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

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

doi:10.1016/j.eclinm.2021.101139

Abstract

BackgroundCoronavirus 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.MethodsWe 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.FindingsOf 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.InterpretationOutpatients 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.FundingNo funding was obtained for this study.

Highlights

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) affects multiple cell types with systemic effects outside the respiratory tract [1,2,3]
To account for patient transfers across hospitals or clinics, data were pooled across different electronic health records (EHRs), and a unique patient identifier was created accounting for the clinic, emergency department, or hospital
Three hundred thirty-one patients were subsequently hospitalized after failing outpatient therapy (5.9%) (Fig. 1)

Summary

Introduction

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) affects multiple cell types with systemic effects outside the respiratory tract [1,2,3]. The binding of SARS-CoV-2 to the target host cell generates the release of inflammatory cytokines, promoting immune cell migration to the site of tissue damage [11] These activated immune cells exacerbate endothelial damage through increased vascular leak and micro thrombus formation [12,13]. The higher mortality rates observed among COVID-19 patients with elevated D-dimers may be related to these mechanisms [7,14,15]. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk.

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Results

Conclusion