Twice- or once-daily dosing of direct oral anticoagulants and gastrointestinal bleeding in patient with atrial fibrillation

Figures

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  Fig. 1. Theoretical pharmacokinetic profile of a drug. These schematic graphs illustrate the theoretical pharmacokinetic profile of a drug in serum and gastrointestinal lumen: a dose X administered once-daily (QD, black line), and a dose X/2 administered twice-daily (BID, red line). A) Taking proper regimen. B) Taking an extra tablet may result in a higher peak in the QD than in the BID regimen. C) A single miss of DOAC may deviate the concentration downward from the therapeutic range more severely in the QD regimens than in the BID regimens. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

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  Fig. 2. Patient selection flowchart. *A propensity score was calculated by a logistic regression model with the parameters of age, sex, body weight, antiplatelet use, hemoglobin, creatinine, diabetes mellitus, hypertension, dyslipidemia, a history of heart failure, a history of bleeding, a history of stroke, atherosclerosis, and liver dysfunction. Abbreviations: NVAF = non-valvular atrial fibrillation; DOAC = direct oral anticoagulants; BID = twice-daily dosing; QD = once-daily dosing.

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  Fig. 3. Kaplan-Meier estimates for gastrointestinal bleeding. Kaplan-Meier analysis for gastrointestinal bleeding according to QD vs. BID regimens of DOAC in the propensity score-matched population. Patient with BID regimen group less frequently had gastrointestinal bleeding than those with QD regimen group (log-rank P < 0.0001). Abbreviations: GI = gastrointestinal; DOAC = direct oral anticoagulants; BID = twice-daily dosing; QD = once-daily dosing.

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  Fig. 4. Kaplan-Meier estimates for secondary endpoints. Kaplan-Meier analysis for secondary endpoints according to QD vs. BID regiments of DOAC in the propensity score-matched population. There was no significant difference between the BID regimen group and the QD regimen group in each endpoint in all death (A), stroke (B), and any bleeding (D). Patients with the QD regimens experienced major bleeding more frequently than those with the BID regimens (C) (log-rank P = 0.040). Abbreviations: DOAC = direct oral anticoagulants; BID = twice-daily dosing; QD = once-daily dosing.