The effect of higher-intensity dosing of anticoagulation on the clinical outcomes in hospitalized patients with COVID-19: A meta-analysis of randomized controlled trials

Kow, Chia Siang; Ramachandram, Dinesh Sangarran; Hasan, Syed Shahzad

doi:10.1016/j.jiac.2021.11.008

Cited by 23 publications

(22 citation statements)

References 18 publications

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“…Our analysis found significant reductions in VTE only in trials that included non-critically ill patients (which all provided therapeutic doses of anticoagulation); this was accompanied by a signal of mortality reduction not seen in trials conducted in the ICU, although with significant between-study heterogeneity. Smaller meta-analyses investigating anticoagulation in Covid-19 have also reported a trend towards reduced mortality in non-critically ill patients only [41–43]. These findings suggest that a window may exist earlier in the disease course of Covid-19 for optimal timing of anticoagulation to prevent VTE and avert disease progression via reduction of pulmonary microthrombosis and pleotropic effects of heparin.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: a systematic review and meta-analysis

Wills

Nair

Patel

et al. 2022

Preprint

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Background Randomised controlled trials (RCTs) have reported inconsistent effects from intensified anticoagulation on clinical outcomes in Covid-19. We performed an aggregate data meta-analysis from available trials to quantify effect on non-fatal and fatal outcomes and identify subgroups who may benefit. Methods We searched multiple databases for RCTs comparing intensified (intermediate or therapeutic dose) versus standard prophylactic dose anticoagulation in adults with laboratory-confirmed Covid-19 through 19 January 2022. The primary efficacy outcome was all-cause mortality at end of follow-up or discharge. We used random effects meta-analysis to estimate pooled risk ratios for mortality, thrombotic, and bleeding events, and performed subgroup analysis for clinical setting and dose of intensified anticoagulation. Results Eleven RCTs were included (n = 5873). Intensified anticoagulation was not associated with a reduction in mortality for up to 45 days compared with prophylactic anticoagulation: 17.5% (501/2861) died in the intensified anticoagulation group and 18.8% (513/2734) died in the prophylactic anticoagulation group, relative risk (RR) 0.93; 95%CI, 0.79 – 1.10. On subgroup analysis, there was a possible signal of mortality reduction for inpatients admitted to general wards, although with low precision and high heterogeneity (5 studies; RR 0.84; 95% CI, 0.49 – 1.44; I2 = 75%) and not significantly different to studies performed in the ICU (interaction P = 0.51). Risk of venous thromboembolism was reduced with intensified anticoagulation compared with prophylaxis (8 studies; RR 0.53, 95%CI 0.41 – 0.69; I2 = 0%). This effect was driven by therapeutic rather than intermediate dosing on subgroup analysis (interaction P = 0.04). Major bleeding was increased with use of intensified anticoagulation (RR 1.73, 95% CI 1.17 – 2.56) with no interaction for dosing and clinical setting. Conclusion Intensified anticoagulation has no effect on short term mortality among hospitalised adults with Covid-19 and is associated with increased risk of bleeding. The observed reduction in venous thromboembolism risk and trend towards reduced mortality in non-ICU hospitalised patients requires exploration in additional RCTs.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: a systematic review and meta-analysis

Wills

Nair

Patel

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…An increase in bleeding was also observed [ 69 , 70 , 71 ]. The studies we discussed [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ] and the available meta-analyses [ 62 , 63 , 64 , 65 , 66 ] revealed the need for a tailored anticoagulant therapy. Heparin was shown to reduce mortality both at prophylactic and therapeutic dosages; however, an increase in bleeding was reported [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

“…The failure to reduce mortality in severe patients seemed to be due to a delayed start of therapy. No trial evaluated the risk of individual bleeding; therefore, this could explain the observed increase in major bleeding [ 62 ].…”

Section: Evidence Of Heparin Use In Covid-19 Acute Illnessmentioning

confidence: 99%

The Role of Heparin in COVID-19: An Update after Two Years of Pandemics

Mangiafico

Caff

Costanzo

2022

JCM

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Coronavirus disease 2019 (COVID-19) is associated with an increased risk of venous thromboembolism (VTE) and coagulopathy, especially in critically ill patients. Endothelial damage induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as a crucial pathogenetic mechanism for the development of complications in an acute phase of the illness and for several postdischarge sequalae. Heparin has been shown to have a positive impact on COVID-19 due to its anticoagulant function. Moreover, several other biological actions of heparin were postulated: a potential anti-inflammatory and antiviral effect through the main protease (Mpro) and heparansulfate (HS) binding and a protection from the damage of vascular endothelial cells. In this paper, we reviewed available evidence on heparin treatment in COVID-19 acute illness and chronic sequalae, focusing on the difference between prophylactic and therapeutic dosage.

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“…Results of meta-analyses published showed controversial results, therapeutic anticoagulation doses may be better for non-critically ill patients, without benefits for critically ill patients [ 42 , 43 , 44 ].…”

Section: Anticoagulant Treatmentmentioning

confidence: 99%

Anticoagulant Treatment in Severe ARDS COVID-19 Patients

Ceccato

Camprubí-Rimblas

Campaña-Duel

et al. 2022

JCM

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Patients with COVID-19 may complicate their evolution with thromboembolic events. Incidence of thromboembolic complications are high and also, patients with the critically-ill disease showed evidence of microthrombi and microangiopathy in the lung probably due to endothelial damage by directly and indirectly injured endothelial and epithelial cells. Pulmonary embolism, deep venous thrombosis and arterial embolism were reported in patients with COVID-19, and several analytical abnormal coagulation parameters have been described as well. D-dimer, longer coagulation times and lower platelet counts have been associated with poor outcomes. The use of anticoagulation or high doses of prophylactic heparin is controversial. Despite the use of anticoagulation or high prophylactic dose of heparin have been associated with better outcomes in observational studies, only in patients with non-critically ill disease benefits for anticoagulation was observed. In critically-ill patient, anticoagulation was not associated with better outcomes. Other measures such as antiplatelet therapy, fibrinolytic therapy or nebulized anticoagulants are being studied in ongoing clinical trials.

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The effect of higher-intensity dosing of anticoagulation on the clinical outcomes in hospitalized patients with COVID-19: A meta-analysis of randomized controlled trials

Cited by 23 publications

References 18 publications

Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: a systematic review and meta-analysis

Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: a systematic review and meta-analysis

The Role of Heparin in COVID-19: An Update after Two Years of Pandemics

Anticoagulant Treatment in Severe ARDS COVID-19 Patients

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