Abstract Number: PB2046
Meeting: ISTH 2020 Congress
Background: Rivaroxaban is a direct oral anticoagulant with similar efficacy to vitamin K antagonists in non-valvular atrial fibrillation (NVAF). Recent studies, including the landmark COMPASS trial, demonstrate that Rivaroxaban possesses cardiovascular protective and anti-inflammatory properties, however, underlying mechanisms remain poorly understood. The effects of Rivaroxaban on circulating pro-inflammatory extracellular vesicles (EVs) are currently unknown. We hypothesize that EV profiles differ in NVAF patients treated with Rivaroxaban compared to those treated with warfarin.
1. To characterize the effects of Rivaroxaban on circulating EV concentration and size in NVAF patients.
2. To perform comparative proteomic analysis of EVs from NVAF patients treated with Rivaroxaban and warfarin, respectively.
Methods: Plasma from Rivaroxaban (n=8) or matched warfarin (n=13) treated NVAF patients was obtained with informed consent. Vesicle-distribution profiles were acquired using Nanoparticle Tracking Analysis and flow cytometry. Label-free quantitative proteomic analysis was also performed, and platelet activation was assessed.
Results: We observed an overall reduction in circulating EV levels in Rivaroxaban-treated patients compared to warfarin (2.4-fold reduction; p=0.005). Quantitative proteomic analysis of enriched EVs revealed 103 differential proteins between the two patient cohorts. Strikingly, EVs from Rivaroxaban-treated patients exhibited a profound decrease in highly pro-inflammatory protein expression and complement factors, together with increased expression of negative regulators of inflammatory pathways. Moreover, we also found a reduction in circulating levels of platelet activation markers in Rivaroxaban-treated patients which negatively correlated with the patient’s time on treatment.
Conclusions: Collectively, these data demonstrate that NVAF patients anticoagulated with Rivaroxaban (compared with warfarin) exhibit both a reduced pro-inflammatory state and evidence of reduced platelet activation. These findings are of translational relevance towards characterising the cardioprotective and anti-inflammatory mechanisms associated with Rivaroxaban therapy.
To cite this abstract in AMA style:Weiss L, Szklanna PB, Uhrig W, Ewins K, Keaney J, Prendiville T, Kelliher S, Hanley C, Lennon Á, Dillion E, Blanco A, Murphy S, Ní Áinle F, Maguire PB. Non-Valvular Atrial Fibrillation Patients Anticoagulated with Rivaroxaban Compared with Warfarin Exhibit Attenuated Plasma Platelet Activation Markers and Pro-Inflammatory Extracellular Vesicle Proteomic Signatures [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/non-valvular-atrial-fibrillation-patients-anticoagulated-with-rivaroxaban-compared-with-warfarin-exhibit-attenuated-plasma-platelet-activation-markers-and-pro-inflammatory-extracellular-vesicle-proteo/. Accessed December 5, 2021.
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