Edoxaban Vs. Low Molecular Weight Heparin As Anticoagulant Therapy in Hospitalized Patients with Atrial Fibrillation and COVID-19 Infection

Background

During SARS-CoV-2 pandemic, the anticoagulant management in patients with atrial fibrillation (AF) was simplified to the use of low molecular weight heparin (LMWH) in different international guidelines. These recommendations were based for the possible drug interactions between oral anticoagulants and the experimental coronavirus disease 2019 (COVID-19) therapies. However, not all direct oral anticoagulants (DOACs) have the same risk of drug-drug interactions. The metabolism of edoxaban by CYP3A4 is less than 4% being one of the DOACs that poses less of drug-drug interactions risk with the therapy used against the COVID-19 (http://www.covid19-druginteractions.org/). Unfortunately, the current information about the use of DOACs in hospitalized patients with COVID-19 infection is very scarce.

Objective

To determine whether the effectiveness (major thromboembolic events) and safety (bleedings) of edoxaban or low molecular weight heparin (LMWH) were different among patients with AF that had been hospitalized for COVID-19 infection in Catalonia, Spain.

Methods

Observational and multicenter study with a retrospective analysis that consecutively included from March 5th to April 27st 2020 hospitalized patients with the diagnosis of non-valvular AF who received anticoagulant treatment with LMWH or edoxaban concomitantly with the empirical therapy used for COVID-19 infection. The initiation or continuation of anticoagulant treatment with edoxaban was performed according to medical criteria and with close monitoring for possible interactions. The use of LMWH was carried out with therapeutic and intermediate doses. The minimum follow-up was 30 days or until death. Thromboembolic events, hemorrhagic events, length of hospitalization and death from all causes were analyzed. Clinical and analytical factors were compared between both cohorts.

Results

A total of 232 patients (mean age 80.3±7.7 years, 50.0% men, CHA₂DS₂-VASc 4.1±1.4; HAS-BLED 2.6±1.0) were included. Regarding treatment for COVID-19 during hospitalization, the majority of patients were taking azithromycin (98.7%), hydroxychloroquine (89.7%) and ritonavir/lopinavir (81.5%). The biodemographic, analytical characteristics are summarized in the table 1. With regard to outcomes, mean duration of hospitalization was 14.6±7.2 days and mean total time of follow-up (since admission to last visit) was 31.6±13.4 days. 12.9% of patients required admission in the intensive care unit, 18.5% of patients died and 9.9% had a bleeding complication (34.8% major bleeding). Whereas peak mean D-dimer was higher in those patients taking LMWH (1691.7±2240.8 vs 3249.4±5146.3 µg/L; P=0.003). Except for the duration of hospitalization that was longer in those patients taking LMWH (13.3±6.5 vs 16.0±7.7 days; P=0.005), the rest of outcomes similarly occurred in patients treated with edoxaban or LMWH (Table 1).

Conclusions

Approximately one out of 5 hospitalized COVID-19 patients with AF anticoagulated with edoxaban or LMWH died and one out of 10 presented a bleeding complication. Mortality rates, arterial and venous thromboembolic complications and bleedings did not significantly differ between groups. However, the duration of hospitalization was significantly lower with edoxaban. In our clinical practice, edoxaban had a similar therapeutic profile to LMWH and may provide additional benefit. Further studies are needed to determine whether the possible interaction between edoxaban and the antiviral treatment used empirically for COVID-19 is clinically relevant.