Healthcare disparities among anticoagulation therapies for severe COVID-19 patients in the multi-site VIRUS registry

Abstract

Here we analyze hospitalized andintensive care unit coronavirus disease 2019 (COVID-19) patient outcomes from the international VIRUS registry (https://ichgcp.net/clinical-trials-registry/NCT04323787). We find that COVID-19 patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (390 of 1012 = 39%) compared to patients administered enoxaparin but not unfractionated heparin (270 of 1939 = 14%), presenting a risk ratio of 2.79 (95% confidence interval [CI]: [2.42, 3.16]; p = 4.45e-52). This difference persists even after balancing on a number of covariates including demographics, comorbidities, admission diagnoses, and method of oxygenation, with an increased mortality rate on discharge from the hospital of 37% (268 of 733) for unfractionated heparin versus 22% (154 of 711) for enoxaparin, presenting a risk ratio of 1.69 (95% CI: [1.42, 2.00]; p = 1.5e-8). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to patients administered enoxaparin, including acute kidney injury, acute cardiac injury, septic shock, and anemia. Furthermore, a higher percentage of Black/African American COVID patients (414 of 1294 [32%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (671 of 2644 [25%]), risk ratio 1.26 (95% CI: [1.14, 1.40]; p = 7.5e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (311 of 1047 [30%] for Black/African American vs. 263 of 1047 [25%] for White/Caucasian, p = .02, risk ratio 1.18; 95% CI: [1.03, 1.36]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research into the observed racial disparity in anticoagulant use and outcomes for severe COVID-19 patients.

Keywords: biostatistics & bioinformatics; epidemiology; pandemics; social science.

Conflict of interest statement

The authors from nference have financial interests in the company. ADB is a consultant for Abbvie, is on scientific advisory boards for nference and Zentalis, and is founder and President of Splissen therapeutics.

© 2021 The Authors. Journal of Medical Virology Published by Wiley Periodicals LLC.

Figures

Figure 1

Comparison of outcomes between unfractionated heparin and enoxaparin patient cohorts (unadjusted). (A) Bar charts show a comparison of mortality status at discharge from the hospital between patient cohorts receiving enoxaparin but not heparin (blue) or unfractionated heparin but not enoxaparin (orange) during hospitalization. (B) Bar charts show a comparison of mortality status at discharge from the hospital between patient cohorts receiving enoxaparin but not unfractionated heparin (blue) or unfractionated heparin but not enoxaparin (orange) during hospitalization. (C) Histograms show intensive care unit (ICU) Length of Stay in days for cohorts of alive patients who received enoxaparin but not unfractionated heparin (blue) and reported a length of stay in the ICU and alive patients who received unfractionated heparin but not enoxaparin (orange) and reported a length of stay in the ICU. (D) Histograms show hospital Length of Stay in days for cohorts of alive patients who received enoxaparin but not unfractionated heparin (blue) and reported a length of stay in the ICU and alive patients who received unfractionated heparin but not enoxaparin (orange) and reported a length of stay in the hospital. CI, confidence interval

Figure 2

Comparison of outcomes between unfractionated heparin and enoxaparin patient cohorts in patients also reporting comorbidities. Bar charts show a comparison of Mortality Status at discharge from the hospital and status of admission to the ICU for two cohorts—patients receiving enoxaparin and reporting a comorbidity of interest (blue), and patients receiving heparin and reporting a comorbidity of interest (orange). Comorbidities include—hypertension, diabetes, chronic kidney disease and congestive heart failure. Statistics for these plots are included in the corresponding tables. CI, confidence interval; ICU, intemsive care unit