Direct Oral Anticoagulants Use in Antiphospholipid Syndrome: Are These Drugs an Effective and Safe Alternative to Warfarin? A Systematic Review of the Literature

Abstract

The recent RAPS trial demonstrated that APS patients treated with rivaroxaban had a significant twofold-increased thrombin potential, suggesting a higher thrombotic risk, in comparison with warfarin users. Furthermore, several reports of APS patients treated with DOACs have raised safety issues. Our systematic review identified 122 published APS patients treated with DOACs; among them, 19 experienced a recurrent thrombosis while on DOACs. Of note, triple positivity (positivity of all three laboratory criteria for APS) was associated with a 3.5-fold increased risk for recurrent thrombosis. In conclusion, DOACs should be used with caution in APS patients and randomized control trials with clinical primary endpoints assessing clinical efficacy and safety are awaited to establish whether the prescription of DOACs could be a safe alternative to warfarin.

Recurrent Thrombosis in Patients with Antiphospholipid Syndrome Receiving Newer Oral Anticoagulants: A Case Report and Review of Literature

“…Similarly, there are at least 28 other cases of failure of NOACs in preventing thrombotic events in APS reported in literature thus far, which have been summarized in Table 1. Dufrost et al 13 recently published a systematic literature review of 122 APS patients identified in the literature to have been treated with NOACs and found that 19 of them had recurrent thrombosis while on NOACs.…”

“…The RAPS study did not have sufficient numbers of patients in either arm to achieve enough power for definite clarification. 13 The investigators reported non-inferiority of rivaroxaban as compared to VKAs, as the ETP for rivaroxaban did not reach the non-inferiority level, which was set at < 20% difference from warfarin in mean percentage change. However, the peak thrombin generation for rivaroxaban was significantly higher at 93.8 nMol/L as compared to warfarin at 79.9 nMol/L.…”

“…The study also did not include enough high-risk patients as defined by triple antibody positivity, arterial thrombosis, and recurrent venous thrombosis. 13 However, there have been reports of success as well. Betancur et al 15 reviewed eight patients with no recurrences of thrombosis after a 19-month mean follow up.…”

The Role of Transcranial Doppler Monitoring in Patients with Multi‐Territory Acute Embolic Strokes: A Review

“…The most recent American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend antiplatelet therapy for cases with ischemic stroke or TIA and positive aPL that do not fulfill the criteria for APS, and an option for anticoagulation when criteria for APS are met . The off‐label use of direct oral anticoagulants (DOACs) is controversial . The only randomized phase III trial comparing rivaroxaban with warfarin in high‐risk APS patients with triple antibody positivity was terminated prematurely due to increased cerebrovascular events in the rivaroxaban group .…”

Antiphospholipid syndrome: an update for clinicians and scientists

“…Bleeding events and overall adverse events were also similar between the groups [14]**. While a full recounting of this important trial is beyond the scope of this brief review, we would refer you to a detailed comment on the topic [66]. Related to our discussion of the complement pathway, a post-hoc analysis of the RAPS trial revealed that, prior to randomization, APS patients had significantly higher markers of complement activation as compared with normal controls [19]*.…”