DOAC is appropriate | Not provided | |
| In single- or double-positive non- “high-risk” APS patients with a single prior VTE requiring standard-intensity VKA, with allergy or intolerance to VKA or erratic INRs despite patient adherence, we suggest that alternative VKAs, if available, should be considered prior to consideration of a DOAC | Not provided | |
| EULAR 2019 (47) | In patients with definite APS and first venous thrombosis: Rivaroxaban should not be used in patients with triple aPL positivity due to the high risk of recurrent events | 1b/B§ |
|
In patients with definite APS and first venous thrombosis: DOACs could be considered in patients not able to achieve a target INR despite good adherence to VKA or those with contraindications to VKA (e.g., allergy or intolerance to VKA) |
5/D§ | |
|
In patients with definite APS and first arterial thrombosis: Rivaroxaban should not be used in patients with triple aPL positivity and arterial events |
Ib/B§ | |
|
In patients with definite APS and first arterial thrombosis: Based on the current evidence, we do not recommend use of DOACs in patients with definite APS and arterial events due to the high risk of recurrent thrombosis |
5/D§ | |
APS, antiphospholipid antibody syndrome; ASH, American Society of Hematology; BSH, British Society for Haematology; DOAC, direct oral anticoagulant; DVT, deep vein thrombosis; ESC, European Society of Cardiology; EULAR, European League Against Rheumatism; INR, international normalized ratio; ISTH, International Society on Thrombosis and Haemostasis; LMWH, low-molecular weight heparin; NICE, National Institute for Health and Care Excellence; PE, pulmonary embolism; VKA, vitamin K antagonist; VTE, venous thromboembolism.
*
ESC Committee for Practice Guidelines (CPG) policy.
§
Oxford Centre for Evidence-Based Medicine standards.
#
Grading of Recommendations Assessment, Development and Evaluation (GRADE).
∧
Based on the Medicines and Healthcare products Regulatory Agency alert and the experience and opinion of the Guideline Committee.