High risk subgroups were not identified to benefit from thromboprophylaxis after hospitalization for COVID-19

Background The Accelerating Coronavirus 2019 (COVID-19) Therapeutic Interventions and Vaccines (ACTIV)-4c trial investigated prophylactic apixaban for 30 days following hospitalization with COVID-19. The overall incidence of early post-discharge death or thromboembolism was low, and the trial was closed early. Aims To identify a high-risk patient population who might benefit from post-discharge thromboprophylaxis through subgroup analyses stratified by age, race/ethnicity, obesity, D-dimer elevation, WHO Score, and modified IMPROVE-VTE score on 30-day composite outcome of all-cause death, arterial thromboembolism (ATE), and venous thromboembolism (VTE). Methods Cumulative incidence of all-cause death, ATE, and VTE within 30 days were described for each subgroup. Time to death, ATE, or VTE by 30 days were analyzed using Cox proportional hazard models with interaction testing for each subgroup. Results Among 1217 patients randomized to apixaban or placebo, 32% were >60 years old. Modified IMPROVE VTE score was ≥4 in 2% and was 2-3 with an elevated D-dimer in an additional 9% of participants. The overall incidence of the primary endpoint was 2.13% in the apixaban group and 2.31% in the placebo group. At Day 30, similar rates of the primary endpoint occurred within subgroups except for participants >60 years. No benefit of thromboprophylaxis was seen in any subgroup. Conclusion The combined incidence of 30-day death, ATE, and VTE was low in patients who survived COVID hospitalization, except in patients over age 60. Due to the limited number of events, the findings remain inconclusive; nonetheless, the study did not identify a high-risk subgroup that would derive benefits from extended thromboprophylaxis.