Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients

Sameh M Hozayen; Diana Zychowski; Sydney Benson; Pamela L Lutsey; Jasmin Haslbauer; Alexandar Tzankov; Zachary Kaltenborn; Michael Usher; Surbhi Shah; Christopher J Tignanelli; Ryan T Demmer

doi:10.1016/j.eclinm.2021.101139

Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients

EClinicalMedicine. 2021 Nov:41:101139. doi: 10.1016/j.eclinm.2021.101139. Epub 2021 Sep 24.

Authors

Affiliations

¹ Department of Medicine, Division of General Internal Medicine, Assistant Professor of Medicine, Hospitalist, University of Minnesota, Mayo Building, 420 Delaware Street, SE, 6 Floor, Room D694, Minneapolis, MN 55455, United States.
² Department of Medical Education, University of Minnesota, United States.
³ Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States.
⁴ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States.
⁵ Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Switzerland.
⁶ Department of Hematology and oncology, Mayo Clinic, Arizona, United States.
⁷ Department of Surgery, University of Minnesota, Minneapolis, MN, United States.
⁸ Institute for Health Informatics, University of Minnesota, Minneapolis, MN, United States.
⁹ Department of Surgery, North Memorial Health Hospital, Robbinsdale, MN, United States.
¹⁰ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States.

Abstract

Background: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality.

Methods: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk.

Findings: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015.

Interpretation: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk.

Funding: No funding was obtained for this study.

Keywords: %, percentage; (n), number; ACEi, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers; Anticoagulation; CI, confidence intervals; CKD, chronic kidney disease; CO2, carbon dioxide; COPD, chronic obstructive pulmonary disease; COVID-19; COVID-19, coronavirus disease 2019; D-dimer; DIC, disseminated intravascular coagulation; DOAC, direct oral anticoagulant; EHR, electronic health records; EMR, electronic medical records; HCT, hematocrit; HIT, heparin-induced thrombocytopenia; HR, hazard ratio; Hospitalization; IPAC, inpatient anticoagulation therapy; IRB, institutional review board; Inpatient; MI, prior myocardial infarction; Mortality; OPAC, outpatient persistent anticoagulation therapy; Outpatient; RDW, red blood cell distribution width; SARS-CoV-2, severe Acute Respiratory Syndrome Coronavirus-2; SBP, systolic blood pressure; SBP-min, minimum systolic blood pressure; SD, standard deviations; SE, standard errors; SpO2-min, minimum oxygen saturation; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; VTE, venous thromboembolism; WBC, white blood cell; mg/dl, milligram per deciliter; rt-PCR, reverse transcriptase-polymerase chain reaction.

Grants and funding

R01 HS026732/HS/AHRQ HHS/United States