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      Clinician Trends in Prescribing Direct Oral Anticoagulants for US Medicare Beneficiaries

      research-article
      , MD 1 , , MD, MHS 2 , 3 , 4 , , MD 2 , 5 , , PhD 2 , 5 , , MD, SM 2 , 4 , 5 , , MD, MS 2 , 5 ,
      JAMA Network Open
      American Medical Association

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          Abstract

          This cohort study uses Medicare prescription claims data to evaluate patterns of direct oral anticoagulant prescribing by US clinicians between 2013 and 2018.

          Key Points

          Question

          How have patterns of direct-acting oral anticoagulant (DOAC) use changed among US clinicians between 2013 and 2018?

          Findings

          In this cohort study of Medicare prescription claim data encompassing 325 666 clinicians from 2013 to 2018, most clinicians continued to use warfarin as their predominant or only anticoagulant instead of DOACs, including 1 in 5 general medicine practitioners exclusively using warfarin in 2018. Despite an increase in DOAC prescribing, those prescribing only warfarin in 2013 had lower proportionate DOAC use throughout the study than 2013 DOAC prescribers.

          Meaning

          In this study, many clinicians did not prescribe any DOACs in 2018, suggesting a need to address barriers to DOAC use.

          Abstract

          Importance

          Contemporary national clinical practice guidelines recommend direct-acting oral anticoagulants (DOACs) as the first-line anticoagulant strategy over warfarin for most indications, especially among older individuals with an elevated bleeding risk.

          Objective

          To evaluate anticoagulant prescribing and DOAC uptake by US clinicians in the Medicare population.

          Design, Setting, and Participants

          This retrospective cohort study included all US clinicians with more than 10 Medicare oral anticoagulant prescription claims, who were included in the national Medicare Provider Utilization and Payment Data (2013-2018). Data analyses were conducted between October 2020 and October 2021.

          Exposures

          DOAC prescription in 2013.

          Main Outcomes and Measures

          Clinicians were categorized based on 2013 prescribing as solely prescribing warfarin, DOAC, or both, and their temporal trajectories of proportionate DOAC use were examined.

          Results

          The analysis included 325 666 unique clinicians with more than 10 oral anticoagulant prescriptions between 2013 and 2018 (26 620 [8.2%] cardiologists, 85 563 [26.3%] internal medicine physicians, 84 369 [25.9%] family medicine physicians, and 81 161 [24.9%] advanced practice clinicians, including nurse practitioners and physician assistants). In 2013, among 91 837 prescribers, 54 501 (59.3%) prescribed only warfarin, 1918 (2.1%) prescribed only a DOAC, and 35 418 (38.6%) prescribed both. During the study period, the number of clinicians prescribing DOACs increased, but 19% continued to prescribe only warfarin in 2018. While 359 cardiologists prescribing anticoagulants (1.6%) were warfarin-only prescribers, 10 414 (20.0%) and 6296 (12.6%) of family and internal medicine physicians also prescribed only warfarin, respectively. Clinicians prescribing only warfarin in 2013 had lower proportionate DOAC use throughout the study compared with 2013 DOAC prescribers, which represents a median (IQR) of 41.9% (20.3%-61.9%) of their anticoagulant prescriptions in 2018 vs 67.0% (49.9%-82.8%) for DOAC prescribers.

          Conclusions and Relevance

          Despite the increase in DOAC use among Medicare beneficiaries, many clinicians in this study continued to use warfarin as their predominant or only anticoagulant instead of DOACs. There is a need to address barriers to the uptake of these medications to realize their potential benefits for patients.

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          Most cited references27

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          Fitting Linear Mixed-Effects Models Usinglme4

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            Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.

            The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin. In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism. In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group. In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).
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              Apixaban versus Warfarin in Patients with Atrial Fibrillation

              Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                6 December 2021
                December 2021
                6 December 2021
                : 4
                : 12
                : e2137288
                Affiliations
                [1 ]Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
                [2 ]Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut
                [3 ]Section of General Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
                [4 ]Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut
                [5 ]Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
                Author notes
                Article Information
                Accepted for Publication: October 8, 2021.
                Published: December 6, 2021. doi:10.1001/jamanetworkopen.2021.37288
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Wheelock KM et al. JAMA Network Open.
                Corresponding Author: Rohan Khera, MD, MS, 195 Church St, 5th Flr, New Haven, CT 06510 ( rohan.khera@ 123456yale.edu ).
                Author Contributions : Drs Wheelock and Khera had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Wheelock, Khera.
                Acquisition, analysis, or interpretation of data: All authors.
                Drafting of the manuscript: Wheelock, Khera.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Wheelock, Lin, Khera.
                Administrative, technical, or material support: Khera.
                Supervision: Khera.
                Conflict of Interest Disclosures: Dr Ross reported receiving grants from the US Food and Drug Administration, Johnson and Johnson, Medical Devices Innovation Consortium, Agency for Healthcare Research and Quality, the National Institutes for Health National Heart, Lung, and Blood Institute, and the Laura and John Arnold Foundation outside the submitted work. Dr Lin reported working under contract for the US Centers for Medicare & Medicaid Services. Dr Krumholz reported receiving personal fees from the UnitedHealth, IBM Watson Health, Element Science, Aetna, Facebook, Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin and Baughman Law Firm, F-Prime, the Beijing National Center for Cardiovascular Diseases; being a cofounder of HugoHealth and Refactor Health; receiving grants from the Shenzhen Center for Health Information, Medtronic and the US Food and Drug Administration, Medtronic and Johnson and Johnson, Foundation for a Smoke-Free World, the State of Connecticut Department of Public Health; working with the Centers of Medicare & Medicaid Services; and being a member of the advisory board of Element Science, Facebook, and Aetna outside the submitted work. Dr Khera reported receiving honorarium from the New England Journal of Medicine Journal Watch; being the coinventor of the US Provisional Patent Application No. 63/177,177; and being the founder of Evidence2Health. No other disclosures were reported.
                Funding/Support: Dr Khera was supported by grant K23HL153775 from the National Heart, Lung, and Blood Institute of the National Institutes of Health.
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Article
                zoi211057
                10.1001/jamanetworkopen.2021.37288
                8649845
                34870678
                d6ad5059-b236-4f01-80ba-db58c56de2c4
                Copyright 2021 Wheelock KM et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 5 July 2021
                : 8 October 2021
                Categories
                Research
                Original Investigation
                Online Only
                Pharmacy and Clinical Pharmacology

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