Availability of Specific Direct Oral Anticoagulant Reversal Agents in US Hospitals | Cardiology | JAMA Network Open | JAMA Network
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Figure.  Reversal Agent Availability by State
Reversal Agent Availability by State
Table.  Hospitals With Idarucizumab and Andexanet Alfa
Hospitals With Idarucizumab and Andexanet Alfa
1.
Tomaselli  GF, Mahaffey  KW, Cuker  A,  et al.  2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Solution Set Oversight Committee.   J Am Coll Cardiol. 2020;76(5):594-622. doi:10.1016/j.jacc.2020.04.053PubMedGoogle ScholarCrossref
2.
Lip  GYH, Banerjee  A, Boriani  G,  et al.  Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report.   Chest. 2018;154(5):1121-1201. doi:10.1016/j.chest.2018.07.040PubMedGoogle ScholarCrossref
3.
Cuker  A, Burnett  A, Triller  D,  et al.  Reversal of direct oral anticoagulants: guidance from the Anticoagulation Forum.   Am J Hematol. 2019;94(6):697-709. doi:10.1002/ajh.25475PubMedGoogle ScholarCrossref
4.
Witt  DM, Nieuwlaat  R, Clark  NP,  et al.  American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy.   Blood Adv. 2018;2(22):3257-3291. doi:10.1182/bloodadvances.2018024893PubMedGoogle ScholarCrossref
5.
Zhu  J, Alexander  GC, Nazarian  S, Segal  JB, Wu  AW.  Trends and variation in oral anticoagulant choice in patients with atrial fibrillation, 2010-2017.   Pharmacotherapy. 2018;38(9):907-920. doi:10.1002/phar.2158PubMedGoogle ScholarCrossref
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    Research Letter
    Cardiology
    May 14, 2021

    Availability of Specific Direct Oral Anticoagulant Reversal Agents in US Hospitals

    Author Affiliations
    • 1Division of General Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
    • 2Department of Medicine, Harvard Medical School, Boston, Massachusetts
    • 3Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, Massachusetts
    • 4Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center, Boston, Massachusetts
    JAMA Netw Open. 2021;4(5):e2110079. doi:10.1001/jamanetworkopen.2021.10079
    Introduction

    Direct oral anticoagulants (DOACs) are widely prescribed but associated with risk of major hemorrhage. Specific reversal agents have been developed for dabigatran (idarucizumab) and factor Xa inhibitors (andexanet alfa). Consensus statements from several1-3 but not all4 major organizations recommend these specific reversal agents, if available, over alternatives, such as prothrombin complex concentrates (PCC), in DOAC-associated life-threatening bleeding. Given the importance of timely reversal in life-threatening hemorrhage, we assessed the availability of specific DOAC reversal agents in US hospitals.

    Methods

    This cross-sectional study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline and was deemed non–human participant research and exempt from review by the Beth Israel Deaconess Medical Center Committee on Clinical Investigation. We used the Medicare Hospital Compare database to find eligible hospitals in the United States that provide emergency care, excluding those in territories, those operated by the Department of Defense, and those primarily designated as pediatric or psychiatric facilities. We searched each included hospital on pharmaceutical company drug locator websites for idarucizumab and andexanet alfa to assess whether they did or did not have access to each drug. Searches were conducted on manufacturer websites between March 11, 2020, and November 11, 2020, and analyzed from March 11, 2020, to February 15, 2021. Per the websites, the idarucizumab database was accurate as of May 31, 2019, and the andexanet alfa database was accurate as of March 31, 2020. Eligible hospitals were categorized as trauma centers if they were designated level 1 or 2 by the American Trauma Society. Information about our data sources can be found in the eMethods in the Supplement.

    We provide descriptive statistics. We used χ2 tests to assess the association between hospital attributes (ie, hospital type, trauma status, state) and access to idarucizumab and, separately, andexanet alfa. All analyses were performed with Stata version 13 (StataCorp). Maps were completed using the spmap and maptile commands. Statistical significance was set at P < .05, and all tests were 2-tailed.

    Results

    There were 5340 hospitals in the Medicare Compare database. Of these, 4276 (80.1%) met inclusion criteria (Table). Among these hospitals, 2562 (59.9%) had idarucizumab, and 499 (11.7%) had andexanet alfa. Availability of medications varied by hospital type for both idarucizumab (χ2 = 831.8; P < .001) and andexanet alfa (χ2 = 139.6; P < .001). Among 528 trauma centers, 503 (95.3%) had idarucizumab, and 151 (28.6%) had andexanet alfa. The proportion of hospitals with access to idarucizumab (range, 22%-100%; χ2 = 576.7; P < .001) and andexanet alfa (range, 0%-50%; χ2 = 249.9; P < .001) varied by state (Figure).

    Discussion

    In our study of 4276 US hospitals providing emergency care, we found a significant discrepancy in the availability of andexanet alfa and idarucizumab. Despite factor Xa inhibitors being prescribed for atrial fibrillation 20 times more frequently than dabigatran,5 acute care hospitals and trauma centers were 5 times and 3 times less likely, respectively, to have access to andexanet alfa than idarucizumab. The availability of each medication varied substantially across states and regions. To our knowledge, this is the first assessment of national availability of DOAC reversal agents.

    Limitations of this study include the use of nonvalidated industry data related to medication purchases rather than confirmation of stock on hand, which could potentially overestimate availability if stock is exhausted and not replenished. Second, company data were slightly out of date and from different time periods, but we do not anticipate that these factors affected the overall results. Third, idarucizumab was approved by the US Food and Drug Administration in October 2015, while andexanet alfa was approved in May 2018. However, we saw negligible increases in andexanet alfa availability between December 2019 and March 2020 (data not shown), so we do not think this is a significant limitation. Fourth, we did not assess the availability of 4-factor PCC, which some hospitals may have chosen to stock rather than andexanet alfa.

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    Article Information

    Accepted for Publication: March 22, 2021.

    Published: May 14, 2021. doi:10.1001/jamanetworkopen.2021.10079

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Kanjee Z et al. JAMA Network Open.

    Corresponding Author: Zahir Kanjee MD, MPH, Division of General Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Hospital Medicine Office, Span 2, Boston MA 02115 (zkanjee@bidmc.harvard.edu).

    Author Contributions: Drs Kanjee and McCann had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Kanjee, Freed.

    Acquisition, analysis, or interpretation of data: Kanjee, McCann.

    Drafting of the manuscript: Kanjee, Freed.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Kanjee.

    Supervision: Freed.

    Conflict of Interest Disclosures: Dr Kanjee reported serving as a member of a paid advisory board on medical education products for Wolters Kluwer; receiving royalties from Wolters Kluwer for books he has edited; receiving personal fees for continuing medical education from Oakstone Publishing; and serving as an assistant series editor for Annals of Internal Medicine. No other disclosures were reported.

    Additional Contributions: We are grateful to Shoshana Herzig, MD, MPH (Beth Israel Deaconess Medical Center; Harvard Medical School), Devraj Sukul, MD, MSc (University of Michigan), and Sebastien Haneuse, PhD (Harvard School of Public Health; JAMA Network Open), for technical assistance with statistical analysis and the anonymous journal reviewers for helpful suggestions. None of these individuals were compensated for their time.

    References
    1.
    Tomaselli  GF, Mahaffey  KW, Cuker  A,  et al.  2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Solution Set Oversight Committee.   J Am Coll Cardiol. 2020;76(5):594-622. doi:10.1016/j.jacc.2020.04.053PubMedGoogle ScholarCrossref
    2.
    Lip  GYH, Banerjee  A, Boriani  G,  et al.  Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report.   Chest. 2018;154(5):1121-1201. doi:10.1016/j.chest.2018.07.040PubMedGoogle ScholarCrossref
    3.
    Cuker  A, Burnett  A, Triller  D,  et al.  Reversal of direct oral anticoagulants: guidance from the Anticoagulation Forum.   Am J Hematol. 2019;94(6):697-709. doi:10.1002/ajh.25475PubMedGoogle ScholarCrossref
    4.
    Witt  DM, Nieuwlaat  R, Clark  NP,  et al.  American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy.   Blood Adv. 2018;2(22):3257-3291. doi:10.1182/bloodadvances.2018024893PubMedGoogle ScholarCrossref
    5.
    Zhu  J, Alexander  GC, Nazarian  S, Segal  JB, Wu  AW.  Trends and variation in oral anticoagulant choice in patients with atrial fibrillation, 2010-2017.   Pharmacotherapy. 2018;38(9):907-920. doi:10.1002/phar.2158PubMedGoogle ScholarCrossref
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