Interactions between rivaroxaban and antiphospholipid antibodies in thrombotic antiphospholipid syndrome

Arachchillage, Deepa R. J.; Mackie, Ian; Efthymiou, Maria; Isenberg, David; Machin, Samuel J.; Cohen, Hannah

doi:10.1111/jth.12917

Cited by 58 publications

(68 citation statements)

References 30 publications

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“…Indeed, in vitro, the effects of antiphospholipid antibodies on thrombin generation are limited to prolongation of lag time and time to peak thrombin generation 31 . Our exploratory post-hoc analysis showed no significant interactions between the effects of rivaroxaban and lupus anticoagulant positivity on thrombin generation.…”

Section: Discussionmentioning

confidence: 65%

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

Cohen

Hunt

Efthymiou

et al. 2016

The Lancet Haematology

355

252

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SummaryBackgroundRivaroxaban is established for the treatment and secondary prevention of venous thromboembolism, but whether it is useful in patients with antiphospholipid syndrome is uncertain.MethodsThis 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.FindingsOf 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.InterpretationETP 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.FundingArthritis Research UK, Comprehensive Clinical Trials Unit at UCL, LUPUS UK, Bayer, National Institute for Health Research Biomedical Research Centre.

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Section: Discussionmentioning

confidence: 65%

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

Cohen

Hunt

Efthymiou

et al. 2016

The Lancet Haematology

355

252

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“…False positivity in RIV-treated patients was illustrated previously [21][22][23][24]. Martinuzzo et al found that most RIV-treated patients presented prolonged dRVVT screen results without correction with PNP and mostly LAC ratios above the CO [21].…”

Section: Discussionmentioning

confidence: 93%

“…Martinuzzo et al found that most RIV-treated patients presented prolonged dRVVT screen results without correction with PNP and mostly LAC ratios above the CO [21]. Arachillage et al determined that false-positive LAC results were obtained starting from 250 ng/mL on using two dRVVT systems [22]. Merriman et al performed LAC analysis on 21 RIV-treated non-APS patients, which yielded a prolonged screen, mix and LAC ratio.…”

Section: Discussionmentioning

confidence: 97%

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Dilute Russell’s viper venom time reagents in lupus anticoagulant testing: a well-considered choice

Depreter

Devreese

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…TVT/ECT was considered positive if the TVT was prolonged and the normalized TVT/ECT ratio was >1.20. The TVT/ECT ratio cut‐off of 1.20 was established locally in accordance with CLSI guidelines…”

Section: Methodsmentioning

confidence: 99%

Comparison of real world and core laboratory lupus anticoagulant results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository

Efthymiou

Mackie

Lane

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Variability remains a challenge in lupus anticoagulant (LA) testing. Objective To validate LA test performance between Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Core laboratories and examine agreement in LA status between Core and local/hospital laboratories contributing patients to this prospective registry. Methods Five Core laboratories used the same reagents, analyzer type, protocols, and characterized samples for LA validation. Non‐anticoagulated registry samples were retested at the corresponding regional Core laboratories and anticoagulated samples at a single Core laboratory. Categorical agreement and discrepancies in LA status between Core and local/hospital laboratories were analyzed. Results Clotting times for the reference/characterized plasmas used for normalized ratios were similar between Core laboratories (CV <4%); precision and agreement for LA positive/negative plasma were similar (all CV ≤5%) in the four laboratories that completed both parts of the validation exercise; 418 registry samples underwent LA testing. Agreement for LA positive/negative status between Core and local/hospital laboratories was observed in 87% (115/132) non‐anticoagulated and 77% (183/237) anticoagulated samples. However, 28.7% (120/418) of samples showed discordance between the Core and local/hospital laboratories or equivocal LA results. Some of the results of the local/hospital laboratories might have been unreliable in 24.7% (41/166) and 23% (58/252) of the total non‐anticoagulated and anticoagulated samples, respectively. Equivocal results by the Core laboratory might have also contributed to discordance. Conclusions Laboratories can achieve good agreement in LA performance by use of the same reagents, analyzer type, and protocols. The standardized Core laboratory results underpin accurate interpretation of APS ACTION clinical data.

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Interactions between rivaroxaban and antiphospholipid antibodies in thrombotic antiphospholipid syndrome

Cited by 58 publications

References 30 publications

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

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

Dilute Russell’s viper venom time reagents in lupus anticoagulant testing: a well-considered choice

Comparison of real world and core laboratory lupus anticoagulant results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository

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