Randomized trials of therapeutic heparin for COVID-19: A meta-analysis.

Sholzberg, Michelle; Da Costa, Bruno R.; Tang, Grace H; Rahhal, Hassan; AlHamzah, Musaad; Baumann Kreuziger, Lisa; Ní Áinle, Fionnuala; Almarshoodi, Mozah Obaid; James, Paula D; Lillicrap, David; Carrier, Marc; Beckett, Andrew; Fralick, Michael; Middeldorp, Saskia; Lee, Agnes Y Y; Thorpe, Kevin E; Negri, Elnara Márcia; Cushman, Mary; Jüni, Peter (2021). Randomized trials of therapeutic heparin for COVID-19: A meta-analysis. Research and practice in thrombosis and haemostasis, 5(8), e12638. Wiley 10.1002/rth2.12638

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Pulmonary endothelial injury and microcirculatory thromboses likely contribute to hypoxemic respiratory failure, the most common cause of death, in patients with COVID-19. Randomized controlled trials (RCTs) suggest differences in the effect of therapeutic heparin between moderately and severely ill patients with COVID-19. We did a systematic review and meta-analysis of RCTs to determine the effects of therapeutic heparin in hospitalized patients with COVID-19.


We searched PubMed, Embase, Web of Science, medRxiv, and medical conference proceedings for RCTs comparing therapeutic heparin with usual care, excluding trials that used oral anticoagulation or intermediate doses of heparin in the experimental arm. Mantel-Haenszel fixed-effect meta-analysis was used to combine odds ratios (ORs).

Results and Conclusions

There were 3 RCTs that compared therapeutic heparin to lower doses of heparin in 2854 moderately ill ward patients, and 3 RCTs in 1191 severely ill patients receiving critical care. In moderately ill patients, there was a nonsignificant reduction in all-cause death (OR, 0.76; 95% CI, 0.57-1.02), but significant reductions in the composite of death or invasive mechanical ventilation (OR, 0.77; 95% CI, 0.60 0.98), and death or any thrombotic event (OR, 0.58; 95% CI, 0.45-0.77). Organ support-free days alive (OR, 1.29; 95% CI, 1.07-1.57) were significantly increased with therapeutic heparin. There was a nonsignificant increase in major bleeding. In severely ill patients, there was no evidence for benefit of therapeutic heparin, with significant treatment-by-subgroup interactions with illness severity for all-cause death (P = .034). In conclusion, therapeutic heparin is beneficial in moderately ill patients but not in severely ill patients hospitalized with COVID-19.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)

UniBE Contributor:

Da Costa, Bruno


600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services








Doris Kopp Heim

Date Deposited:

06 Jan 2022 21:54

Last Modified:

05 Dec 2022 16:02

Publisher DOI:


PubMed ID:


Additional Information:

Sholzberg and da Costa contributed equally to this work.

Uncontrolled Keywords:

COVID‐19 anticoagulation clinical trials heparin meta‐analysis





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