Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization
Tracy Y. Wang, Abdus S. Wahed, Alison Morris, Lisa Baumann Kreuziger, John G. Quigley, Gervasio A. Lamas, Alexandra Weissman, José López‐Sendón, M. Margaret Knudson, Deborah Siegal, Raj S. Kasthuri, Andrew J. Alexander, Lana Wahid, Bassel Atassi, Peter Miller, Janice W. Lawson, Bela Patel, Jerry A. Krishnan, Nancy L. Shapiro, Deborah Martin, Andrei Kindzelski, Eric Leifer, Jungnam Joo, Lingyun Lyu, Annie Pennella, Brendan M. Everett, Mark W. Geraci, Kevin J. Anstrom, Thomas L. Ortel, ACTIV-4C Study Group, Thomas L. Ortel, Tracy Wang, Alison Morris, Lisa Baumann Kreuziger, Steve Wisniewski, Abdus S. Wahed, Kevin J. Anstrom, Eric Leifer, Jerry A. Krishnan, John G. Quigley, Gervasio A. Lamas, Alexandra Weissman, Jose Lopez-Sendon, M. Margaret Knudson, Deborah Siegal, Keith Hoots, Andrei Kindzelski, Renee Leverty, Heather Ann Brown, Guadalupe Andrade, Nita Jain, Franz Feierbach, Karen Serwatkewich, Mary Ann Wolf, Rachel Olson, Annie Pennella, Teresa Atwood, Kelly Lindblom, Ann Schutte, Allegra Stone, Michael A. Morse, Jason E. Lang, Tina Harding, Amanda Harrington, Susan Rogers, Juan Collazo, Nikki Kandray, Meaghan Beauchaine, Jakela Anderson, Danielle Britto, Kimberly Chavis, Tasha Denning, Stephanie García, Angela Pinnix, T. H. WEBB, L. A. Wilson, Vanessa Blumer, Elias Pratt, M. Daugherty, Renee Leverty, A.L. Burnett, Steve Wisniewski, Mark W. Geraci, Johanna Carmel Egan, Emily George, Edvin Music, Alana C Alameida, Jake Schreiber, Frank C. Sciurba, Elyse Perkins, Stephen R. Wisniewski, J.C. Hulbert, Daniel J. Kass, Michael M. Myerburg, Lingyun Lyu, Sophie de Brouwer, Bridget‐Anne Kirwan, Emilie Perrin, Nancy L. Shapiro, Sharon Hasek
Abstract
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.