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Increased Levels of Platelets and Endothelial-Derived Microparticles in Patients With Non-Valvular Atrial Fibrillation During Rivaroxaban Therapy.

ABSTRACT: It is known that atrial fibrillation (AF) is associated with the procoagulant state. Several studies have reported an increase of circulating microparticles in AF, which may be linked to a hypercoagulable state, atrial thrombosis and thromboembolism. We evaluated in our study alterations in both platelet (PMP, CD42b) and endothelial-derived (EMP, CD144) microparticle levels on anticoagulant therapy with rivaroxaban in nonvalvular AF. After administration of rivaroxaban, PMP levels were increased (median, [IQR] 35.7 [28.8-47.3] vs. 48.4 [30.9-82.8] cells/µL; P = 0.012), along with an increase in EMP levels (14.6 [10.0-18.6] vs. 18.3 [12.9-37.1] cells/µL, P < 0.001). In the multivariable regression analysis, the independent predictor of post-dose change in PMPs was statin therapy (HR -0.43; 95% CI -0.75,-0.10, P = 0.011). The post-dose change in EMPs was also predicted by statin therapy (HR -0.34; 95% CI -0.69, -0.01, P = 0.046). This study showed an increase in both EMPs and PMPs at the peak plasma concentration of rivaroxaban. Statins have promising potential in the prevention of rivaroxaban-related PMP and EMP release. The pro-thrombotic role of PMPs and EMPs during rivaroxaban therapy requires further study.

SUBMITTER: Lenart-Migdalska A

PROVIDER: S-EPMC8155766 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo compare effectiveness and safety of warfarin and the direct oral anticoagulants (DOAC) dabigatran, rivaroxaban and apixaban in non-valvular atrial fibrillation in routine care.MethodsFrom nationwide registries, we identified treatment-naïve patients initiating warfarin, dabigatran, rivaroxaban or apixaban for non-valvular atrial fibrillation from July 2013 to December 2015 in Norway. We assessed prescription duration using reverse waiting time distribution. Adjusting for confounding in a Cox proportional hazards model, we estimated one-year risks for ischemic stroke, transient ischemic attack (TIA) or systemic embolism, major or clinically relevant non-major bleeding; intracranial; gastrointestinal; and other bleeding. We censored at switch of treatment or 365 days of follow-up.ResultsWe included 30,820 treatment-naïve patients. Compared to warfarin, the adjusted hazard ratios (HR) for ischemic stroke, TIA or systemic embolism were 0.96 (95% CI 0.71-1.28) for dabigatran, 1.12 (95% CI 0.87-1.45) for rivaroxaban and 0.97 (95% CI 0.75-1.26) for apixaban. Corresponding hazard ratios for major or clinically relevant non-major bleeding were 0.73 (95% CI 0.62-0.86) for dabigatran, 0.97 (95% CI 0.84-1.12) for rivaroxaban and 0.71 (95% CI 0.62-0.82) for apixaban. Statistically significant differences of other safety outcomes compared to warfarin were fewer intracranial bleedings with dabigatran (HR 0.28, 95% CI 0.14-0.56), rivaroxaban (HR 0.40, 95% CI 0.23-0.69) and apixaban (HR 0.56, 95% CI 0.34-0.92); fewer gastrointestinal bleedings with apixaban (HR 0.70, 95% CI 0.52-0.93); and fewer other bleedings with dabigatran (HR 0.67, 95% CI 0.55-0.81) and apixaban (HR 0.70, 95% CI 0.59-0.83).ConclusionAfter 1 year follow-up in treatment-naïve patients initiating oral anticoagulation for non-valvular atrial fibrillation, all DOACs were similarly effective as warfarin in prevention of ischemic stroke, TIA or systemic embolism. Safety from bleedings was similar or better, including fewer intracranial bleedings with all direct oral anticoagulants, fewer gastrointestinal bleedings with apixaban and fewer other bleedings with dabigatran and apixaban.

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Increased Levels of Platelets and Endothelial-Derived Microparticles in Patients With Non-Valvular Atrial Fibrillation During Rivaroxaban Therapy.

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