Author + information
- Received March 12, 2018
- Revision received April 12, 2018
- Accepted April 17, 2018
- Published online July 9, 2018.
- Sharon W.Y. Law, MPharma,
- Wallis C.Y. Lau, PhDa,b,
- Ian C.K. Wong, PhDa,b,
- Gregory Y.H. Lip, MDc,d,
- Michael T. Mok, MBBSe,f,
- Chung-Wah Siu, MDg and
- Esther W. Chan, PhDa,∗ (, )@HKUniversity@unibirmingham
- aCentre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
- bResearch Department of Practice and Policy, UCL School of Pharmacy, London, United Kingdom
- cInstitute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
- dAalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- eDepartment of Cardiology, University Hospital Geelong, Geelong, Victoria, Australia
- fSchool of Medicine, Deakin University, Geelong, Victoria, Australia
- gCardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China
- ↵∗Address for correspondence:
Dr. Esther W. Chan, Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Office 02-08, 2/F Laboratory Block, 21 Sassoon Road, Hong Kong SAR, China.
Background Women with atrial fibrillation are at a higher risk of stroke, despite treatment with warfarin. It is unclear if women treated with direct oral anticoagulants (DOACs) have better clinical outcomes, especially when considering the quality of anticoagulation control of warfarin.
Objectives This study compared the effectiveness and safety outcomes of DOACs versus warfarin in men and women with stratifications for anticoagulation control.
Methods Patients newly diagnosed with atrial fibrillation and prescribed oral anticoagulants during 2010 to 2015 were identified using the Hong Kong clinical database. Propensity score matching was performed in men and women separately. Further analysis was conducted to stratify warfarin users according to their anticoagulation control. Cox regression was used to compare the risk of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding, and all-cause mortality in the specific sex.
Results There were 4,972 men and 4,834 women successfully matched in our cohort. Compared with warfarin, DOAC use was associated with a lower risk of ICH (hazard ratio [HR]: 0.16; 95% confidence interval [CI]: 0.06 to 0.40) and all-cause mortality (HR: 0.55; 95% CI: 0.39 to 0.77) in women but not in men. The treatment by sex interaction was significant for ICH only, and a significantly lower risk of ICH remained in the DOAC group when compared with warfarin users with good anticoagulation control (HR: 0.13; 95% CI: 0.02 to 1.00) among women only. The risks of ischemic stroke or systemic embolism and gastrointestinal bleeding with DOACs versus warfarin were comparable in both sexes.
Conclusions DOACs were associated with a lower risk of ICH and all-cause mortality in women only, where the association of lower ICH risk remained when compared with warfarin users with good anticoagulation control.
Dr. Wong has received research funding from the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, Bristol-Myers Squibb, Pfizer, and Janssen, a Division of Johnson & Johnson. Dr. Lip has served as a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo; and has served on the speakers bureau for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. Dr. Chan has received research funding from Research Grants Council of the University Grants Committee in the Hong Kong Special Administrative Region, Narcotics Division of the Security Bureau of The Government of the Hong Kong Special Administrative Region, Research Fund Secretariat of the Food and Health Bureau of The Government of the Hong Kong Special Administrative Region the Research Fund Secretariat of the Food and Health Bureau the Government of the Hong Kong Special Administrative Region, Bristol-Myers Squibb, Pfizer, and Janssen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 12, 2018.
- Revision received April 12, 2018.
- Accepted April 17, 2018.
- 2018 American College of Cardiology Foundation
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