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Long-Term Clinical Outcomes of Underdosed Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Atrial Flutter

Authors :
Pradyumna Agasthi
Nirat Beohar
David R. Holmes
Mohamed Allam
Pattara Rattanawong
Sai Harika Pujari
Komandoor Srivathsan
Dan Sorajja
Win Kuang Shen
William K. Freeman
Ramila A. Mehta
Hicham El Masry
Farouk Mookadam
Eric H. Yang
Hasan Ashraf
Xiaoxi Yao
Anusha Shanbhag
Reza Arsanjani
Siva K. Mulpuru
Peter A. Noseworthy
Source :
The American Journal of Medicine. 134:788-796
Publication Year :
2021
Publisher :
Elsevier BV, 2021.

Abstract

Background Although direct oral anticoagulants (DOACs) have been shown to be effective at reducing the risk of stroke in patients with atrial fibrillation/flutter (AF), they are sometimes underdosed off-label to mitigate their associated higher bleeding risk. We sought to evaluate frequency and clinical outcomes of inappropriate underdosing of DOACS in patients with AF. Methods We conducted a study of subjects with AF who had a clinical indication for stroke prophylaxis (with a congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 47 years, sex category [CHA2DS2-VASc] of 2 or greater) and were prescribed 1 of the 4 clinically approved DOACs (apixaban, rivaroxaban, dabigatran, or edoxaban). We compared all-cause mortality, composite of stroke and systemic embolism, composite of myocardial infarction (MI), acute coronary syndromes (ACS), and coronary revascularization, and major bleeding between patients appropriately dosed and inappropriately underdosed. Results A total of 8125 patients met inclusion criteria, with a mean follow up of 2.2 ± 2 years. Of those, 1724 patients (21.2%) were inappropriately dosed. After adjusting for baseline variables, there was no difference in all-cause mortality, risk of stroke or systemic embolism, International Society on Thrombosis and Haemostasis (ISTH) major bleeding, or composite of myocardial infarction, acute coronary syndromes, or coronary revascularization between patients appropriately dosed and inappropriately underdosed. In subgroup analysis, only apixaban demonstrated an increased incidence all-cause mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.03-1.49) with inappropriate underdosing. There was no difference in the remaining clinical outcomes noted on subgroup analysis. Conclusion Underdosing of DOACs did not minimize risk of bleeding, systemic embolization or all-cause mortality in patients with AF. Inappropriate underdosing with apixaban in particular was associated with increased all-cause mortality.

Details

ISSN :
00029343
Volume :
134
Database :
OpenAIRE
Journal :
The American Journal of Medicine
Accession number :
edsair.doi.dedup.....0a208d3d438370669e4cbffc54f2c523
Full Text :
https://doi.org/10.1016/j.amjmed.2020.12.022