Contemporary trend of reduced-dose non-vitamin K anticoagulants in Japanese patients with atrial fibrillation: A cross-sectional analysis of a multicenter outpatient registry

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used to prevent stroke in non-valvular atrial fibrillation (NVAF) patients. Stringent monitoring is not required for NOACs, albeit dose adjustments are needed based on specific patient factors, such as renal function, body weight and age, or concomitant medications. We investigated the NOAC dosing patterns and evaluated the predictors of the non-standardized dose reduction (NSDR). Methods: A total of 2452 newly diagnosed NVAF patients were consecutively recruited from secondary- and tertiary-care hospitals between 2012 and 2017. The NOAC doses were classified as one of three: (1) full dose; (2) standardized dose reduction (SDR); or (3) NSDR, consistent with Japanese package inserts. Results: Overall, 66.8% (N = 1637) of the NVAF patients (median age: 69 years, interquartile range [IQR]: 60–76; 70% male; median CHA₂DS₂-VASc score of 2, IQR: 1–3) received NOACs. NOAC use dramatically increased during the study period (51.2% in 2012–13 to 74.4% in 2016–17). The percentages of SDR and NSDR were 19.6% and 14.4%, respectively; a proportion of SDR and NSDR did not alter drastically. Older age, concomitant antiplatelet therapy, impaired renal function, and prior heart failure or left ventricular dysfunction were independently associated with NSDR. Of note, patients with a high risk (CHA₂DS₂-VASc score ≥2) had the highest proportion of NSDRs. Conclusions: Nearly half of the NOAC dose reductions in our registry were deemed “non-standardized,” which were seen mostly in patients at significant risk for ischemic stroke. The physician's apprehension regarding excessive bleeding under NOAC use should be appropriately balanced with concern for an increased risk of embolic events.