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Elevated International Normalized Ratio and Mortality in Hospitalized Patients Treated with Direct Oral Anticoagulants - 29/01/24

Doi : 10.1016/j.amjmed.2023.10.023 
Orly Efros, MD, MHA a, b, , Aya Berman, MD c, d, Gili Kenet, MD a, b, e, Aharon Lubetsky, MD a, b, Alon Doron, MD b, Gadi Shlomai, MD b, f, g, Eyal Klang, MD b, h, Shelly Soffer, MD d, i, Noam Barda, MD, PhD h, j, k, Avshalom Leibowitz, MD b, g
a National Hemophilia Center and Thrombosis & Hemostasis Institute, Sheba Medical Center, Ramat Gan, Israel 
b School of Medicine, Faculty of Medicine, Tel Aviv University, Israel 
c Dan Petah-Tikva District at Clalit Health Services, Petah-Tikva, Israel 
d Ben-Gurion University of the Negev, Be'er Sheva, Israel 
e Amalia Biron Research Institute of Thrombosis & Hemostasis 
f The Division of Endocrinology, Diabetes, and Metabolism 
g Department of Internal Medicine “D” and Hypertension Unit 
h Arc Innovation Center, Sheba Medical Center, Ramat-Gan, Israel 
i Internal Medicine B, Assuta Medical Center, Ashdod, Israel 
j Software and Information Systems Engineering 
k Epidemiology, Biostatistics and Community Health Services, Ben-Gurion University of the Negev, Be'er Sheva, Israel 

Requests for reprints should be addressed to Orly Efros, MD, MHA, National Hemophilia Center and Thrombosis & Hemostasis Institute, Sheba Medical Center, Derech Sheba 2, Ramat Gan 52621, Israel.National Hemophilia Center and Thrombosis & Hemostasis InstituteSheba Medical CenterDerech Sheba 2Ramat Gan52621Israel

Abstract

Background

Direct oral anticoagulants (DOACs) are associated with a prolongation of the prothrombin time and an increased international normalized ratio (INR). The clinical significance of these changes is unclear. This study aimed to examine the association between an elevated INR on admission and in-hospital death and long-term survival in patients treated with DOACs.

Methods

Data were retrospectively retrieved from records of hospitalized patients at the Sheba Medical Center between November 2008 and July 2023. Patients were selected based on DOAC treatment, coagulation profile, and INR test done within 48 hours of hospitalization. The outcomes were in-hospital mortality and mortality in the year following hospitalization.

Results

The study included 11,399 hospitalized patients treated with DOACs. Patients with elevated INR had a 180% higher risk of in-hospital mortality (adjusted odds ratio 2.80; 95% confidence interval, 2.30-3.39) and a 57% increased risk of death during the following year (adjusted hazard ratio 1.57; 95% confidence interval, 1.44-1.71). Similar results were observed in subgroup analyses for each DOAC.

Conclusions

An elevated INR on admission is associated with a higher risk for in-hospital death and increased risk for mortality during the first year following hospitalization in hospitalized patients treated with DOACs. This highlights that elevated INR levels in patients on DOACs should not be dismissed as laboratory variations due to DOAC treatment, as they may serve as a prognostic marker.

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Keywords : Direct oral anticoagulants, In-hospital mortality, International normalized ratio


Esquema


 Funding: The authors received no financial support for the research, authorship, or publication of this article.
 Conflicts of Interest: GK receives research support from Pfizer and consultancy/lectures from Bayer and Pfizer; AL receives research support from Pfizer and consultancy/lectures from Bayer, Pfizer, and Boehringer-Ingelheim. All other authors declare that they have no relevant conflicts of interest.
 Authorship: OE conceived and designed the research, interpreted the results, and wrote the manuscript; GK, A Lubetsky, AD, and GS contributed to the interpretation of the results and to the manuscript editing; AB contributed to the manuscript editing; EK contributed to data collection and to manuscript editing; SS contributed to the study design and to manuscript editing; NB contributed to the study design, data collection, statistical analysis, interpretation of the results, and to the writing of the manuscript; A Leibowitz contributed to study design, interpretation of the results, and to the writing of the manuscript.


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Vol 137 - N° 2

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