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CC BY 4.0 · Thromb Haemost 2022; 122(06): 939-950
DOI: 10.1055/a-1669-4987
Coagulation and Fibrinolysis

Oral Anticoagulation Timing in Patients with Acute Ischemic Stroke and Atrial Fibrillation

Po-Yin Chang‡   *
1   Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Maryland, United States
,
Wei-Ting Wang  ‡   *
2   Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan
3   Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
4   School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
5   Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Wei-Lun Wu
6   Institute of Health and Welfare Policy, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Hui-Chin Chang
6   Institute of Health and Welfare Policy, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Chen-Huan Chen
4   School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
7   Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
8   Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Yi-Wen Tsai‡   *
6   Institute of Health and Welfare Policy, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Shih-Hwa Chiou
3   Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
4   School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
5   Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Gregory Y. H. Lip 
9   Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
10   Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
,
Hao-Min Cheng  ‡   *
2   Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan
3   Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
7   Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
8   Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan
11   Center for Evidence-based Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
,
Chern-En Chiang
2   Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei City, Taiwan
12   General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan
› Author Affiliations Funding None.
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Abstract

Background and Purpose Oral anticoagulants (OACs) prevent stroke recurrence and vascular embolism in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Based on empirical consensus, current guidance recommends a “1–3–6–12 days” rule to resume OACs after AIS. This study investigated the suitability of guideline-recommended timing for OAC initiation.

Methods Using data of 12,307 AF patients hospitalized for AIS, for the period 2012 to 2016, in Taiwan's National Health Insurance Research Database, we constructed a sequence of cohorts of OAC users and propensity score-matched nonusers, creating one cohort on each day of OAC initiation for 30 days since admission. Composite outcome included effectiveness (cardiovascular death, ischemic stroke, myocardial infarction, transient ischemic attack, systemic embolism, and venous thromboembolism) and safety (intracranial hemorrhage, gastrointestinal bleeding, and hematuria) outcomes. Comparing with nonusers, we examined the risks in the early OAC use (within 1–3–6–12 days) or guideline-recommended delayed use. Indirect comparison between the early and delayed use was conducted using mixed treatment comparison.

Results Across the AIS severity, the risks of composite or effectiveness outcome were lower in OAC users than nonusers, and the risks were similar between the early and delayed use groups. In patients with severe AIS, early OAC use was associated with an increased risk of safety outcome, with a hazard ratio (HR) of 1.67 (confidence interval [CI]: 1·30–2·13) compared with nonusers and a HR of 1.44 (CI: 0·99–2·09) compared with the delayed use.

Conclusion Our study findings support an early OAC initiation in AF patients with mild-to-moderate AIS and a routine delayed use of OACs can be considered in those with severe AIS to avoid a serious bleeding event.

Keywords

atrial fibrillation - acute ischemic stroke - oral anticoagulants - timing - stroke recurrence

Ethical Approval

The study protocol was approved by ethic committee of Taipei Veterans General Hospital.


Note

All authors confirm that they had full access to all the data in the study and accept responsibility to submit for publication. However, our study does not contain data from any individual. The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. The authors declare that they have no competing interests. This article reflects the views of the authors and does not represent the U.S. Food and Drug Administration's views or policies.


Author Contributions

C.-E.C., H.-M.C., and Y.-W.T. conceived and designed the research. Statistical analysis was performed by W.-L. Wu, P.-Y.C., W.-T.W., and H.-C.C.. W.-T.W., P.-Y.C., Y.-W.T., S.-H.C., and H.-M.C. drafted the article. C.-H.C. and C.-E.C. made critical revision of the article for key intellectual content. Each author contributed important intellectual content during article drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. H.-M.C., C.-H.C., C.-E.C., and Y.-W.T. undertake that this study has been reported honestly, accurately, and transparently, that no important aspects of the study have been omitted, and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.


* These authors contributed equally to this work. Note: The review process for this paper was fully handled by Christian Weber, Editor-in-Chief.


Supplementary Material



Publication History

Received: 02 June 2021

Accepted: 11 October 2021

Accepted Manuscript online:
14 October 2021

Article published online:
31 December 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
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