Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome
Open accessAbstract
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.
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A recent RCT of rivaroxaban versus warfarin in antiphospholipid syndrome patients with triple antiphospholipid antibody positivity was prematurely terminated because of an excess of thromboembolic events, mostly arterial, in the rivaroxaban arm.
“A recent RCT of rivaroxaban versus warfarin in patients with APS with triple aPL positivity was prematurely terminated due to an excess of thromboembolic events (mostly arterial) in the rivaroxaban arm.7”
From EULAR recommendations for the management of antiphospholipid syndrome in adults (2019) · cites this paper as [7]
The premature interruption of the TRAPS trial led the EMA to warn against the use of DOACs in APS patients, recommending the exclusion of APS in patients with acute thrombosis after unspecified causes for whom treatment with a DOAC is indicated, shifting anticoagulation to VKA if there is an anti-phospholipids-antibodies positivity.
“The premature interruption of the TRAPS trial [65] led the EMA (European Medicines Agency) to warn against the use of DOACs in APS patients, recommending the exclusion of APS in patients with acute thrombosis after unspecified causes for whom treatment with a DOAC is indicated, shifting anticoagulation to VKA if there is an anti-phospholipids-antibodies positivity [67].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [65]
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 [65]
A recent randomised, open-label trial comparing rivaroxaban to warfarin in APS with triple antiphospholipid positivity was prematurely terminated due to an excess of thromboembolic events in the rivaroxaban arm.
“A recent randomised, open-label trial comparing rivaroxaban to warfarin in APS with triple aPL positivity (~21% of patients had SLE-APS) was prematurely terminated due to an excess of thromboembolic events in the rivaroxaban arm.”
From 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus (2019) · cites this paper as [139]
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“The premature interruption of the TRAPS trial [65] led the EMA (European Medicines Agency) to warn against the use of DOACs in APS patients, recommending the exclusion of APS in patients with acute thrombosis after unspecified causes for whom treatment with a DOAC is indicated, shifting…”
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- Authors
- Pengo, V., Denas, G., Zoppellaro, G., Jose, S. P., Hoxha, A., Ruffatti, A., Andreoli, L., Tincani, A., Cenci, C., Prisco, D., Fierro, T., Gresele, P., Cafolla, A., De Micheli, V., Ghirarduzzi, A., Tosetto, A., Falanga, A., Martinelli, I., Testa, S., Barcellona, D., Gerosa, M., & Banzato, A.
- Affiliations
- Cardiology Clinic, Thrombosis Centre, Department of Cardiac Thoracic and Vascular Sciences, and
- University of Padua (IT)
- Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy;
- University of Florence (IT)
- University of Perugia (IT)
- Sapienza University of Rome (IT)
- Transfusion Medicine, District Hospital, Merate, Italy;
- Santa Maria Nuova Hospital (IT)
- Ospedale San Bortolo (IT)
- Ospedale Papa Giovanni XXIII (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Azienda Socio Sanitaria Territoriale di Cremona (IT)
- University of Cagliari (IT)
- University of Milan (IT)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2018-09-27
- Volume
- 132
- Issue
- 13
- Pages
- 1365-1371
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2813643485
- Cited by
- 822
- References
- 35
- Citations by year
- 2026: 66 · 2025: 64 · 2024: 103 · 2023: 113 · 2022: 110 · 2021: 112 · 2020: 143 · 2019: 90 · 2018: 18 · 2017: 1
- FWCI
- 77.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion, other-oa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Università degli Studi di Padova
- Università degli Studi di Firenze
- Università degli Studi di Brescia
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Keywords
- rivaroxaban, warfarin, antiphospholipid syndrome, thromboprophylaxis, triple positivity, lupus anticoagulant, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, thromboembolic events, major bleeding, ischemic stroke, myocardial infarction, non-inferiority
- MeSH terms
- Rivaroxaban, Adult, Anticoagulants, Female, Humans, Italy, Male, Middle Aged, Prospective Studies, Thromboembolism, Warfarin, Antiphospholipid Syndrome, Treatment Outcome, Factor Xa Inhibitors
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