Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial
Abstract
Background The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain. Objective To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS. Design 3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36). Setting 6 university hospitals in Spain. Participants 190 adults (aged 18 to 75 years) with thrombotic APS. Intervention Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis). Measurements The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor bleeding. Results After 3 years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76]). Stroke occurred more commonly in patients receiving rivaroxaban (9 events) than in those receiving VKAs (0 events) (corrected RR, 19.00 [CI, 1.12 to 321.9]). Major bleeding occurred in 6 patients (6.3%)…
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Recent clinical trials of patients with APS randomized to receive VKA or rivaroxaban showed a significant excess of thrombosis recurrence in rivaroxaban patients.
“Recent clinical trials of patients with APS randomized to receive VKA or rivaroxaban (a direct factor Xa inhibitor) showed a significant excess of thrombosis recurrence in rivaroxaban patients [65,66].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [66]
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“Thus, to define the noninferiority margin, we considered meta-analysis data comparing warfarin with placebo with regard to stroke incidence in patients with atrial fibrillation (29), in whom the relative risk for stroke reduction was estimated as 0.”
MethodUpdate of the guidelines for lupus anticoagulant detection
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GAPSS: the Global Anti-Phospholipid Syndrome Score
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Kleindorfer, D. O., Towfighi, A., Chaturvedi, S., Cockroft, K. M., Gutierrez, J., Lombardi-Hill, D., Kamel, H., Kernan, W. N., Kittner, S. J., Leira, E. C., et al. (2021) · Stroke · doi:10.1161/str.0000000000000375 · Cited by 3,237 · see citing works
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Lupus Anticoagulant Detection under the Magnifying Glass
Molinari, A. C., Martini, T., Banov, L., Ierardi, A., Leotta, M., Strangio, A., & Santoro, R. C. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12206654 · Cited by 9 · see citing works
- Authors
- Ordi-Ros, J., Sáez-Comet, L., Pérez-Conesa, M., Vidal, X., Riera-Mestre, A., Castro-Salomó, A., Cuquet-Pedragosa, J., Ortiz-Santamaria, V., Mauri-Plana, M., Solé, C., & Cortés-Hernández, J.
- Affiliations
- Vall d'Hebrón Research Institute, Barcelona, Spain (J.O., X.V., C.S., J.C.)
- Miguel Servet Hospital, Zaragoza, Spain (L.S., M.P.)
- Hospital Universitario Miguel Servet (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Bellvitge University Hospital-IDIBELL, Barcelona, Spain (A.R.)
- Sant Joan de Reus University Hospital, Reus, Spain (A.C.)
- Hospital General de Granollers (ES)
- Granollers University Hospital, Granollers, Spain (J.C., V.O.)
- Hospital de Mataró (ES)
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2019-11-19
- Volume
- 171
- Issue
- 10
- Pages
- 685-694
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W2980869818
- Cited by
- 324
- References
- 8
- Citations by year
- 2026: 31 · 2025: 34 · 2024: 55 · 2023: 43 · 2022: 38 · 2021: 50 · 2020: 67 · 2019: 5 · 2018: 1
- FWCI
- 30.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- rivaroxaban, vitamin K antagonists, antiphospholipid syndrome, thrombotic antiphospholipid syndrome, direct oral anticoagulants, recurrent thrombosis, major bleeding, stroke, anticoagulation, non-inferiority, livedo racemosa, valvular heart disease, arterial thrombosis
- MeSH terms
- Rivaroxaban, Adult, Anticoagulants, Female, Hemorrhage, Humans, Male, Middle Aged, Recurrence, Thrombosis, Vitamin K, Warfarin, Antiphospholipid Syndrome, Stroke, Secondary Prevention, Factor Xa Inhibitors
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