Effectiveness and Safety of Off-label Dosing of Non–vitamin K Antagonist Anticoagulant for Atrial Fibrillation in Asian Patients

• Published in: Scientific reports Vol. 10; no. 1; p. 1801
• Main Authors: Lee, Kwang-No, Choi, Jong-Il, Boo, Ki Yung, Kim, Do Young, Kim, Yun Gi, Oh, Suk-Kyu, Baek, Yong-Soo, Lee, Dae In, Roh, Seung-Young, Shim, Jaemin, Kim, Jin Seok, Kim, Young-Hoon
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.02.2020; Nature Publishing Group
• Subjects: 692/4019/592/75/29/1309; 692/617/375/534; Aged; Aged, 80 and over; Anticoagulants; Anticoagulants - adverse effects; Anticoagulants - therapeutic use; Asian Continental Ancestry Group; Atrial Fibrillation - complications; Atrial Fibrillation - drug therapy; Bleeding; Cardiac arrhythmia; Dosage; Female; Fibrillation; Humanities and Social Sciences; Humans; Male; Middle Aged; multidisciplinary; Off-Label Use; Retrospective Studies; Science; Science (multidisciplinary); Thromboembolism; Thromboembolism - prevention & control; Treatment Outcome; Vitamin K; Warfarin; Warfarin - adverse effects; Warfarin - therapeutic use
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-58665-5

Non–vitamin K antagonist anticoagulants (NOACs) have been used to prevent thromboembolism in patients with atrial fibrillation (AF) and shown favorable clinical outcomes compared with warfarin. However, off-label use of NOACs is frequent in practice, and its clinical results are inconsistent. Furthermore, the quality of anticoagulation available with warfarin is often suboptimal and even inaccurate in real-world data. We have therefore compared the effectiveness and safety of off-label use of NOACs with those of warfarin whose anticoagulant intensity was accurately estimated. We retrospectively analyzed data from 2,659 and 3,733 AF patients at a tertiary referral center who were prescribed warfarin and NOACs, respectively, between 2013 and 2018. NOACs were used at off-label doses in 27% of the NOAC patients. After adjusting for significant covariates, underdosed NOAC (off-label use of the reduced dose) was associated with a 2.5-times increased risk of thromboembolism compared with warfarin, and overdosed NOAC (off-label use of the standard dose) showed no significant difference in either thromboembolism or major bleeding compared with warfarin. Well-controlled warfarin (TTR ≥ 60%) reduced both thromboembolism and bleeding events. In conclusion, the effectiveness of NOACs was decreased by off-label use of the reduced dose.