Outpatient and Inpatient Anticoagulation Therapy and the Risk for Hospital Admission and Death Among COVID-19 Patients

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

doi:10.2139/ssrn.3734293

Abstract

Background: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state that increases the risk for thrombosis, hospitalization, and mortality. Limited data exist informing the relationship between outpatient anticoagulation therapy 90 days prior to diagnosis and risk for COVID-19 related hospitalization and mortality.Methods: This is a prospective cohort study from March 4th and August 27th, 2020 among 12 hospitals and 60 clinics. We evaluated all patients over the age of 18 diagnosed with COVID-19 for a total of 6,195 consecutive patients.Objectives: We investigated the relationship between 90-day anticoagulation therapy among outpatients prior to COVID-19 diagnosis (OPAC) therapy and the risk for 45 days hospitalization, and mortality as well as the relationship between inpatient prophylactic, escalated prophylactic, or therapeutic anticoagulation (IPAC) therapy and 45 days mortality risk.Results: 598 were immediately hospitalized, and 5,597 were initially treated as outpatients. The case fatality rate was 2.8% (n=175 deaths) and 13% for the overall 45 days mortality and inpatient mortality respectively. Among 5,597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation, and 331 were hospitalized (5.9%). In a multivariable analysis, OPAC 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. In comparison to inpatients who continued anticoagulation therapy upon admission, inpatients who never initiated anticoagulation (before or after hospitalization) realized increased mortality risk, HR (95%CI)=2.26 (1.17, 4.37), p=0.015, while inpatients who initiated anticoagulation upon admission realized no increased risk for mortality HR(95%CI)=1.27(0.75,2.14), p=0.38.Conclusion: Outpatients with COVID-19 using anticoagulation experienced a 43% reduced risk of hospitalization, and initiation of anticoagulation among inpatients was not associated with increased mortality risk.Funding Statement: No specific grant funding was obtained for this study.Declaration of Interests: Dr. Tignanelli is a principal investigator on randomized trials for Covid-19, but not related to anticoagulation. Dr. Haslbauer and Dr. Tzankov received funding support from the Botnar Research Centre for Child Health for all their COVID-19 related research. The remaining authors have nothing to disclose. Ethics Approval Statement: This study was approved by the University of Minnesota’s institutional review board (IRB).

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.

Methods

Results

Conclusion