Effectiveness and Safety of Reduced and Standard Daily Doses of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation: A Cohort Study Using National Database Representing the Japanese Population

Abstract

Purpose To compare the effectiveness and safety of reduced or standard daily doses of direct oral anticoagulants (DOACs) with warfarin in Japanese patients with nonvalvular atrial fibrillation (NVAF). We used post-hoc analyses to identify patient groups that could benefit from reduced-dose DOACs. Patients and Methods Using the National Database of Health Insurance Claims and Specific Health Checkups of Japan, we identified 944,776 patients with NVAF who had started an oral anticoagulant after at least one year of non-use between April 2011 and March 2016. We matched patients taking any, reduced, or standard doses of DOACs 1:1 with those taking warfarin. We measured treatment effectiveness based on admission due to stroke or systemic embolism (S/SE) and safety based on admission due to any bleeding (defined as major bleeding, MB). We compared both outcomes between DOACs and warfarin using the Cox proportional hazards model. We used post-hoc analysis to match patients receiving reduced-dose DOACs to those receiving standard-dose DOACs and compared treatment effectiveness and safety. Results More than half of patients receiving DOACs used a reduced dose. The occurrences of S/SE and MB in patients receiving any, reduced, or standard doses of DOACs were equal to or lower than those receiving warfarin. In the post-hoc analysis, the risk of S/SE and MB was similar between reduced and standard doses of DOACs except for those with a history of cerebral infarction and CHA 2 DS 2 -VASc score ≥3, where the risk of S/SE was lower for reduced doses of any and individual DOACs. Conclusion Findings from the current study are consistent with recent Asian and global studies but different from most studies conducted in North America and Europe, where patients receiving a reduced dose of DOACs had an increased risk of S/SE. Future studies should test the reproducibility of results from the current study.

Safety and Effectiveness of Apixaban Versus Warfarin in Japanese Patients with Nonvalvular Atrial Fibrillation Stratified by Renal Function: A Retrospective Cohort Study

“…When oral anticoagulation is to be started in a patient with AF who is eligible for DOACs, the 2020 Japanese Circulation Society/Japanese Heart Rhythm Society guidelines recommend a DOAC in preference to warfarin (class I recommendation: evidence and/or general agreement that a given procedure or treatment is useful and effective) [12]. In a cohort study that used a national database representing the Japanese population, the annual number of new warfarin users declined 74% from fiscal year (FY) 2011 to FY 2015, whereas users of any DOAC increased by 6.8-fold (FY 2011: 26.7%; and FY 2015: 83.4%) [27]. The 2020 European Society of Cardiology guidelines recommend DOACs as the first choice for patients with CrCl ≥ 30 mL/min [28].…”

Trend of anticoagulant therapy in elderly patients with atrial fibrillation considering risks of cerebral infarction and bleeding

“…One of them used the prefecture-level the National Health Insurance database 10 and three of them used the Japan Medical Data Center (JMDC) database 11 – 13 , which did not include the patients 75 years or older. The recent two studies that also included old patients, one used the Japanese Diagnosis Procedure Combination (DPC) database including claim data of acute care hospitals 14 and the other used the National Database sampling dataset 15 , added findings on prescription patterns of DOACs. However, there have been no papers reporting the trend of prescriptions of DOACs stratified by risks of cerebral infarction and bleeding at the nation-level including old patients.…”