Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization
Creators: name: Lopez-Sendon, Jose
name: Kreuziger, Lisa Baumann
name: Pennella, Annie
name: Shapiro, Nancy L.
name: Weissman, Alexandra J.
name: Siegal, Deborah M.
name: ACTIV-4C Study Group
name: Lamas, Gervasio A.
name: Ortel, Thomas L.
name: Knudson, M. Margaret
name: Alexander, Andrew J.
name: Lyu, Lingyun
name: Kasthuri, Raj S.
name: Wang, Tracy Y.
name: Atassi, Bassel
name: Kindzelski, Andrei L.
name: Geraci, Mark W.
name: Leifer, Eric S.
name: Wahid, Lana
name: Morris, Alison
name: Lawson, Janice W.
name: Everett, Brendan M.
name: Anstrom, Kevin J.
name: Joo, Jungnam
name: Patel, Bela
name: Wahed, Abdus S.
name: Miller, Peter J.
name: Quigley, John G.
name: Martin, Deborah E.
name: Krishnan, Jerry A.
Publisher: name: American College of Physicians
Year: 2023

description: <p>BACKGROUND: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear. OBJECTIVE: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087). SETTING: Done during 2021 to 2022 among 127 U.S. hospitals. PARTICIPANTS: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation. INTERVENTION: 2.5 mg of apixaban versus placebo twice daily for 30 days. MEASUREMENTS: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding. RESULTS: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment. LIMITATIONS: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity. CONCLUSION: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive. PRIMARY FUNDING SOURCE: National Institutes of Health.</p>