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      Comparative Safety and Effectiveness of Direct Oral Anticoagulants and Warfarin during Chemotherapy in Cancer Patients with Venous Thromboembolism Aged 75 Years or Older: A Nationwide Inpatient Database Study

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          Abstract

          Introduction

          Venous thromboembolism (VTE) is a life-threatening complication occurring in cancer patients. Direct oral anticoagulants (DOACs) or warfarin are widely prescribed for treating cancer-associated VTE. However, data are sparse as to the effectiveness and bleeding complications associated with these medications in elderly patients. The purpose of this study was to compare effectiveness and safety profiles between DOACs and warfarin in elderly cancer patients undergoing chemotherapy.

          Methods

          Using the Diagnosis Procedure Combination inpatient database, we retrospectively identified cancer patients aged ≥75 years who developed VTE during chemotherapy ( n = 4,278, January 2016 to March 2020). Eligible patients were divided into those receiving warfarin ( n = 557) and DOACs ( n = 3,721). We conducted a 1:4 propensity score matching analysis to adjust for measured confounders. The primary outcome was VTE recurrence requiring hospitalization. Secondary outcomes were major bleeding requiring hospitalization and inhospital death from all causes within 6 months.

          Results

          The propensity-matched cohort included 557 patients in the warfarin group and 2,278 patients in the DOACs group. The proportion of VTE recurrence requiring hospitalization was lower in the DOACs group (5.3% vs. 7.5%; odds ratio [OR], 0.69; 95% confidence interval [CI], 0.48–0.98). The proportion of recurrent deep vein thrombosis was 6.3% and 4.4%, while that of recurrent pulmonary emboli was 1.3% and 1.3% in the warfarin and DOACs groups, respectively. No statistically significant differences were found in the proportion of major bleeding events requiring hospitalization (1.6% vs. 1.1%; OR, 1.47; 95% CI, 0.62–3.50) or all-cause inhospital mortality (11.1% vs. 9.9%; OR, 1.14; 95% CI, 0.84–1.56) between the DOACs and warfarin groups.

          Conclusion

          Our findings suggest that DOACs may be more effective than warfarin in terms of VTE recurrence requiring hospitalization and that these medications may be equivalent in terms of safety.

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          Most cited references34

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          An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies

          The propensity score is the probability of treatment assignment conditional on observed baseline characteristics. The propensity score allows one to design and analyze an observational (nonrandomized) study so that it mimics some of the particular characteristics of a randomized controlled trial. In particular, the propensity score is a balancing score: conditional on the propensity score, the distribution of observed baseline covariates will be similar between treated and untreated subjects. I describe 4 different propensity score methods: matching on the propensity score, stratification on the propensity score, inverse probability of treatment weighting using the propensity score, and covariate adjustment using the propensity score. I describe balance diagnostics for examining whether the propensity score model has been adequately specified. Furthermore, I discuss differences between regression-based methods and propensity score-based methods for the analysis of observational data. I describe different causal average treatment effects and their relationship with propensity score analyses.
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            Using the Standardized Difference to Compare the Prevalence of a Binary Variable Between Two Groups in Observational Research

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              Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update

              PURPOSE To provide updated recommendations about prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer. METHODS PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs published from August 1, 2014, through December 4, 2018. ASCO convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS The systematic review included 35 publications on VTE prophylaxis and treatment and 18 publications on VTE risk assessment. Two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in patients with cancer reported that edoxaban and rivaroxaban are effective but are linked with a higher risk of bleeding compared with low-molecular-weight heparin (LMWH) in patients with GI and potentially genitourinary cancers. Two additional RCTs reported on DOACs for thromboprophylaxis in ambulatory patients with cancer at increased risk of VTE. RECOMMENDATIONS Changes to previous recommendations: Clinicians may offer thromboprophylaxis with apixaban, rivaroxaban, or LMWH to selected high-risk outpatients with cancer; rivaroxaban and edoxaban have been added as options for VTE treatment; patients with brain metastases are now addressed in the VTE treatment section; and the recommendation regarding long-term postoperative LMWH has been expanded. Re-affirmed recommendations: Most hospitalized patients with cancer and an acute medical condition require thromboprophylaxis throughout hospitalization. Thromboprophylaxis is not routinely recommended for all outpatients with cancer. Patients undergoing major cancer surgery should receive prophylaxis starting before surgery and continuing for at least 7 to 10 days. Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE. Additional information is available at www.asco.org/supportive-care-guidelines .
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                Author and article information

                Journal
                Gerontology
                Gerontology
                GER
                Gerontology
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                0304-324X
                1423-0003
                May 2023
                9 December 2022
                9 December 2022
                : 69
                : 5
                : 561-570
                Affiliations
                [1] aDepartment of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan
                [2] bDepartment of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
                [3] cDepartment of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
                [4] dDepartment of Breast and Endocrine Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
                [5] eCenter for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
                [6] fDepartment of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
                Author notes
                *Chikako Iwai,
                Article
                ger-0069-0561
                10.1159/000528606
                10332483
                36502790
                23441edb-50ce-4057-8193-235a30a70d47
                Copyright © 2022 by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission.

                History
                : 29 June 2022
                : 2 December 2022
                : 2023
                Page count
                Figures: 1, Tables: 3, References: 34, Pages: 10
                Funding
                This work was supported by grants from the Ministry of Health, Labour and Welfare, Japan (21AA2007 and 22AA2003), and the Ministry of Education, Culture, Sports, Science and Technology, Japan (20H03907).
                Categories
                Clinical Section: Research Article

                old age,chemotherapy,direct oral anticoagulants,venous thromboembolism,warfarin

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