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Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial - PubMed

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Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial

Hannah Cohen et al. Lancet Haematol. 2016 Sep.

Abstract

Background: Rivaroxaban is established for the treatment and secondary prevention of venous thromboembolism, but whether it is useful in patients with antiphospholipid syndrome is uncertain.

Methods: This randomised, controlled, open-label, phase 2/3, non-inferiority trial, done in two UK hospitals, included patients with antiphospholipid syndrome who were taking warfarin for previous venous thromboembolism, with a target international normalised ratio of 2·5. Patients were randomly assigned 1:1 to continue with warfarin or receive 20 mg oral rivaroxaban daily. Randomisation was done centrally, stratified by centre and patient type (with vs without systemic lupus erythematosus). The primary outcome was percentage change in endogenous thrombin potential (ETP) from randomisation to day 42, with non-inferiority set at less than 20% difference from warfarin in mean percentage change. Analysis was by modified intention to treat. Other thrombin generation parameters, thrombosis, and bleeding were also assessed. Treatment effect was measured as the ratio of rivaroxaban to warfarin for thrombin generation. This trial is registered with the ISRCTN registry, number ISRCTN68222801.

Findings: Of 116 patients randomised between June 5, 2013, and Nov 11, 2014, 54 who received rivaroxaban and 56 who received warfarin were assessed. At day 42, ETP was higher in the rivaroxaban than in the warfarin group (geometric mean 1086 nmol/L per min, 95% CI 957-1233 vs 548, 484-621, treatment effect 2·0, 95% CI 1·7-2·4, p<0·0001). Peak thrombin generation was lower in the rivaroxaban group (56 nmol/L, 95% CI 47-66 vs 86 nmol/L, 72-102, treatment effect 0·6, 95% CI 0·5-0·8, p=0·0006). No thrombosis or major bleeding were seen. Serious adverse events occurred in four patients in each group.

Interpretation: ETP for rivaroxaban did not reach the non-inferiority threshold, but as there was no increase in thrombotic risk compared with standard-intensity warfarin, this drug could be an effective and safe alternative in patients with antiphospholipid syndrome and previous venous thromboembolism.

Funding: Arthritis Research UK, Comprehensive Clinical Trials Unit at UCL, LUPUS UK, Bayer, National Institute for Health Research Biomedical Research Centre.

Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

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Figures

Figure 1
Figure 1

Trial profile LLOD=lower limit of detection.

Figure 2
Figure 2

Thrombin generation parameters at baseline (left) and day 42 (right) Solid lines indicate medians, dotted lines indicate limits of normal ranges. NR=normal range. Warfarin (W)=patients receiving warfarin at baseline who continued taking warfarin after randomisation. Warfarin (R)=patients receiving warfarin at baseline who were switched to rivaroxaban at randomisation.

Figure 3
Figure 3

Thrombograms for median (25th and 7th percentiles) ETP values in RAPS, compared with a typical normal control value (A) Patients taking warfarin. (B) Patients taking rivaroxaban. ETP=endogenous thrombin potential. RAPS=the Rivaroxaban in Antiphospholipid Syndrome trial.

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References

    1. Erkan D, Aquiar C, Andrade D. 14th International Congress in Antiphospholipid Antibodies Task Force report on antiphospholipid syndrome treatment trends. Autoimmun Rev. 2014;13:685–696. - PubMed
    1. Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus. 2011;20:206–218. - PubMed
    1. Ruiz-Irastorza G, Egurbide MV, Ugalde J, Aguirre C. High impact of antiphospholipid syndrome on irreversible organ damage and survival of patients with systemic lupus erythematosus. Arch Intern Med. 2004;164:77–82. - PubMed
    1. Genetic and Rare Diseases Information Center (GARD) Antiphospholipid syndrome. May 25, 2016. https://rarediseases.info.nih.gov/gard/5824/antiphospholipid-syndrome/re... (accessed July 11, 2016).
    1. Andreoli L, Chighizola CB, Banzato A. Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction and deep vein thrombosis: a critical review of the literature. Arthritis Care Res (Hoboken) 2013;65:1869–1873. - PubMed

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