Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19
Godoy, Lucas C.; Neal, Matthew D.; Goligher, Ewan C.; Cushman, Mary; Houston, Brett L.; Bradbury, Charlotte A.; McQuilten, Zoe K.; Tritschler, Tobias; Kahn, Susan R.; Berry, Lindsay R.; Lorenzi, Elizabeth; Jensen, Tom; Higgins, Alisa M.; Kornblith, Lucy Z.; Berger, Jeffrey S.; Gong, Michelle N.; Paul, Jonathan D.; Castellucci, Lana A.; Le Gal, Grégoire; Lother, Sylvain A.; Rosenson, Robert S.; Derde, Lennie P.G.; Kumar, Anand; McVerry, Bryan J.; Nicolau, Jose C.; Leifer, Eric; Escobedo, Jorge; Huang, David T.; Reynolds, Harmony R.; Carrier, Marc; Kim, Keri S.; Hunt, Beverley J.; Slutsky, Arthur S.; Turgeon, Alexis F.; Webb, Steven A.; McArthur, Colin J.; Farkouh, Michael E.; Hochman, Judith S.; Zarychanski, Ryan; Lawler, Patrick R.
(2024) JACC: Advances, volume 3, issue 3, pp.
(Article)
Abstract
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)
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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.
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Keywords: anticoagulation, clinical trial, COVID-19, heparin, thrombosis, Cardiology and Cardiovascular Medicine, Dentistry (miscellaneous), Journal Article
ISSN: 2772-963X
Publisher: Elsevier
Note: Publisher Copyright: © 2024 The Authors
(Peer reviewed)