OBServaToIre National Des Patients AnTiphospholipidEs traités Par Anticoagulants Oraux Directs
OBServaToIre National Des Patients AnTiphospholipidEs traités Par Anticoagulants Oraux Directs
This registry will make it possible to collect large-scale data on SAPL patients, particularly those treated with DOACs, in order to better assess the frequency of thrombotic and hemorrhagic events in this population of "non-high-risk" thrombotic SAPL patients treated with DOACs. The results will help refine treatment recommendations and could form the basis of future clinical trials.
In this study, there will be no modification of the usual care and no additional follow-up. Follow-up will be carried out during the patient's usual visits in the context of his or her pathology, the frequency of which will be left to the discretion of the usual physician. No additional consultations/hospitalizations/examinations will be carried out as part of the study. Data normally recorded in the medical record will be collected over a 5-year period, in line with standard patient follow-up.
Direct oral anticoagulants (DOACs) are indicated as first-line therapy for the prevention of recurrence of venous thromboembolism. The management of APS patients is based on long-term anticoagulation, which the gold standard vitamin K antagonist (VKA) including warfarin. Managing VKA is sometimes a challenge in these patients due to their young age and prolonged treatment requiring regular monitoring of INR and numerous drug interactions. DOACs don't require biological monitoring so would represent a potential easier oral treatment for these APS patients.
In 2016, the first controlled randomized compared DOACs vs VKA in about fifty APS patients (RAPS study) using biological data (generation of thrombin). The safety profile (thrombotic recurrence / hemorrhage) seemed reassuring; However, the duration of follow-up and the number of included subjects were insufficient to conclude on clinical safety criteria.
Subsequently, case series have reported the use of DOACs in these patients. Thus, a meta-analysis on individual data covering all of the literature and including these case series was recently published: 447 APS patients treated with DOACs were included and for the first time, a rate of 16% recurrent thrombosis has been identified despite treatment. This recurrence rate is abnormally high compared to that with VKA. Some risk factors for recurrent thrombosis have been identified: the positivity of all antiphospholipid biological tests ("triple positivity"; OR = 4.3 [95% CI; 2.3-7.7]), and in patients treated with anti-Xa only (rivaroxaban or apixaban), a history of arterial thrombosis was associated with a higher risk of thrombotic recurrence (32% vs 14%, p = 0.006).
These results were confirmed by the TRAPS trial, which had to be prematurely stopped due to an excess of thrombotic events in the group of 59 "triple positive" APS patients treated with rivaroxaban (12% vs 0%) compared to the group treated with warfarin.
Thus, the use of DOACs does not appear to be risk free in all patients with APS, particularly those with "triple positivity" or those with a history of arterial thrombosis who represent a group of patients at "high risk" thrombosis.
The European Medicines Agency (EMA) has diffused a letter recommending against the use of DOACs in patients with APS, especially triple-positive patients, and the use of VKAs has to be considered. It is important to emphasize that this modification does not constitute a contraindication to the use of DOACs but a recommendation.
For the other "non-high risk" APS patients who constitute the majority of APS patients, we have not strong arguments to justify a routine DOACs-VKA switch. Commonly in these patients, DOACs treatment was started in the acute phase of a thrombotic episode, before the diagnosis of APS was made. According to international recommendations, to conclude for an APS, it is necessary to control the aPL laboratory tests twice at least 3 months apart to conclude that there is persistent positivity. Thus the diagnosis of APS is often made several months after the thrombotic event and therefore several months after the introduction of anticoagulant treatment.
Taking into account the advantages on the quality of life of DOACs compared to VKAs, patients are often not in favor of modifying their anticoagulant treatment, especially if it has been started for many years with good tolerance. In addition, the switch from one well-balanced anticoagulant treatment to another is not without risk in terms of thrombosis or bleeding. It is for these reasons that a number of patients with APS remain on DOACs.
On the other hand, the European League Against Rheumatism (EULAR) recommends - in its recommendations for the APS management published on May 15, 2019 - to contraindicate the use of rivaroxaban in "high risk" APS patients but does not position itself in relation to the use of other DOACs or in "non-high risk" patients. In these patients, treatment could be continued and their follow-up would then become crucial to confirm that "non-high risk" patients are indeed at low risk of recurrent thrombosis.
For these "non-high risk" patients currently treated with DOACs, we do not currently have follow-up data on a sufficient group of patients. Therefore, it becomes urgent to collect in an exhaustive and prospective manner, all the data of "non-high risk" APS patients treated with DOACs and until then not monitored. The results will make it possible to better identify the target population that could benefit from this type of treatment. The results would also help prevent unnecessary VKA relays that carry their own risks.
Inclusion Criteria:
Exclusion Criteria:
Incomplete Sydney classification criteria
Presence of a triple antiphospholipid positivity
History of arterial thrombosis
Persons referred to in Articles L. 1121-5, L. 1121-7 and L1121-8 of the French Public Health Code:
Persons deprived of their liberty by a judicial or administrative decision, persons undergoing psychiatric treatment under Articles L. 3212-1 and L. 3213-1 of the French Public Health Code.
Signature of the research participation opposition form