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      Safety and Efficacy of Direct Oral Anticoagulants vs Warfarin in Patients With Obesity and Venous Thromboembolism: A Retrospective Analysis

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          Abstract

          Background:

          Current venous thromboembolism guidelines recommend using direct oral anticoagulants (DOACs) over warfarin regardless of obesity status; however, evidence remains limited for the safety and efficacy of DOAC use in patients with obesity. This retrospective analysis sought to demonstrate the safety and efficacy of DOACs compared with warfarin in a diverse population of patients with obesity in light of current prescribing practices.

          Methods:

          A retrospective cohort study was conducted at a large academic health system between July 2014 and September 2019. Adults with an admission diagnosis of deep vein thrombosis (DVT) or pulmonary embolism, with weight greater than 120 kg or a body mass index greater than 40, and who were discharged on an oral anticoagulant were included. Outcomes included occurrence of a thromboembolic event (DVT, pulmonary embolism, or ischemic stroke), bleeding event requiring hospitalization, and all-cause mortality within 12 months following index admission.

          Results:

          Out of 787 patients included, 520 were in the DOAC group and 267 were in the warfarin group. Within 12 months of index hospitalization, thromboembolic events occurred in 4.23% of patients in the DOAC group vs 7.12% of patients in the warfarin group (hazard ratio, 0.6 [95% CI, 0.32-1.1]; P = .082). Bleeding events requiring hospitalization occurred in 8.85% of DOAC patients vs 10.1% of warfarin patients (hazard ratio, 0.93 [95% CI, 0.57-1.5]; P = .82). A DVT occurred in 1.7% and 4.9% of patients in the DOAC and warfarin groups, respectively (hazard ratio, 0.35 [95% CI, 0.15-0.84]; P = .046).

          Conclusion:

          No significant differences could be determined between DOACs and warfarin for cumulative thromboembolic or bleeding events, pulmonary embolism, ischemic stroke, or all-cause mortality. The risk of DVT was lower with apixaban and rivaroxaban. Regardless of patient weight or body mass index, physicians prescribed DOACs more commonly than warfarin.

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          Most cited references22

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          Antithrombotic Therapy for VTE Disease

          This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously.
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            Overweight, obesity, and the risk of recurrent venous thromboembolism.

            Excess body weight is a risk factor for a first venous thromboembolism. The impact of excess body weight on risk of recurrent venous thrombosis is uncertain. We studied 1107 patients for an average of 46 months after a first unprovoked venous thromboembolism and withdrawal of anticoagulant therapy. Excluded were pregnant patients, those requiring long-term antithrombotic treatment, and those who had a previous or secondary thrombosis, natural coagulation inhibitor deficiency, lupus anticoagulant, or cancer. Our study end point was symptomatic recurrent venous thromboembolism. A total of 168 patients had recurrent venous thromboembolism. Mean (SD) body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) was significantly higher among patients with recurrence than among those without recurrence: 28.5 (6.0) vs 26.9 (5.0) (P = .01). The relationship between excess body weight and recurrence was linear; the adjusted hazard ratio for each 1-point increase in BMI was 1.044 (95% confidence interval [CI], 1.013-1.076) (P < .001). Four years after discontinuation of anticoagulant therapy, the probability of recurrence was 9.3% (95% CI, 6.0%-12.7%) among patients of normal weight and 16.7% (95% CI, 11.0%-22.3%) and 17.5% (95% CI, 13.0%-22.0%) among overweight and obese patients, respectively. Compared with patients of normal weight, the hazard ratio of recurrence adjusted for age, sex, factor V Leiden, prothrombin G20210A mutation, high factor VIII levels, and type of initial venous thromboembolic event was 1.3 (95% CI, 0.9-1.9) (P = .20) among overweight patients and 1.6 (95% CI, 1.1-2.4) (P = .02) among obese individuals. The population attributable risk corresponding to excess body weight was 26.8% (95% CI, 5.3%-48.2%). Excess body weight is a risk factor of recurrent venous thromboembolism.
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              Trends and Variation in Oral Anticoagulant Choice in Patients with Atrial Fibrillation, 2010-2017

              Objective Since 2010, several non-vitamin K antagonist oral anticoagulants (NOACs) have been brought to the U.S. market, yet little is known regarding their evolving adoption for prophylaxis of atrial fibrillation (AF) related stroke. We examined temporal trends in choice of oral anticoagulants (OACs) among incident OAC users with AF and its association with patients’ demographic and clinical characteristics. Methods We conducted a serial cross-sectional analysis of medical and pharmacy claims for commercial and Medicare Advantage enrollees in a large, private, U.S. health plan. We identified 112,187 adults with nonvalvular AF starting OACs between October 2010 and March 2017. Multivariable logistic regression was used to examine the associations of patient characteristics with prescription of NOACs vs warfarin. Multinomial logistic regression with generalized logit link function was used to test the association of patient characteristics with choice among NOACs. Results The prescription of NOACs has increased dramatically since their introduction in October 2010. In the first quarter of 2017 (2017Q1), 7,502 patients started OACs, of whom 78.9% used NOACs and 21.1% warfarin. For NOACs, 3.8% used dabigatran, 25.0% rivaroxaban, and 50.1% apixaban. In multivariable analyses, factors associated with choice of NOACs vs warfarin included younger age, lower stroke or bleeding risk, fewer comorbidities, higher socioeconomic status, and prescription by cardiologists (all P <0.001). There was no sex difference in likelihood of filling NOACs vs warfarin in 2010Q4–2012 but women had higher odds of starting NOACs (odds ratio=1.19; 95% confidence interval=1.14–1.25) in 2015–2017Q1. Among NOAC users, the odds of apixaban prescription increased with age, female sex, stroke or bleeding risk, and comorbidities (all P <0.05). Conclusion NOAC prescriptions have increased substantially among incident OAC users with nonvalvular AF, predominantly driven by increased prescription of apixaban. Warfarin and apixaban were generally preferred for elderly, patients with higher stroke or bleeding risk, and those with more comorbidities.
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                Author and article information

                Journal
                Tex Heart Inst J
                Tex Heart Inst J
                thij
                The Texas Heart Institute Journal
                Texas Heart® Institute, Houston
                0730-2347
                1526-6702
                Jan-Jun 2024
                15 May 2024
                : 51
                : 1
                : e238260
                Affiliations
                [1 ]Department of Pharmacy, Houston Methodist Hospital, Houston, Texas
                [2 ]University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina
                [3 ]Department of Health Outcomes Research and Policy, Auburn University Harrison College of Pharmacy, Auburn, Alabama
                [4 ]Department of Pharmacy, Novant Health New Hanover Regional Medical Center, Wilmington, North Carolina
                Author notes
                Corresponding author: Zoe H. Tu, PharmD, 6565 Fannin St, Houston, TX, 77030 ( zhtu@ 123456houstonmethodist.org )
                Article
                10.14503/THIJ-23-8260
                11095664
                38748549
                1c50c871-774f-4c05-a4b1-56b7cf2805cd
                © 2024 The Authors. Published by The Texas Heart Institute ®

                This is an Open Access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use and distribution in any medium, provided the original work is properly cited, and the use is noncommercial.

                History
                Page count
                Pages: 7
                Categories
                Clinical Investigation

                anticoagulants,obesity,warfarin,venous thromboembolism,venous thrombosis,factor xa inhibitors

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