Peak plasma concentration elevation over time occurred more frequently with rivaroxaban (50.9%) than edoxaban (31.7%, p<0.05), while all FXa inhibitors maintained normal fibrin monomer complex levels.
Observational (n=268)
Yes
Do rivaroxaban, apixaban, and edoxaban maintain stable coagulation activity despite variations in drug plasma concentration in outpatients with NVAF?
Once-daily FXa inhibitors maintain normal coagulation activity without daily variations despite wide peak-to-trough plasma concentration variations, indicating a low risk of thrombotic events comparable to twice-daily regimens.
Absolute Event Rate: 50.9% vs 31.7%
p-value: p=<0.05
Background: The therapeutic effects of oral anticoagulant drugs for nonvalvular atrial fibrillation (NVAF) suggest that the three factor Xa (FXa) inhibitors may have distinct safety profiles, though this is not yet fully conclusive. This study investigated the current dosing of rivaroxaban, apixaban, and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity from the viewpoint of the safety. Methods and results: This multicenter clinical study monitored the drug PC and two coagulation biomarkers (fibrinogen and fibrin monomer complex FMC) at peak and trough timing in 268 outpatients taking rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted based on the dose-adjustment criteria of each drug. Referencing our previous study, peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (rivaroxaban, n = 3; apixaban, n = 2; edoxaban, n = 3) in whom bleeding events occurred. Among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels, reflecting thrombin activity, remained within the normal range (<6.1 µg/mL) regardless of PC variations. These results indicated that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and dosing frequency. Regarding the change over time in peak PC, the elevation over time developed more in rivaroxaban (29/57; 50.9%, p < 0.05) than in edoxaban (32/101; 31.7%), and rivaroxaban tended to accumulate more than edoxaban. Conclusions: Although drug PC levels of once-daily FXa inhibitors widely varied from peak to trough, FMC levels were maintained within the normal range without daily variations. Rivaroxaban also tended to accumulate over time. The results indicate the low risk of thrombotic events with once-daily FXa inhibitors and its correspondence to the twice-daily regimen.
Suwa et al. (Fri,) conducted a observational in Nonvalvular atrial fibrillation (n=268). Rivaroxaban, apixaban, and edoxaban was evaluated on Elevation over time in peak plasma concentration (p=<0.05). Peak plasma concentration elevation over time occurred more frequently with rivaroxaban (50.9%) than edoxaban (31.7%, p<0.05), while all FXa inhibitors maintained normal fibrin monomer complex levels.