Background 

Limited real-world data are available regarding the outcome of patients treated with inappropriate dose of nonvitamin-K antagonist oral anticoagulants (NOACs).

Objective 

To assess the prevalence and factors associated with inappropriate dose prescription of NOACs and to evaluate adverse events that come from this inappropriate prescription.

Methods 

Single-center multidisciplinary registry including nonvalvular atrial fibrillation patients treated with NOACs. Based on guidelines criteria for dose reduction, two subcohorts were defined as treated with appropriate or inappropriate NOACs dose. Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox–Mantel test.

Results 

A total of 760 nonvalvular atrial fibrillation patients were included; 32% patients were treated with dabigatran, 34% with apixaban, 24% with rivaroxaban and 10% with edoxaban. An inappropriate dose was prescribed in 96 patients (12.6%), and in most cases (68%) it was too low. Rivaroxaban (15%) and apixaban (18.5%) were the most frequently prescribed with an inappropriate dose. Patients treated with an inappropriate dose were elderly people, with low-creatinine clearance value, who had experienced previous bleeding and with a high CHADS2 VASc score. In 2 years, a trend for higher numbers of thromboembolic events (5.2 vs. 3.3%, P = 0.348) and less major bleeding (2.1 vs. 4.2%, P = 0.316) has been observed in patients with inappropriate NOACs prescriptions.

Conclusion 

Nearly 13% of patients were treated with an inappropriate dose of NOACs, in this single-center study. A trend for higher numbers of thromboembolic events was observed in these patients. The results should be considered as hypothesis generating.

中文翻译：

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非维生素K拮抗剂口服抗凝剂剂量不当：非瓣膜性房颤患者的患病率及其对临床结局的影响

背景 

关于使用不适当剂量的非维生素K拮抗剂口服抗凝剂（NOAC）治疗的患者的治疗结果，有限的真实世界数据可用。

目的 

评估与NOAC剂量处方不当相关的患病率和因素，并评估这种不适当的处方引起的不良事件。

方法 

单中心多学科注册中心，包括接受NOAC治疗的非瓣膜性房颤患者。根据减少剂量的指导标准，将两个亚人群定义为接受适当或不适当的NOAC剂量治疗。主要疗效终点为2年血栓栓塞事件发生率。主要安全终点为2年大出血率。使用Cox-Mantel检验比较各组之间的无事件生存曲线。

结果 

总共包括760名非瓣膜性心房颤动患者。32％的患者接受达比加群，34％的阿哌沙班，24％的利伐沙班治疗和10％的埃多沙班治疗。的不适当的剂量是规定在96名患者（12.6％），并且在大多数情况下（68％）它是太低了。利伐沙班（15％）和阿哌沙班（18.5％）是最常见的处方，剂量不当。剂量不合适的患者是肌酐清除率较低，曾经历过大出血，CHADS2 VASc评分较高的老年人。在2年内，血栓栓塞事件的发生率呈上升趋势（5.2比3.3％，P = 0.348），大出血次数减少（2.1 vs. 4.2％，P = 0.316）在使用不合适的NOAC处方的患者中被观察到。

结论 

在这项单中心研究中，近13％的患者接受了不适当剂量的NOAC治疗。在这些患者中观察到血栓栓塞事件数量增加的趋势。结果应被视为产生假设。