Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome

Abstract

Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272.

New guidelines from the Thrombosis and Haemostasis Society of Australia and New Zealand for the diagnosis and management of venous thromboembolism

“…Direct oral anticoagulants (DOACs) and warfarin are equally effective and can be prescribed to most patients. GRADE: Strong; Evidence: High . DOACs do not require routine monitoring, have no known food interactions and few drug interactions, and are favoured in most instances.…”

Update on diagnosis and anticoagulant therapy for venous thromboembolism

“…In Australia, this means that apixaban or rivaroxaban will be considered over warfarin. 25 A recent study compared rivaroxaban versus LMWH in this patient group and reported that the rate of recurrent VTE after 6 months of treatment was 4% and 11% in the rivaroxaban and LMWH groups, respectively (hazard ratio 0.43; 95% confidence interval 0.19-0.99). 25 Cancer-associated VTE Patients with malignancy have a higher risk of VTE and treatment can often be difficult given the increased propensity for bleeding.…”

“…25 Cancer-associated VTE Patients with malignancy have a higher risk of VTE and treatment can often be difficult given the increased propensity for bleeding. In Australia, this means that apixaban or rivaroxaban will be considered over warfarin.…”

Oral anticoagulant monitoring: Are we on the right track?

“…Thus, dabigatran was compared to warfarin in a prospective study of patients with mechanical heart valves but the trial had to be terminated early due to both excess TE and bleeding with dabigatran . Likewise, a recent trial comparing rivaroxaban to warfarin in patients with high‐risk antiphospholipid antibody syndrome had to be discontinued early due to increased risk of TE and major bleeding in patients taking rivaroxaban . Based on these small but compelling trials, warfarin is the preferred oral anticoagulant in these high‐risk thrombogenic conditions.…”