BACKGROUND: Among patients hospitalized for atrial fibrillation, the frequency of off-label direct oral anticoagulant (DOAC) dosing, associated factors, hospital-level variation, and temporal trends in contemporary practice are unknown. METHODS: Using the Get With The Guidelines–Atrial Fibrillation registry, patients admitted from January 1, 2014, to March 31, 2020, and discharged on DOACs were stratified according to receipt of underdosing, overdosing, or recommended dosing. Factors associated with off-label dosing (defined as underdosing or overdosing) were identified using logistic regression. Median odds ratio (OR) and time-series analyses were used to assess hospital-level variation and temporal trends, respectively. RESULTS: Of 22 470 patients (70.1±12.1 years, 48.1% female, 82.5% White) prescribed a DOAC at discharge from hospitalization for atrial fibrillation (66% apixaban, 29% rivaroxaban, and 5% dabigatran), underdosing occurred among 2006 (8.9%), overdosing among 511 (2.3%), and recommended dosing among 19 953 (88.8%). The overall rate of off-label dosing was 11.2%. Patient-related factors associated with off-label dose included age (underdosing: OR, 1.06 per 1-year increase [95% CI, 1.06–1.07]; overdosing: OR, 1.07 per 1-year increase [95% CI, 1.06–1.09]), dialysis dependence (underdosing: OR, 5.50 [95% CI, 3.76–8.05]; overdosing: OR, 5.47 [95% CI, 2.74–10.88]), female sex (overdosing: OR, 0.79 [95% CI, 0.63–0.99]), and weight (overdosing: OR, 0.96 per 1-kg increase [95% CI, 0.95–1.00]). Across hospitals, the adjusted median OR for off-label DOAC dose was 1.45 (95% CI, 1.34–1.65; underdosing: OR, 1.52 [95% CI, 1.39–1.76]; overdosing: OR, 1.32 [95% CI, 1.20–1.84]), indicating significant hospital-level variation. Over the study period, recommended dosing significantly increased over time (81.9%–90.9%; P <0.0001 for trend) with a corresponding decline in underdosing (14.4%–6.6%; P <0.0001 for trend) and overdosing (3.8%–2.5%; P =0.001 for trend). CONCLUSIONS: Over 1 in 10 patients hospitalized for atrial fibrillation are discharged on an off-label DOAC dose with significant variation across hospitals. While the proportion of patients receiving recommended dosing has significantly improved over time, opportunities to improve DOAC dosing persist.

中文翻译：

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美国心房颤动住院患者直接口服抗凝剂的超说明书用药

背景：在因心房颤动住院的患者中，超说明书直接口服抗凝剂 (DOAC) 给药的频率、相关因素、医院水平变化以及当代实践中的时间趋势尚不清楚。 方法：使用“遵循指南-心房颤动登记”，对 2014 年 1 月 1 日至 2020 年 3 月 31 日入院并接受 DOAC 出院的患者根据剂量不足、用药过量或推荐剂量进行分层。使用逻辑回归确定与标签外给药（定义为给药不足或给药过量）相关的因素。中位比值比 (OR) 和时间序列分析分别用于评估医院水平的变化和时间趋势。 结果：22 470 名患者（70.1±12.1 岁，48.1% 女性，82.5% 白人）因心房颤动出院时开出 DOAC（66% 阿哌沙班、29% 利伐沙班和 5% 达比加群），2006 年发生剂量不足（8.9% ），其中 511 人（2.3%）服药过量，19 953 人（88.8%）建议服药。总体超说明书用药率为 11.2%。与超说明书剂量相关的患者相关因素包括年龄（剂量不足：OR，每 1 年增加 1.06 [95% CI，1.06–1.07]；用药过量：OR，每 1 年增加 1.07 [95% CI，1.06– 1.09]）、透析依赖（剂量不足：OR，5.50 [95% CI，3.76–8.05]；用药过量：OR，5.47 [95% CI，2.74–10.88]）、女性（用药过量：OR，0.79 [95% CI，95% CI） ，0.63–0.99]）和体重（用药过量：OR，每增加 1 公斤 0.96 [95% CI，0.95–1.00]）。在各医院中，超说明书 DOAC 剂量的调整后中位 OR 为 1.45（95% CI，1.34–1.65；剂量不足：OR，1.52 [95% CI，1.39–1.76]；用药过量：OR，1.32 [95% CI，1.20 –1.84]），表明医院级别存在显着差异。在研究期间，推荐剂量随时间显着增加（81.9%–90.9%；磷<0.0001 趋势），剂量不足相应下降（14.4%–6.6%；磷<0.0001 趋势）和过量（3.8%–2.5%；磷=0.001（趋势）。 结论：超过十分之一的因心房颤动住院的患者在出院时服用了超说明书剂量的 DOAC，但各医院之间存在显着差异。虽然接受推荐剂量的患者比例随着时间的推移显着提高，但改善 DOAC 剂量的机会仍然存在。