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Meta-Analysis
. 2023 Apr;201(2):135-147.
doi: 10.1007/s00408-023-00599-6. Epub 2023 Feb 4.

The Effect of Heparin Full-Dose Anticoagulation on Survival of Hospitalized, Non-critically Ill COVID-19 Patients: A Meta-analysis of High Quality Studies

Eros Pilia  1   2 , Alessandro Belletti  3 , Stefano Fresilli  3 , Todd C Lee  4 , Alberto Zangrillo  3   5 , Gabriele Finco  1   2 , Giovanni Landoni  6   7 ; full anticoagulation
Collaborators, Affiliations
Meta-Analysis

The Effect of Heparin Full-Dose Anticoagulation on Survival of Hospitalized, Non-critically Ill COVID-19 Patients: A Meta-analysis of High Quality Studies

Eros Pilia et al. Lung. 2023 Apr.

Abstract

Background: International COVID-19 guidelines recommend thromboprophylaxis for non-critically ill inpatients to prevent thrombotic complications. It is still debated whether full-dose thromboprophylaxis reduces all-cause mortality. The main aim of this updated systematic review and meta-analysis is to evaluate the effect of full-dose heparin-based thromboprophylaxis on survival in hospitalized non-critically ill COVID-19 patients.

Methods: A systematic review was performed across Pubmed/Medline, EMBASE, Cochrane Central Register of clinical trials, Clinicaltrials.gov, and medRxiv.org from inception to November 2022. We conducted a meta-analysis of randomized clinical trials (RCTs) comparing full-dose heparin-based anticoagulation to prophylactic or intermediate dose anticoagulation or standard treatment in hospitalized non-critically ill COVID-19 patients. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations Assessment, Development and Evaluation was applied. The primary outcome was all-cause mortality at the longest follow-up available.

Results: We identified 6 multicenter RCTs involving 3297 patients from 13 countries across 4 continents. The rate of all-cause mortality was 6.2% (103/1662) in the full-dose group vs 7.7% (126/1635) in the prophylactic or intermediate dose group (Risk Ratio [RR] = 0.76; 95% confidence interval [CI] = 0.59-0.98; P = 0.037). The probabilities of any mortality difference and of NNT ≤ 100 were estimated at 98.2% and 84.5%, respectively. The risk of bias was low for all included RCTs and the strength of the evidence was "moderate."

Conclusion: Our meta-analysis of high-quality multicenter RCTs suggests that full-dose anticoagulation with heparin or low molecular weight heparin reduces all-cause mortality in hospitalized non-critically ill COVID-19 patients.

Study registration: PROSPERO, review no. CRD42022348993.

Keywords: Anticoagulant; COVID-19; Heparin; Hospital mortality; LMWH; SARS-CoV-2.

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Conflict of interest statement

The authors declare they have no conflict of interest.

Figures

Fig. 1
Fig. 1
PRISMA diagram
Fig. 2
Fig. 2
Traffic plot of mRCTs included in the meta-analysis
Fig. 3
Fig. 3
Forest plot of the rate of all-cause mortality at the longest follow-up available
Fig. 4
Fig. 4
Forest plot of the rate of major arterial and venous thrombotic events
Fig. 5
Fig. 5
Forest plot of the rate of major bleeding events
See this image and copyright information in PMC

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