Off-Label Dosing of Non-Vitamin K Antagonist Oral Anticoagulants and Adverse Outcomes: The ORBIT-AF II Registry.

Abstract Background Although non-vitamin K antagonist oral anticoagulants (NOACs) do not require frequent laboratory monitoring, each compound requires dose adjustments on the basis of certain clinical criteria. Objectives This study assessed the frequency of off-label NOAC doses among AF patients and the associations between off-label dose therapy and clinical outcomes in community practice. Methods We evaluated 5,738 patients treated with a NOAC at 242 ORBIT-AF II (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation phase II) sites. NOAC doses were classified as either underdosed or overdosed, consistent with Food and Drug Administration labeling. Longitudinal outcomes (median follow-up: 0.99 years) included stroke or systemic embolism, myocardial infarction, major bleeding (International Society of Thrombosis and Haemostasis criteria), cause-specific hospitalization, and all-cause mortality. Results Overall, 541 NOAC-treated patients (9.4%) were underdosed, 197 were overdosed (3.4%), and 5,000 were dosed according to U.S. labeling (87%). Compared with patients receiving the recommended dose, those who were receiving off-label doses were older (median: 79 and 80 years of age vs. 70 years of age, respectively; p  2 DS 2 -VASc scores (96% and 97% ≥2 vs. 86%, respectively; p  4 vs. 11%, respectively; p  Conclusions A significant minority (almost 1 in 8) of U.S. patients in the community received NOAC doses inconsistent with labeling. NOAC over- and underdosing are associated with increased risk for adverse events. (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II [ORBIT-AF II]; NCT01701817 )