Extended Thromboprophylaxis in Patients Hospitalized with COVID-19 at Time of Discharge is Not Associated with Improvement in Quality of Life

Am J Med. 2025 Oct;138(10):1464-1468.e1. doi: 10.1016/j.amjmed.2025.06.003. Epub 2025 Jun 11.

Abstract

Background: The long-term effects of COVID-19, known as post-acute sequelae of SARS-CoV-2 infection (PASC), impair quality of life (QoL). This secondary analysis of the ACTIV-4c clinical trial evaluates the specific effects of extended thromboprophylaxis with apixaban on individual QoL domains, assessed by EQ-5D-5L index, in patients discharged after COVID-19 hospitalization.

Methods: ACTIV-4c study was a prospective randomized, placebo-controlled, double-blind clinical trial. We enrolled 1,217 patients hospitalized with COVID-19 at 107 U.S. hospitals between February 2021 and June 2022. Participants were randomized to apixaban 2.5 mg twice daily or placebo for 30 days post-discharge. QoL was assessed using EQ-5D-5L index at 2, 30, and 90 days post-discharge, evaluating five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Data were analyzed using chi-square tests and proportional odds models adjusted for multiple variables.

Results: Of 1,217 participants, 610 received apixaban and 607 received placebo. By 2 days post-discharge, 43.5% of apixaban and 45.0% of placebo recipients reported moderate impairment in one or more EQ-5D-5L domains, particularly usual activities (33.0%). At 30 days, moderate impairment persisted in 30.8% of apixaban and 33.4% of placebo recipients, improving most in the usual activities domain (17.4%). At 90 days, 31.5% of apixaban and 28.5% of placebo recipients reported moderate impairment. Extended thromboprophylaxis with apixaban was not associated with significant improvements in any EQ-5D-5L domains at 30 or 90 days.

Conclusions: Extended thromboprophylaxis with apixaban after COVID-19 hospitalization does not improve QoL. The high prevalence of QoL impairment highlights the need for targeted interventions for PASC.

Keywords: Anticoagulants; COVID-19; PASC; Quality of life; Thromboembolism.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • COVID-19* / complications
  • Double-Blind Method
  • Factor Xa Inhibitors* / administration & dosage
  • Factor Xa Inhibitors* / therapeutic use
  • Female
  • Hospitalization
  • Humans
  • Male
  • Middle Aged
  • Patient Discharge
  • Prospective Studies
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / therapeutic use
  • Pyridones* / administration & dosage
  • Pyridones* / therapeutic use
  • Quality of Life*
  • SARS-CoV-2
  • Venous Thromboembolism* / prevention & control

Substances

  • apixaban
  • Pyrazoles
  • Pyridones
  • Factor Xa Inhibitors