Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19

Lucas C. Godoy, Matthew D. Neal, Ewan C. Goligher, Mary Cushman, Brett L. Houston, Charlotte A. Bradbury, Zoe K. McQuilten, Tobias Tritschler, Susan R. Kahn, Lindsay R. Berry, Elizabeth Lorenzi, Tom Jensen, Alisa M. Higgins, Lucy Z. Kornblith, Jeffrey S. Berger, Michelle N. Gong, Jonathan D. Paul, Lana A. Castellucci, Grégoire Le Gal, Sylvain A. LotherRobert S. Rosenson, Lennie P.G. Derde, Anand Kumar, Bryan J. McVerry, Jose C. Nicolau, Eric Leifer, Jorge Escobedo, David T. Huang, Harmony R. Reynolds, Marc Carrier, Keri S. Kim, Beverley J. Hunt, Arthur S. Slutsky, Alexis F. Turgeon, Steven A. Webb, Colin J. McArthur, Michael E. Farkouh, Judith S. Hochman, Ryan Zarychanski, Patrick R. Lawler

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.

Original languageEnglish
Article number100780
JournalJACC: Advances
Issue number3
StatePublished - Mar 2024


  • COVID-19
  • anticoagulation
  • clinical trial
  • heparin
  • thrombosis


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