TY - JOUR
T1 - Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization
AU - ACTIV-4C Study Group
AU - Wang, Tracy Y.
AU - Wahed, Abdus S.
AU - Morris, Alison
AU - Kreuziger, Lisa Baumann
AU - Quigley, John G.
AU - Lamas, Gervasio A.
AU - Weissman, Alexandra J.
AU - Lopez-Sendon, Jose
AU - Knudson, M. Margaret
AU - Siegal, Deborah M.
AU - Kasthuri, Raj S.
AU - Alexander, Andrew J.
AU - Wahid, Lana
AU - Atassi, Bassel
AU - Miller, Peter J.
AU - Lawson, Janice W.
AU - Patel, Bela
AU - Krishnan, Jerry A.
AU - Shapiro, Nancy L.
AU - Martin, Deborah E.
AU - Kindzelski, Andrei L.
AU - Leifer, Eric S.
AU - Joo, Jungnam
AU - Lyu, Lingyun
AU - Pennella, Annie
AU - Everett, Brendan M.
AU - Geraci, Mark W.
AU - Anstrom, Kevin J.
AU - Ortel, Thomas L.
AU - Wisniewski, Steve
AU - Hoots, Keith
AU - Leverty, Renee
AU - Brown, Heather Ann
AU - Andrade, Guadalupe
AU - Jain, Nita
AU - Feierbach, Franz
AU - Serwatkewich, Karen
AU - Wolf, Mary Ann
AU - Olson, Rachel
AU - Atwood, Teresa
AU - Lindblom, Kelly
AU - Schutte, Ann
AU - Stone, Allegra
AU - Morse, Michael
AU - Lang, Jason
AU - Harding, Tina
AU - Harrington, Amanda
AU - Rogers, Susan
AU - Collazo, Juan
AU - Kandray, Nikki
AU - Beauchaine, Meaghan
AU - Anderson, Jakela
AU - Britto, Danielle
AU - Chavis, Kimberly
AU - Denning, Tasha
AU - Garcia, Stephanie
AU - Pinnix, Angela
AU - Webb, Tashyia
AU - Wilson, Labriah
AU - Blumer, Vanessa
AU - Pratt, Elias
AU - Daugherty, Molly
AU - Burnett, Ann
AU - Wisniewski, Steve
AU - Egan, Johanna Carmel
AU - George, Emily
AU - Music, Edvin
AU - Alameida, Alana
AU - Schreiber, Jake
AU - Sciurba, Frank
AU - Perkins, Elyse
AU - Wisniewski, Stephen
AU - Hulbert, Joshua
AU - Kass, Daniel
AU - Myerburg, Michael M.
AU - Brouwer, Sophie de
AU - Kirwan, Bridget Anne
AU - Perrin, Emilie
AU - Hasek, Sharon
AU - Predki, Barbara
AU - Martinez, Miriam
AU - Barbera, Sunni
AU - Sculley, Jennifer
AU - Peterson, Jennifer
AU - Illendula, Sai
AU - DeLisa, Julie
AU - Castro, Lauren
AU - Huynh, Nina
AU - Uppuluri, Ellen
AU - Lee, James
AU - Speakman, Lauren
AU - Idrees, Niha
AU - Mei, Conny
AU - Pozzolano, Erin
AU - Driscoll, Tara
AU - Skific, Damir
AU - Collins, Joseph
AU - Hanna, Aletha
AU - Mersc, Sheri
AU - Simtion, Sorina
AU - Hegde, Sheila
AU - Kim, Yuri
AU - Galanaud, Jean Philippe
AU - Le Gal, Gregoire
AU - Rost, Natalia
AU - van Diepen, Sean
AU - Singhal, Aneesh
AU - Becker, Richard C.
AU - del Zoppo, Gregory
AU - Glynn, Robert
AU - Henke, Peter
AU - Holubkov, Richard
AU - Kerr, Kim
AU - Lee, Agnes
AU - Lipman, Hannah
AU - Lure, Fedor
AU - Vesely, Sara
AU - Wenner, Danielle
AU - Hoots, Keith
AU - Punturieri, Antonello
AU - Sakovich, Ben
AU - Snyder, Jeff
AU - Milliken, D. J.
AU - Bucheimer, John
AU - Mondoro, Traci Heath
AU - Weinmann, Gail
AU - Troendle, James
AU - Berdan, Lisa G.
AU - Aggarwal, Neil
AU - Bernard, Gordon
AU - Brown, Samuel Morris
AU - Callaway, Cliff
AU - Collins, Sean
AU - Cushman, Mary
AU - Douglas, David
AU - Erzurum, Serpil
AU - Farrell, Ann
AU - Gelijns, Annetine
AU - Ginde, Adit
AU - Glynn, Simone
AU - Goff, David
AU - Harrigan, Rachel
AU - Harrington, Robert
AU - Hochman, Judy
AU - Homer, Mary
AU - Johnson, Robert
AU - Key, Nigel
AU - Kiley, James
AU - Koroshetz, Walter
AU - Lane, Cliff
AU - LaVange, Lisa
AU - Marks, Gilbert Lynn
AU - Marks, Peter
AU - Mensah, George
AU - Nugent, Diane
AU - Patterson, Amy
AU - Rosenberg, Yves
AU - Shotwell, Matt
AU - Silverman, Toby
AU - Stoney, Catherine
AU - Wright, Clinton
AU - Yancy, Clyde
AU - Nolen, Tracy
AU - Thomas, Sonia
AU - Walter, Michelle
AU - Herring, Greta
AU - Kendrick, Amy
AU - Deese, Jen
AU - Sullivan, Taegen
AU - Mooberry, Micah
AU - Moll, Stephan
AU - Abajas, Yasmina
AU - Brightwood, Amy
AU - Stanford, Katie
AU - Finerty, Laura
AU - Chaffins, Lesia
AU - Nercesian, Marianna
AU - Dolor, Rowena
AU - Dreyer, Grace
AU - Der, Tatyana
AU - Ko, Emily
AU - Archibald, Andrea
AU - Renard, Valerie
AU - Stafford, Neil
AU - Azuogalanya, Nkiruka
AU - Mohammed, Oluwayemisi
AU - McPherson, Charles
AU - Choye, Peggy
AU - Kim, Keri
AU - Atal, Neha
AU - Mon, Ana
AU - Garg, Shamila
AU - Vrame, James
AU - Murawski, Trevor
AU - Khanna, Ashish
AU - Wadhwani, Hinna
AU - Sanfilippo, Kristen
AU - Buettner, Benjamin
AU - Mullick, Monalisa
AU - Bruinsma, Monique
N1 - Publisher Copyright:
© 2023 American College of Physicians.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85152621860&partnerID=8YFLogxK
U2 - 10.7326/M22-3350
DO - 10.7326/M22-3350
M3 - Article
C2 - 36940444
AN - SCOPUS:85152621860
SN - 0003-4819
VL - 176
SP - 515
EP - 523
JO - Annals of internal medicine
JF - Annals of internal medicine
IS - 4
ER -