Clinical outcomes in elderly atrial fibrillation patients at increased bleeding risk treated with very low dose vs. regular-dose non-vitamin K antagonist oral anticoagulants: a nationwide cohort study

Author:

Chan Yi-Hsin1234,Chao Tze-Fan56ORCID,Chen Shao-Wei27ORCID,Lee Hsin-Fu289,Li Pei-Ru10,Yeh Yung-Hsin12,Kuo Chi-Tai12,See Lai-Chu101112ORCID,Lip Gregory Y H1314

Affiliation:

1. The Cardiovascular Department, Chang Gung Memorial Hospital at Linkou , Taoyuan City 33305 , Taiwan

2. College of Medicine, Chang Gung University , Taoyuan City 33302 , Taiwan

3. School of Traditional Chinese Medicine, College of Medicine, Chang-Gung University , Taoyuan City 33302 , Taiwan

4. Microscopy Core Laboratory, Chang Gung Memorial Hospital at Linkou , Taoyuan 33305 , Taiwan

5. Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital , Taipei 112304 , Taiwan

6. Institute of Clinical Medicine, Cardiovascular Research Center, National Yang Ming Chiao Tung University , Taipei , Taiwan

7. Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University , Taoyuan City , Taiwan

8. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University , Taoyuan City, Taiwan

9. New Taipei City Municipal Tucheng Hospital (Chang Gung Memorial Hospital , Tucheng Branch), New Taipei City 236017 , Taiwan

10. Department of Public Health, College of Medicine, Chang Gung University , Taoyuan City 33302 , Taiwan

11. Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University , Taoyuan City 33302 , Taiwan

12. Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou , Taoyuan City 33305 , Taiwan

13. Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital , Liverpool , UK

14. Department of Clinical Medicine, Aalborg University , Denmark

Abstract

Abstract Aims The Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial showed that edoxaban at a very low dosage (VLD) of 15 mg/day was more effective than a placebo at preventing stroke/systemic embolism without significantly increasing the risk of serious bleeding. We aimed to compare the effectiveness and safety for VLD non-vitamin K antagonist oral anticoagulants (NOACs) [edoxaban 15 mg o.d., dabigatran 110 or 150 o.d., apixaban 2.5 mg o.d., or rivaroxaban 10 mg (without the diagnosis of chronic kidney disease) or <10 mg o.d.] vs. regular-dosage (RD) NOACs (edoxaban 60/30 mg o.d. or other labeling-dosage NOACs) among a real-world cohort of elderly atrial fibrillation (AF) population similar to the ELDERCARE-AF cohort. Methods and results In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database (NHIRD), we identified a total of 7294 and 4151 consecutive AF patients aged 80 years or older with a CHADS2 (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient ischemic attack (2 points) score ≥2 who met the enrollment criteria (generally similar to ELDERCARE-AF) taking VLD and RD NOACs from 1 June 2012 to 31 December 2019, respectively. Propensity-score stabilized weighting (PSSW) was used to balance covariates across study groups. Patients were followed up from the first date of prescription for NOACs until the first occurrence of any study outcome, death, or until the end date of the study period (31 December 2020). After PSSW, VLD NOAC was associated with a comparable risk of ischemic stroke/systemic embolism and major bleeding but a higher risk of major adverse limb events (MALEs) requiring lower limb revascularization or amputation [hazard ratio (HR): 1.54, 95% confidential interval (CI): 1.09–2.18; P = 0.014), venous thrombosis (HR: 3.75, 95% CI: 1.56–8.97; P = 0.003), and all-cause mortality (HR: 1.21, 95% CI: 1.15–1.29; P <0.001) compared with RD NOACs. VLD NOACs showed worse outcomes in most net clinical outcome (NCO) benefits. The main result was consistent based on on-treatment analysis or accounting for death as a competing risk. In general, the advantage of NCOs for the RD NOACs over VLD NOACs persisted in most high-risk subgroups, consistent with the main analysis (P for interaction > 0.05). Conclusion Use of VLD NOACs was associated with a greater risk of arterial and venous thrombosis, death as well as the composite outcomes, when compared with that of RD NOAC in high-risk elderly AF patients at increased bleeding risk. Thromboprophylaxis with RD NOAC is still preferable over VLD NOAC for the majority of elderly AF patients at increased bleeding risk.

Funder

Ministry of Science and Technology

Chang Gung Memorial Hospital

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Cardiology and Cardiovascular Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3