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Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization.

Publication ,  Journal Article
Wang, TY; Wahed, AS; Morris, A; Kreuziger, LB; Quigley, JG; Lamas, GA; Weissman, AJ; Lopez-Sendon, J; Knudson, MM; Siegal, DM; Kasthuri, RS ...
Published in: Ann Intern Med
April 2023

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.

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Published In

Ann Intern Med

DOI

EISSN

1539-3704

Publication Date

April 2023

Volume

176

Issue

4

Start / End Page

515 / 523

Location

United States

Related Subject Headings

  • Venous Thromboembolism
  • Treatment Outcome
  • SARS-CoV-2
  • Prospective Studies
  • Middle Aged
  • Male
  • Humans
  • Hospitalization
  • Hemorrhage
  • General & Internal Medicine
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, T. Y., Wahed, A. S., Morris, A., Kreuziger, L. B., Quigley, J. G., Lamas, G. A., … ACTIV-4C Study Group. (2023). Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization. Ann Intern Med, 176(4), 515–523. https://doi.org/10.7326/M22-3350
Wang, Tracy Y., Abdus S. Wahed, Alison Morris, Lisa Baumann Kreuziger, John G. Quigley, Gervasio A. Lamas, Alexandra J. Weissman, et al. “Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization.Ann Intern Med 176, no. 4 (April 2023): 515–23. https://doi.org/10.7326/M22-3350.
Wang TY, Wahed AS, Morris A, Kreuziger LB, Quigley JG, Lamas GA, et al. Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization. Ann Intern Med. 2023 Apr;176(4):515–23.
Wang, Tracy Y., et al. “Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization.Ann Intern Med, vol. 176, no. 4, Apr. 2023, pp. 515–23. Pubmed, doi:10.7326/M22-3350.
Wang TY, Wahed AS, Morris A, Kreuziger LB, Quigley JG, Lamas GA, Weissman AJ, Lopez-Sendon J, Knudson MM, Siegal DM, Kasthuri RS, Alexander AJ, Wahid L, Atassi B, Miller PJ, Lawson JW, Patel B, Krishnan JA, Shapiro NL, Martin DE, Kindzelski AL, Leifer ES, Joo J, Lyu L, Pennella A, Everett BM, Geraci MW, Anstrom KJ, Ortel TL, ACTIV-4C Study Group. Effect of Thromboprophylaxis on Clinical Outcomes After COVID-19 Hospitalization. Ann Intern Med. 2023 Apr;176(4):515–523.

Published In

Ann Intern Med

DOI

EISSN

1539-3704

Publication Date

April 2023

Volume

176

Issue

4

Start / End Page

515 / 523

Location

United States

Related Subject Headings

  • Venous Thromboembolism
  • Treatment Outcome
  • SARS-CoV-2
  • Prospective Studies
  • Middle Aged
  • Male
  • Humans
  • Hospitalization
  • Hemorrhage
  • General & Internal Medicine