What is the frequency with which patients hospitalized with COVID-19 are treated with venous thromboembolism (VTE) prophylactic- and treatment-dose anticoagulation, and what is the association of anticoagulation with in-hospital and 60-day mortality?
In this cohort study of 1351 patients hospitalized with COVID-19 in which 1127 patients received anticoagulation, 34.8% missed 2 or more days of VTE prophylaxis. Use of only prophylactic-dose or treatment-dose anticoagulation was associated with lower in-hospital mortality vs no anticoagulation; however, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days.
These findings suggest that prophylactic-dose VTE anticoagulation may be optimal therapy for patients hospitalized with COVID-19.
Venous thromboembolism (VTE) is a common complication of COVID-19. It is not well understood how hospitals have managed VTE prevention and the effect of prevention strategies on mortality.
To characterize frequency, variation across hospitals, and change over time in VTE prophylaxis and treatment-dose anticoagulation in patients hospitalized for COVID-19, as well as the association of anticoagulation strategies with in-hospital and 60-day mortality.
Design, Setting, and Participants
This cohort study of adults hospitalized with COVID-19 used a pseudorandom sample from 30 US hospitals in the state of Michigan participating in a collaborative quality initiative. Data analyzed were from patients hospitalized between March 7, 2020, and June 17, 2020. Data were analyzed through March 2021.
Nonadherence to VTE prophylaxis (defined as missing ≥2 days of VTE prophylaxis) and receipt of treatment-dose or prophylactic-dose anticoagulants vs no anticoagulation during hospitalization.
Main Outcomes and Measures
The effect of nonadherence and anticoagulation strategies on in-hospital and 60-day mortality was assessed using multinomial logit models with inverse probability of treatment weighting.
Of a total 1351 patients with COVID-19 included (median [IQR] age, 64 [52-75] years; 47.7% women, 48.9% Black patients), only 18 (1.3%) had a confirmed VTE, and 219 (16.2%) received treatment-dose anticoagulation. Use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased over time (adjusted odds ratio [aOR], 1.46; 95% CI, 1.31-1.61 per week). Of 1127 patients who ever received anticoagulation, 392 (34.8%) missed 2 or more days of prophylaxis. Missed prophylaxis varied from 11% to 61% across hospitals and decreased markedly over time (aOR, 0.89; 95% CI, 0.82-0.97 per week). VTE nonadherence was associated with higher 60-day (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.03-1.67) but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03). Receiving any dose of anticoagulation (vs no anticoagulation) was associated with lower in-hospital mortality (only prophylactic dose: aHR, 0.36; 95% CI, 0.26-0.52; any treatment dose: aHR, 0.38; 95% CI, 0.25-0.58). However, only the prophylactic dose of anticoagulation remained associated with lower mortality at 60 days (prophylactic dose: aHR, 0.71; 95% CI, 0.51-0.90; treatment dose: aHR, 0.92; 95% CI, 0.63-1.35).
Conclusions and Relevance
This large, multicenter cohort of patients hospitalized with COVID-19, found evidence of rapid dissemination and implementation of anticoagulation strategies, including use of treatment-dose anticoagulation. As only prophylactic-dose anticoagulation was associated with lower 60-day mortality, prophylactic dosing strategies may be optimal for patients hospitalized with COVID-19.
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Accepted for Publication: April 3, 2021.
Published: June 11, 2021. doi:10.1001/jamanetworkopen.2021.11788
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Vaughn VM et al. JAMA Network Open.
Corresponding Author: Valerie M. Vaughn, MD, MSc, Assistant Professor of Medicine, Division of General Internal Medicine, University of Utah, 30 N 1900 E, Room 5R218, Salt Lake City, UT 84132 (firstname.lastname@example.org).
Author Contributions: Mss. Yost and Abshire 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: Vaughn, Kim, Barnes.
Acquisition, analysis, or interpretation of data: Vaughn, Yost, Abshire, Flanders, Paje, Grant, Kaatz, Barnes.
Drafting of the manuscript: Vaughn, Yost, Abshire, Paje, Barnes.
Critical revision of the manuscript for important intellectual content: Abshire, Flanders, Paje, Grant, Kaatz, Kim.
Statistical analysis: Vaughn, Yost, Abshire.
Administrative, technical, or material support: Vaughn, Flanders, Kim.
Supervision: Grant, Barnes.
Conflict of Interest Disclosures: Dr Vaughn reported receiving speaking fees from Thermo Fisher Scientific. Dr Yost reported receiving salary support from Blue Cross Blue Shield of Michigan for work with the Michigan Value Collaborative. Dr Flanders reported receiving grants from Blue Cross Blue Shield of Michigan outside the submitted work. Dr Kaatz reported receiving grants from Janssen Pharmaceuticals, Bristol Myers Squibb, and Osmosis Research; he reported receiving consulting fees from Janssen Pharmaceuticals, Bristol Myers Squibb, Pfizer, Alexion Pharmaceuticals, and CSL Behring during the conduct of the study, and consulting fees from Norvartis outside the submitted work. Dr Barnes reported receiving consulting fees from Pfizer/Bristol-Myers Squibb, Janssen Pharmaceuticals, AMAG Pharmaceuticals, Acelis Connected Health, and grants from Blue Cross Blue Shield of Michigan during the conduct of the study. No other disclosures were reported.
Funding/Support: This work was supported by Blue Cross and Blue Shield of Michigan and Blue Care Network as part of their Value Partnerships program. Dr Vaughn is supported by a career development award from the Agency for Healthcare Research and Quality (grant No. 1-K08-HS26530-01). Dr Barnes is supported by the National Heart, Lung, and Blood Institute (grant No. K01 HL135392) and by Blue Cross and Blue Shield of Michigan.
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.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality, National Heart, Lung, and Blood Institute, or Blue Cross and Blue Shield of Michigan.
Additional Contributions: We would like to acknowledge all participating CQIs and their members. Participating CQIs include: Hospital Medicine Safety (HMS) Consortium, Michigan Anticoagulation Quality Improvement Initiative (MAQI2), Michigan Value Collaborative (MVC), Michigan Bariatric Surgery Collaborative (MBSC), Michigan Surgical Quality Collaborative (MSQC), Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI), Michigan Emergency Department Improvement Collaborative (MEDIC), Michigan Radiation Oncology Quality Collaborative (MROQC), Michigan Spine Surgery Improvement Collaborative (MSSIC), Integrated Michigan Patient-Centered Alliance in Care Transitions (IMPACT), and Michigan Trauma Quality Improvement Program (MTQIP).
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