Efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients: a meta-analysis of multicenter randomized controlled trials

Pilia, Eros; Belletti, Alessandro; Fresilli, Stefano; Finco, Gabriele; Landoni, Giovanni

doi:10.1007/s11239-022-02681-x

Cited by 20 publications

(22 citation statements)

References 32 publications

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“…Five previously published meta-analyses studied the effect of anticoagulant regimens with low-molecular-weight heparin in hospitalized patients with Covid-19 [ 22 – 26 ]. Neither of the meta-analysis demonstrated benefits in terms of mortality in patients receiving full-dose anticoagulation compared with thromboprophylaxis.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials

Ena

Valls

2022

Clin Exp Med

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Background We carried out a meta-analysis since there is not enough evidence to recommend for or against therapeutic-dose anticoagulation compared with thromboprophylaxis in noncritically ill patients hospitalized with Covid-19. Methods We performed a systematic literature search using PubMed, Embase, Cochrane Library, and MedRxiv for randomized trials that included therapeutic-dose with low-molecular-weight heparin (LMW) or thromboprophylaxis with LMW heparin in noncritically ill patients admitted to the hospital with Covid-19. We identified five open-label studies for analysis with a total of 3220 patients. Two independent researchers selected, assessed, and extracted the data in duplicate. The outcomes evaluated were all-cause mortality, progression to invasive mechanical ventilation, incidence of venous thromboembolism, and major bleeding. The studies did not show risk for selection, detection, attrition, or reporting bias. Results Therapeutic-dose anticoagulation with LMW heparin compared with thromboprophylaxis with LMW heparin had no significant effect of all-cause death (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.67–1.07; P = 0.16; I 2 = 48%), or progression to invasive mechanical ventilation (RR 0.89; CI 0.73–1.08; P = 0.24; I 2 : 0%). Therapeutic-dose anticoagulation significantly reduced the risk of venous thromboembolic disease (RR 0.42; 95% CI 0.28–0.62; P = 0.0001; I 2 = 0%) [Number needed to treat = 37]. Major bleeding occurred in 1.79% of the patients receiving therapeutic-dose anticoagulation and in 0.97% of those receiving thromboprophylaxis [Number needed to harm 125]. Conclusion Therapeutic-dose anticoagulation in noncritically ill patients with Covid-19 could be indicated for patients at high risk of venous thromboembolic disease and low risk of bleeding.

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Section: Discussionmentioning

confidence: 99%

Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials

Ena

Valls

2022

Clin Exp Med

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“…After consideration of evidence from additional six randomised trials (RCTs)—two on the effects of direct acting anticoagulant (DOAC) rivaroxaban and four related to prophylaxis with LMWH, 26–31 the panel updated its recommendation in May of 2022 25 in favour of therapeutic intensity anticoagulation with LMWH for acutely but not critically ill hospitalised patients with COVID‐19. The recommendations are consistent with two meta‐analyses of RCTs, which indicated beneficial effects of therapeutic intensity anticoagulation in terms of reduction of VTE but no significant effect on overall mortality and major bleeding 32,33 . However, on both occasions, the panel assessed that recommendations was based on very low certainty in the evidence, acknowledging that administration of the prophylactic LMWH is also appropriate, particularly in patients considered at the lower risk 34 for COVID‐19 complications or higher bleeding risk 24,25 .…”

Section: Methodsmentioning

confidence: 63%

Evaluation of a fast‐and‐frugal clinical decision algorithm (‘pathways’) on clinical outcomes in hospitalised patients with COVID‐19 treated with anticoagulants

Djulbegoviĉ

Hozo

Lizarraga

et al. 2022

Evaluation Clinical Practice

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Rationale, Aims and Objectives Critics have charged that evidence‐based medicine (EBM) overemphasises algorithmic rules over unstructured clinical experience and intuition, but the role of structured decision support systems in improving health outcomes remains uncertain. We aim to assess if delivery of anticoagulant prophylaxis in hospitalised patients with COVID‐19 according to an algorithm based on evidence‐based clinical practice guideline (CPG) improved clinical outcomes compared with administration of anticoagulant treatment given at individual practitioners' discretion. Methods An observational design consisting of the analysis of all acutely ill, consecutive patients (n = 1783) with confirmed COVID‐19 diagnosis admitted between 10 March 2020 to 11 January 2022 to an US academic center. American Society of Haematology CPG for anticoagulant prophylaxis in hospitalised patients with COVID‐19 was converted into a clinical pathway and translated into fast‐and‐frugal decision (FFT) tree (‘algorithm’). We compared delivery of anticoagulant prophylaxis in hospitalised patients with COVID‐19 according to the FFT algorithm with administration of anticoagulant treatment given at individual practitioners' discretion. Results In an adjusted analysis, using combination of Lasso (least absolute shrinkage and selection operator) and propensity score based weighting [augmented inverse‐probability weighting] statistical techniques controlling for cluster data, the algorithm did not reduce death, venous thromboembolism, or major bleeding, but helped avoid longer hospital stay [number of patients needed to be treated (NNT) = 40 (95% CI: 23–143), indicating that for every 40 patients (23–143) managed on FFT algorithm, one avoided staying in hospital longer than 10 days] and averted admission to intensive‐care unit (ICU) [NNT = 19 (95% CI: 13–40)]. All model's selected covariates were well balanced. The results remained robust to sensitivity analyses used to test the stability of the findings. Conclusions When delivered using a structured FFT algorithm, CPG shortened the hospital stay and help avoided admission to ICU, but it did not affect other relevant outcomes.

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“…Most guidelines initially recommended prophylactic dose anticoagulation for hospitalized patients and the consideration of a higher dose regimen in those at increased VTE risk [ 16 ]. The most recent formal guidelines using accepted methodology from the ISTH [ 17 ] and guidance from American College of Chest Physicians (ACCP/CHEST) [ 21 ] provide an updated approach based on recent findings from RCTs and meta-analyses [ 48 ]. The CHEST clinical guidance suggests that the severity of COVID-19 should be assessed before a decision for thromboprophylaxis [ 21 ].…”

Section: Results—key Questions and Practical Recommendationsmentioning

confidence: 99%

Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19: A Consensus Statement Based on Available Clinical Trials

Kyriakoulis

Dimakakos

Kyriakoulis

et al. 2022

JCM

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Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients.

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Efficacy and safety of heparin full-dose anticoagulation in hospitalized non-critically ill COVID-19 patients: a meta-analysis of multicenter randomized controlled trials

Cited by 20 publications

References 32 publications

Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials

Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials

Evaluation of a fast‐and‐frugal clinical decision algorithm (‘pathways’) on clinical outcomes in hospitalised patients with COVID‐19 treated with anticoagulants

Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19: A Consensus Statement Based on Available Clinical Trials

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