Current Real‐World Status of Off‐Label Under‐ and Over‐Dose of Direct Oral Anticoagulants After Atrial Fibrillation Ablation

Figures

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  Figure 1. Flow diagram of enrolled patients. DOAC; direct oral anticoagulant, OAC; oral anticoagulant. * Patients who used a method of administration that violated the package insert.

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  Figure 2. The proportions of dose categories for each DOAC. The numbers in the bars represent the number of patients. DOAC, direct oral anticoagulant.

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  Figure 3. Stratified analyses according to the thromboembolic and bleeding risk scores. (A) CHADS2 score 0–1 or ≥ 2. (B) CHA2DS2‐VASc score 0–2 or ≥ 3. (C) CHA2DS2‐VA score 0–1 or ≥ 2. (D) HELT‐E2S2‐score 0–1 or ≥ 2. (E) HAS‐B(L)ED score 0–2 or ≥ 3. The numbers in the bars represent the number of patients and (%). * p < 0.05.

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  Figure 4. Kaplan–Meier plot of the time to the first major adverse events adjudicated. The incidence of major adverse events (ischemic stroke/systemic embolic events or major bleeding events) were separately analyzed during the perioperative period (during and up to 30 days after catheter ablation) and during the remote period (from 31 days and up to 1 year after catheter ablation). (A) The cumulative event rates of ischemic stroke/systemic embolic events. Thromboembolic event rates were similarly low in each categorized dose group during both the perioperative and remote periods. (B) The cumulative event rates of major bleeding. Major bleeding event rates during the periprocedural period were high in all categorized dose groups. The major bleeding event rate at 1 year in off‐label overdose group was significantly higher compared with on‐label standard dose group.

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  Figure 5. Missing dose reduction criteria in off‐label overdose for each DOAC. The numbers represent the number of patients. BW, body weight; CrCl, creatinine clearance; Cre, creatinine; GI, gastrointestinal; P‐gp, p‐glycoprotein.

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  Figure 6. Kaplan–Meier plot of the time to the first major adverse events adjudicated. The incidence of major adverse events (ischemic stroke/systemic embolic events or major bleeding events) were separately analyzed during the late period (from 90 days and up to 1 year after catheter ablation). (A) The cumulative event rates of ischemic stroke/systemic embolic events in patients who discontinued DOACs beyond 90 days after AF ablation. No thromboembolic events were observed in each categorized dose group. (B) The cumulative event rates of major bleeding in patients who continued DOACs. The major bleeding event rate at 1 year in off‐label overdose group was significantly higher compared with on‐label reduced‐dose group.