Dataset Information

High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis.

ABSTRACT: Thromboprophylaxis in hospitalized patients with COVID-19 has been associated with a survival benefit and is strongly recommended. However, the optimal dose of thromboprophylaxis remains unclear. A systematic review and meta-analysis (PubMed/EMBASE) of studies comparing high (intermediate or therapeutic dose) versus standard (prophylactic dose) intensity of thrombo-prophylaxis with regard to outcome of hospitalized patients with COVID-19 was performed. Randomized and non-randomized studies that provided adjusted effect size estimates were included. Meta-analysis of 7 studies comparing intermediate versus prophylactic dose of thromboprophylaxis (2 randomized and 5 observational, n = 2009, weighted age 61 years, males 61%, ICU 53%) revealed a pooled adjusted relative risk (RR) for death at 0.56 (95% confidence intervals (CI) 0.34, 0.92) in favor of the intermediate dose. For the same comparison arms, the pooled RR for venous thromboembolism was 0.84 (95% CI 0.54, 1.31), and for major bleeding events was 1.63 (95% CI 0.79, 3.37). Meta-analysis of 17 studies comparing therapeutic versus prophylactic dose of thromboprophylaxis (2 randomized and 15 observational, n = 7776, weighted age 64 years, males 54%, ICU 21%) revealed a pooled adjusted RR for death at 0.73 (95% CI 0.47, 1.14) for the therapeutic dose. An opposite trend was observed in the unadjusted analysis of 15 observational studies (RR 1.24 (95% CI 0.88, 1.74)). For the same comparison arms, the pooled RR for venous thromboembolism was 1.13 (95% CI 0.52, 2.48), and for major bleeding events 3.32 (95% CI 2.51, 4.40). In conclusion, intermediate compared with standard prophylactic dose of thromboprophylaxis appears to be rather safe and is associated with additional survival benefit, although most data are derived from observational retrospective analyses. Randomized studies are needed to define the optimal thromboprophylaxis in hospitalized patients with COVID-19.

SUBMITTER: Kollias A

PROVIDER: S-EPMC8658422 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The prevalence of venous thromboembolism is high in patients with COVID-19, despite prophylactic anticoagulation. The evidence that supports the preferred thromboprophylaxis regimen in non-critically ill patients with mild to moderate COVID-19 is still limited. Therefore, this systematic review and meta-analysis aimed to compare the clinical outcomes of hospitalized patients with mild to moderate COVID-19 who received standard thromboprophylaxis anticoagulation with intermediate to high prophylaxis regimens. We systematically searched MEDLINE and Embase databases for published studies until August 17th, 2022. We included studies on patients with mild to moderate COVID-19 who received thromboprophylaxis during their hospital stay. Patients who received standard prophylaxis dose "control group" were compared to patients who received intermediate to high prophylaxis "intervention group". Random effect models were used when pooling crude numbers and adjusted effect estimates of study outcomes. A comprehensive analysis was conducted, encompassing seven studies involving a total of 1931 patients. The risk of all-cause thrombosis was not statistically different between the two groups (risk ratio [RR] 1.48, 95% confidence interval [CI] [0.11, 20.21]). The risk of minor bleeding was reported to be lower in patients who received intermediate to high prophylaxis (RR 0.64, 95% CI 0.21, 1.97), while had a higher risk of major bleeding compared with the standard prophylaxis (RR 1.40, 95% CI 0.43, 4.61); however, did not reach the statistical significance. The overall risk for all hospital mortality favored the utilization of intermediate to high doses over the standard thromboprophylaxis dosing (RR 0.47, 95%CI 0.29, 0.75). In medically ill patients with COVID-19, there is no difference between standard and intermediate to high prophylaxis dosing regarding thrombosis and bleeding. However, it appears that intermediate to high prophylaxis regimens are linked to additional survival benefits.

Project description:ImportanceHospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown.ObjectiveTo evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19.Design, setting, and participantsThe HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US.InterventionsPatients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status.Main outcomes and measuresThe primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data.ResultsOf 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71).Conclusions and relevanceIn this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients.Trial registrationClinicalTrials.gov Identifier: NCT04401293.

Project description:The reported incidence rate of venous and arterial thrombotic events in critically ill patients with COVID-19 infections is high, ranging from 20% to 60%. We adopted a patient-tailored thromboprophylaxis protocol based on clinical and laboratory presentations for these patients in our institution. We hypothesised that patients who received high-intensity thromboprophylaxis treatment would experience fewer thrombotic events. The aims of our study were to explore the incidence of thrombotic events in this population; to assess independent factors associated with thrombotic events and to evaluate the incidence of haemorrhagic events. A retrospective review of all adult patients with confirmed SARS-CoV-2 infection admitted to the intensive care unit (ICU) between 1 March and 29 May 2020 was performed. The primary outcome was a composite of venous and arterial thrombotic events diagnosed during the ICU stay. Multivariable logistic regression was used to identify the independent factors associated with thrombotic events. A total of 188 patients met the inclusion criteria. All received some type of thromboprophylaxis treatment except for six patients who did not receive any prophylaxis. Of the 182 patients who received thromboprophylaxis, 75 (40%) received high-intensity thromboprophylaxis and 24 (12.8%) were treated with therapeutic anticoagulation. Twenty-one patients (11.2%) experienced 23 thrombotic events (incidence rate of 12.2% (95%CI 7.9-17.8)), including 12 deep venous thromboses, 9 pulmonary emboli and 2 peripheral arterial thromboses. The multivariable logistic regression analysis showed that only D-dimer (OR 2.80, p = 0.002) and high-intensity thromboprophylaxis regimen (OR 0.20, p = 0.01) were independently associated with thrombotic events. Thirty-one patients (16.5%) experienced haemorrhagic events; among them, 13 were classified as major bleeding according to the International Society on Thrombosis and Haemostasis criteria. Therapeutic anticoagulation, but not the high-intensity thromboprophylaxis regimen, was associated with major bleeding. A proactive approach to the management of thromboembolism in critically ill COVID-19 patients utilising a high-intensity thromboprophylaxis regimen in appropriately selected patients may result in lower thrombotic events without increasing the risk of bleeding.

Project description:Background Coronavirus disease 2019 (COVID-19) increases thrombosis in hospitalized patients prompting adoption of different thromboprophylaxis strategies. Safety and efficacy of escalated-dose pharmacologic thromboprophylaxis are not established.Objectives To determine the pooled incidence of thrombosis/bleeding in hospitalized patients with COVID-19 for standard-dose, intermediate-dose, therapeutic anticoagulation, and no pharmacologic thromboprophylaxis.Methods MEDLINE, EMBASE, and Cochrane CENTRAL were searched up to August 29, 2020 for studies reporting pharmacologic thromboprophylaxis and thrombosis or bleeding. Pooled event rates were calculated using a random-effects model.Results Thirty-five observational studies were included. The pooled incidence rates of total venous thromboembolism (N = 4,685) were: no prophylaxis 41.9% (95% confidence interval [CI]: 28.1-57.2, I 2 = 76%), standard-dose prophylaxis 19.8% (95% CI: 13.2-28.6, I 2 = 95%), intermediate-dose prophylaxis 11.9% (95% CI: 4.3-28.6, I 2 = 91%), and therapeutic-dose anticoagulants 10.5% (95% CI: 4.2-23.8, I 2 = 82%, p = 0.003). The pooled incidence rates of arterial thrombosis (N = 1,464) were: no prophylaxis 11.3% (95% CI: 5.2-23.0, I 2 = 0%), standard-dose prophylaxis 2.5% (95% CI: 1.4-4.3, I 2 = 45%), intermediate-dose prophylaxis 2.1% (95% CI: 0.5-7.7, I 2 = 45%), and therapeutic-dose anticoagulants 1.3% (95% CI: 0.2-8.8, I 2 = 0, p = 0.009). The pooled bleeding event rates (N = 6,393) were nonsignificantly higher in therapeutic-dose anticoagulants compared with standard-dose prophylaxis, (6.3 vs. 1.7%, p = 0.083).Conclusion Thrombosis rates were lower in hospitalized COVID-19 patients who received pharmacologic thromboprophylaxis. Thrombosis and bleeding rates for patients receiving intermediate-dose thromboprophylaxis or therapeutic anticoagulation were similar to those who received standard-dose pharmacologic thromboprophylaxis.

Dataset Information

High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets