Death Linked to Prior Warfarin Use in Patients Hospitalized With Severe COVID-19

History of warfarin use increases risk for mortality in patients hospitalized with COVID-19.

Increased mortality among patients hospitalized with critical or severe COVID-19 has been associated with prior warfarin use. Chances of major bleeding increase in this population with direct oral anticoagulation (DOAC) use vs no prior anticoagulation, according to study findings published in the International Journal of Cardiology.

Conflicting data for outcomes among patients hospitalized with COVID-19 with prior OAC use led investigators to examine potential risks associated with OAC use prior to hospitalization.

They conducted a retrospective single-center study of 5392 consecutive White, adult patients hospitalized with COVID-19 from March 2020 to June 2021. The majority of patients (median age, 72 years [IQR, 62-81 years]) were diagnosed with critical (15.8%) or severe (70.5%) COVID-19 upon admission according to the World Health Organization definitions. Data were collected through written and electronic medical records. The investigators noted that 9% of patients previously received warfarin therapy, 6.2% of patients previously received DOACs, and 84.8% of patients did not receive prior OACs. During hospitalization, the majority of patients (43.8% women; Charlson comorbidity index [CCI], 4) received low molecular weight heparin thromboprophylaxis and corticosteroids.

During hospitalization, 17.5% of patients required mechanical ventilation support, 22.1% required high-flow oxygen therapy, and 33.7% died. Among all patients, atrial fibrillation was the indication for OAC use in 67.7% of patients on DOACs and in 62.6% of patients receiving warfarin. In 11.6% of patients on DOACs and 11% of patients on warfarin, venous thromboembolism was the indication for OAC use.

Patients who were non-anticoagulated prior to COVID-19 indeed demonstrated features of more pronounced inflammation and activation of coagulation in comparison to anticoagulated patients at the time of hospital admission.

The investigators noted that patients who did not receive anticoagulation therapy had longer duration of symptoms prior to admission, lower CCI, better Eastern Cooperative Oncology Group functional status on admission, and less atrial fibrillation, arterial hypertension, chronic kidney disease, diabetes mellitus, hyperlipoproteinemia, prior venous thromboembolisms, and dementia vs patients with prior anticoagulation with warfarin and DOACs (all P <.05).

Multivariate regression analyses showed prior warfarin use was associated with increased in-hospital death (hazard ratio [HR], 1.24; P =.048) independent of male sex (odds ratio [OR], 1.27; P <.001), higher CCI (OR, 1.26; P <.001), older age (OR, 2.12; P <.001), and severe or critical COVID-19 upon admission (OR, 22.66; P <.001).

Prior DOAC use was associated with higher occurrence of major bleeding (OR, 1.72; P =.045) independent of higher CCI (OR, 1.08; P =.017). The investigators could not accurately evaluate post-admission anticoagulation strategies because the majority of patients received low molecular weight heparin in full therapeutic or prophylactic doses, and additionally because of overlap in anticoagulation strategies.

Study limitations include the retrospective and single-center design, and the inability to discriminate between various DOAC subtypes. Additional limitations include the inability to evaluate post-admission anticoagulation strategies, and lack of generalizability from this high-volume tertiary institution to other clinical contexts.

“…prior warfarin use is associated with increased mortality, whereas DOAC use increases the chances of major bleeding incidents in comparison to no prior anticoagulation among hospitalized COVID-19 patients,” the study authors wrote. “Patients who were nonanticoagulated prior to COVID-19 indeed demonstrated features of more pronounced inflammation and activation of coagulation in comparison to anticoagulated patients at the time of hospital admission.”

This article originally appeared on The Cardiology Advisor


Bistrovic P, Sabljic A, Kovacevic I, et al. Risks associated with prior oral anticoagulation use in hospitalized COVID-19 patients – a retrospective cohort study on 5392 patients from a tertiary centre. Int J Cardiol. Published online November 26, 2022. doi:10.1016/j.ijcard.2022.11.051