• Tracy Y Wang, Abdus S Wahed, Alison Morris, Lisa Baumann Kreuziger, John G Quigley, Gervasio A Lamas, Alexandra J Weissman, Jose Lopez-Sendon, M Margaret Knudson, Deborah M Siegal, Raj S Kasthuri, Andrew J Alexander, Lana Wahid, Bassel Atassi, Peter J Miller, Janice W Lawson, Bela Patel, Jerry A Krishnan, Nancy L Shapiro, Deborah E Martin, Andrei L Kindzelski, Eric S Leifer, Jungnam Joo, Lingyun Lyu, Annie Pennella, Brendan M Everett, Mark W Geraci, Kevin J Anstrom, Thomas L Ortel, and ACTIV-4C Study Group.
• Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina (T.Y.W., A.P.).
• Ann. Intern. Med. 2023 Apr 1; 176 (4): 515523515-523.

BackgroundPatients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear.ObjectiveTo determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization.DesignProspective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087).SettingDone during 2021 to 2022 among 127 U.S. hospitals.ParticipantsAdults 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.Intervention2.5 mg of apixaban versus placebo twice daily for 30 days.MeasurementsThe 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.ResultsEnrollment 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.LimitationsThe 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.ConclusionThe 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 SourceNational Institutes of Health.

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