Semin Thromb Hemost 2021; 47(04): 372-391
DOI: 10.1055/s-0041-1726034
Review Article

Different Anticoagulant Regimens, Mortality, and Bleeding in Hospitalized Patients with COVID-19: A Systematic Review and an Updated Meta-Analysis

Roberta Parisi
1   Department of Epidemiology and Prevention. IRCCS Neuromed, via dell'Elettronica, Pozzilli, Isernia, Italy
Simona Costanzo
1   Department of Epidemiology and Prevention. IRCCS Neuromed, via dell'Elettronica, Pozzilli, Isernia, Italy
Augusto Di Castelnuovo
2   Mediterranea Cardiocentro, Via Orazio n.2, Napoli, Italy
Giovanni de Gaetano
1   Department of Epidemiology and Prevention. IRCCS Neuromed, via dell'Elettronica, Pozzilli, Isernia, Italy
Maria Benedetta Donati
1   Department of Epidemiology and Prevention. IRCCS Neuromed, via dell'Elettronica, Pozzilli, Isernia, Italy
Licia Iacoviello
1   Department of Epidemiology and Prevention. IRCCS Neuromed, via dell'Elettronica, Pozzilli, Isernia, Italy
3   Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, Varese, Italy
› Author Affiliations
Funding None.


We conducted a systematic review and a meta-analysis to assess the association of anticoagulants and their dosage with in-hospital all-cause mortality in COVID-19 patients. Articles were retrieved until January 8, 2021, by searching in seven electronic databases. The main outcome was all-cause mortality occurred during hospitalization. Data were combined using the general variance-based method on the effect estimate for each study. Separate meta-analyses according to type of COVID-19 patients (hospitalized or intensive care unit [ICU] patients), anticoagulants (mainly heparin), and regimens (therapeutic or prophylactic) were conducted. A total of 29 articles were selected, but 23 retrospective studies were eligible for quantitative meta-analyses. No clinical trial was retrieved. The majority of studies were of good quality; however, 34% did not distinguish heparin from other anticoagulants. Meta-analysis on 25,719 hospitalized COVID-19 patients showed that anticoagulant use was associated with 50% reduced in-hospital mortality risk (pooled risk ratio [RR]: 0.50, 95% confidence interval [CI]: 0.40–0.62; I 2: 87%). Both anticoagulant regimens (therapeutic and prophylactic) reduced in-hospital all-cause mortality, compared with no anticoagulation. Particularly in ICU patients, the anticoagulant therapeutic regimen was associated with a reduced in-hospital mortality risk (RR: 0.30, 95% CI: 0.15–0.60; I 2: 58%) compared with the prophylactic one. However, the former was also associated with a higher risk of bleeding (RR: 2.53, 95% CI: 1.60–4.00; I 2: 65%). Anticoagulant use, mainly heparin, reduced all-cause mortality in COVID-19 patients during hospitalization. Due to the higher risk of bleeding at therapeutic doses, the use of prophylactic dosages of anticoagulant is probably to be preferred in noncritically ill COVID-19 patients.

Authors' Contributions

S.C. and L.I. contributed to the conception and design of the work and interpretation of data; R.P., S.C., and A.D.C. managed study selection and data extraction and critically reviewed the results; R.P. analyzed the data; R.P. and S.C. wrote the paper; L.I., G.d.G., and M.B.D. originally inspired the research and critically reviewed the manuscript. All authors approved the final version of the manuscript.

Supplementary Material

Publication History

Article published online:
13 April 2021

© 2021. Thieme. All rights reserved.

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