Rivaroxaban does not show noninferiority to vitamin K antagonists in antiphospholipid syndrome
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Rivaroxaban failed to demonstrate noninferiority to dose-adjusted vitamin K antagonists in patients with thrombotic antiphospholipid syndrome, and the agent even showed a nonsignificant doubling of the risk for recurrent thrombosis, according to results from an open-label, randomized, noninferiority trial published in the Annals of Internal Medicine.
“So far, several case reports, case series, cross-sectional studies, and randomized controlled trials have provided conicting data on the efcacy of rivaroxaban in [antiphospholipid syndrome],” Josep Ordi-Ros, MD, PhD, of the department of internal medicine and the Rheumatology Research Group at Vall d’Hebro´n University Hospital Research Institute in Barcelona, Spain, and colleagues wrote.
Researchers conducted the 3-year trial at six university hospitals in Spain. A total of 190 patients were randomly assigned in a 1:1 ratio to receive 20 mg or 15 mg rivaroxaban per day — depending on renal function — or a dose-adjusted vitamin K antagonist (VKA).
After 3 years, recurrent thrombosis — the primary efficacy outcome — occurred in 11.6% of patients in the rivaroxaban group and 6.3% of patients in the VKA group (RR in the rivaroxaban group = 1.83; 95% CI, 0.71-4.76), exceeding the noninferiority margin.
According to the researchers, stroke was more common in patients who received rivaroxaban (nine events) compared with those who received VKAs (zero events; corrected RR = 19; 95% CI, 1.12-321.9).
During follow-up, major bleeding occurred in 6.3% of patients in the rivaroxaban group and 7.4% of the VKA group (RR = 0.86; 95% CI, 0.3-2.46).
Post-hoc analyses suggested that compared with patients treated with VKAs, those treated with rivaroxaban who had previous arterial thrombosis, livedo racemosa or an antiphospholipid syndrome-related cardiac valvular disease had an increased risk for recurrent thrombosis.
In an accompanying editorial, Denis Wahl, MD, PhD, and Virginie Dufrost, MD, both from the University of Lorraine in France, explained that the findings from this and previous studies suggest that direct oral anticoagulants should not be used in patients with high-risk antiphospholipid syndrome.
“Future research is needed to determine whether there is a lower-risk subset of patients with [antiphospholipid syndrome] who might be eligible for [direct oral anticoagulant] therapy,” they wrote. – by Erin Michael
Disclosures: Ordi-Ros reports institutional support from Bayer Hispania to conduct the study. Please see study for all other authors’ relevant financial disclosures. Wahl and Dufrost report no relevant financial disclosures.
Perspective
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Jori E. May, MD
This study provides further evidence of the risks associated with the use of rivaroxaban in antiphospholipid syndrome, primarily the increased risk for arterial thrombosis, compared with VKAs.
The previous TRAPS study illustrated this increased arterial thrombotic risk in patients with high-risk, “triple positive” antiphospholipid syndrome. The current study includes all patients meeting antiphospholipid syndrome diagnostic criteria, and a subgroup analysis did not find an associate between high-risk features and recurrent thrombosis, suggesting that even patients without known risk features may be subject to increased thrombotic risk with rivaroxaban.
Given the potential for the devastating clinical consequences of arterial thrombosis and a current inability to predict which patients are at highest risk, the use of rivaroxaban in antiphospholipid syndrome should be approached with extreme caution.
Reference:
Pengo V, et al. Blood. 2018;doi:10.1182/blood-2018-04-848333.
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