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Meta-Analysis
. 2022 Sep 29;8(7):677-686.
doi: 10.1093/ehjcvp/pvab070.

Safety and efficacy of different prophylactic anticoagulation dosing regimens in critically and non-critically ill patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials

Luis Ortega-Paz  1 , Mattia Galli  2   3 , Davide Capodanno  4 , Francesco Franchi  3 , Fabiana Rollini  3 , Behnood Bikdeli  5   6   7 , Roxana Mehran  8 , Gilles Montalescot  9 , C Michael Gibson  10 , Renato D Lopes  11   12 , Felicita Andreotti  2 , Dominick J Angiolillo  3
Affiliations
Meta-Analysis

Safety and efficacy of different prophylactic anticoagulation dosing regimens in critically and non-critically ill patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials

Luis Ortega-Paz et al. Eur Heart J Cardiovasc Pharmacother. .

Abstract

Background: The clinical impact of different prophylactic anticoagulation regimens among hospitalized patients with coronavirus disease 2019 (COVID-19) remains unclear. We pooled evidence from available randomized controlled trials (RCTs) to provide insights on this topic.

Methods and results: We searched for RCTs comparing treatment with an escalated-dose (intermediate-dose or therapeutic-dose) vs. a standard-dose prophylactic anticoagulation regimen in critically and non-critically ill COVID-19 patients requiring hospitalization and without a formal indication for anticoagulation. The primary efficacy endpoint was all-cause death, and the primary safety endpoint was major bleeding. Seven RCTs were identified, including 5154 patients followed on an average of 33 days. Compared to standard-dose prophylactic anticoagulation, escalated-dose prophylactic anticoagulation was not associated with a reduction of all-cause death [17.8% vs. 18.6%; risk ratio (RR) 0.96, 95% confidence interval (CI) 0.78-1.18] but was associated with an increase in major bleeding (2.4% vs. 1.4%; RR 1.73, 95%CI 1.15-2.60). Compared to prophylactic anticoagulation used at a standard dose, an escalated dose was associated with lower rates of venous thromboembolism (2.5% vs. 4.7%; RR 0.55, 95%CI 0.41-0.74) without a significant effect on myocardial infarction (RR 0.80, 95%CI 0.47-1.36), stroke (RR 0.94, 95%CI 0.43-2.09), or systemic arterial embolism (RR 1.20, 95%CI 0.29-4.95). There were no significant interactions in the subgroup analysis for critically and non-critically ill patients.

Conclusions: Our findings provide comprehensive and high-quality evidence for the use of standard-dose prophylactic anticoagulation over an escalated-dose regimen as routine standard of care for hospitalized patients with COVID-19 who do not have an indication for therapeutic anticoagulation, irrespective of disease severity.

Study registration: This study is registered in PROSPERO (CRD42021257203).

Keywords: Anticoagulant therapy; Bleeding; Coronavirus disease 2019; Death; Thrombosis.

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Figures

Figure 1.
Figure 1.
Forest plots according to pre-specified subgroups (critically vs. non-critically ill) of escalated-dose vs. standard-dose prophylactic anticoagulation for the primary efficacy (all-cause death) and safety (major bleeding) endpoints. CI = confidence intervals; M-H = Mantel-Haenszel; IV = inverse variance.
Figure 2.
Figure 2.
Forest plots according to pre-specified subgroups (critically vs. non-critically ill) of escalated-dose vs. standard-dose prophylactic anticoagulation for venous thromboembolism and arterial thrombosis events. CI = confidence intervals; M-H = Mantel-Haenszel; IV = inverse variance.
Figure 3.
Figure 3.
Forest plots according to pre-specified subgroups (critically vs. non-critically ill) of escalated-dose vs. standard-dose prophylactic anticoagulation for any and minor bleeding. CI = confidence intervals; M-H = Mantel-Haenszel, IV = inverse variance.
Figure 4.
Figure 4.
Number needed to treat (NNT) and number needed to harm (NNH). VTE = venous thromboembolism; MI = myocardial infarction.
See this image and copyright information in PMC

Comment in

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