Enoxaparin is associated with lower rates of mortality than unfractionated Heparin in hospitalized COVID-19 patients.

BACKGROUND: Coagulopathies are a major class among COVID-19 associated complications. Although anticoagulants such as unfractionated Heparin and Enoxaparin are both being used for therapeutic mitigation of COVID associated coagulopathy (CAC), differences in their clinical outcomes remain to be investigated. METHODS: We analyzed records of 1,113 patients in the Mayo Clinic Electronic Health Record (EHR) database who were admitted to the hospital for COVID-19 between April 4, 2020 and August 31, 2020, including 19 different Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin. Among this patient population, we compared cohorts of patients who received different types of anticoagulants, including 441 patients who received unfractionated Heparin and 166 patients who received Enoxaparin. Clinical outcomes at 28 days were compared, and propensity score matching was used to control for potential confounding variables including: demographics, comorbidities, ICU status, chronic kidney disease stage, and oxygenation status. Patients with a history of acute kidney injury and patients who received multiple types of anticoagulants were excluded from the study. FINDINGS: We find that COVID-19 patients administered unfractionated Heparin but not Enoxaparin have higher rates of 28-day mortality (risk ratio: 4.3; 95% Confidence Interval [C.I.].: [1.8, 10.2]; p-value: 8.5e-4, Benjamini Hochberg [BH] adjusted p-value: 2.1e-3), after controlling for potential confounding factors. INTERPRETATION: This study emphasizes the need for mechanistically investigating differential modulation of the COVID-associated coagulation cascades by Enoxaparin versus unfractionated Heparin. FUNDING: This work was supported by Nference, inc.

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

Here we analyze hospitalized andintensive care unit coronavirus disease 2019 (COVID-19) patient outcomes from the international VIRUS registry (https://clinicaltrials.gov/ct2/show/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.