Standard Prophylactic Versus Intermediate Dose Enoxaparin in Adults with Severe COVID-19: A Multi-Center, Open-Label, Randomised Controlled Trial

Perepu, Usha; Chambers, Isaac; Wahab, Abdul; Eyck, Patrick Ten; Wu, Chaorong; Dayal, Sanjana; Sutamtewagul, Grerk; Bailey, Steven R.; Rosenstein, Lori J.; Lentz, Steven R.

doi:10.2139/ssrn.3840099

Cited by 6 publications

(9 citation statements)

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“…The effectiveness of anticoagulant dose escalation in COVID-19 ICU patients continues to be debated, even among RCT studies. Our findings are in line with the hypothesis that high-dose thromboprophylaxis has a similar composite of thrombotic events in critically ill patients with COVID-19 as intermediate-dose and standard-dose thromboprophylaxis regimens ( 29 , 31 , 32 ). In addition, parallel to observational and RCT studies ( 29 , 31 , 32 , 57 , 58 ), different thromboprophylaxis doses did not eliminate the risk of overall mortality.…”

Section: Discussionsupporting

confidence: 90%

“…Our findings are in line with the hypothesis that high-dose thromboprophylaxis has a similar composite of thrombotic events in critically ill patients with COVID-19 as intermediate-dose and standard-dose thromboprophylaxis regimens ( 29 , 31 , 32 ). In addition, parallel to observational and RCT studies ( 29 , 31 , 32 , 57 , 58 ), different thromboprophylaxis doses did not eliminate the risk of overall mortality. This cast doubt on other studies that show a superior survival rate with escalated doses ( 37 , 59 , 60 ).…”

Section: Discussionsupporting

confidence: 90%

“…A meta-analysis of 23 retrospective observational studies found a favorable mortality reduction with the escalated dose of prophylactic anticoagulant when compared to the standard dose (28). However, high quality evidence of metaanalyses and randomized controlled trials (RCTs) investigating the clinical outcomes of various prophylactic regimens in critically ill patients have revealed conflicting results (29)(30)(31)(32)(33). Generally, previous studies were notably limited by poor study designs (6,34), diversity of study populations (34)(35)(36)(37), small sample sizes (6,36,38), variations in treatment settings (ICU vs. non-ICU) (39), heterogeneity of thromboprophylaxis dosing regimen definition (40), and unadjusted pooled crude estimates (34).…”

Section: Introductionmentioning

confidence: 99%

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A comparison of three thromboprophylaxis regimens in critically ill COVID-19 patients: An analysis of real-world data

Alrashed

Cahusac

Mohzari

et al. 2022

Front. Cardiovasc. Med.

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IntroductionThrombotic complications of coronavirus disease 2019 (COVID-19) have received considerable attention. Although numerous conflicting findings have compared escalated thromboprophylaxis doses with a standard dose to prevent thrombosis, there is a paucity of literature comparing clinical outcomes in three different anticoagulation dosing regimens. Thus, we investigated the effectiveness and safety profiles of standard, intermediate, and high-anti-coagulation dosing strategies in COVID-19 critically ill patients.MethodologyThis retrospective multicenter cohort study of intensive care unit (ICU) patients from the period of April 2020 to August 2021 in four Saudi Arabian centers. Inclusion criteria were age ≥ 18 years, diagnosis with severe or critical COVID-19 infection, and receiving prophylactic anticoagulant dose within 24–48 h of ICU admission. The primary endpoint was a composite of thrombotic events, with mortality rate and minor or major bleeding serving as secondary endpoints. We applied survival analyses with a matching weights procedure to control for confounding variables in the three arms.ResultsA total of 811 patient records were reviewed, with 551 (standard-dose = 192, intermediate-dose = 180, and high-dose = 179) included in the analysis. After using weights matching, we found that the standard-dose group was not associated with an increase in the composite thrombotic events endpoint when compared to the intermediate-dose group {19.8 vs. 25%; adjusted hazard ratio (aHR) =1.46, [95% confidence of interval (CI), 0.94–2.26]} or when compared to high-dose group [19.8 vs. 24%; aHR = 1.22 (95% CI, 0.88–1.72)]. Also, there were no statistically significant differences in overall in-hospital mortality between the standard-dose and the intermediate-dose group [51 vs. 53.4%; aHR = 1.4 (95% CI, 0.88–2.33)] or standard-dose and high-dose group [51 vs. 61.1%; aHR = 1.3 (95% CI, 0.83–2.20)]. Moreover, the risk of major bleeding was comparable in all three groups [standard vs. intermediate: 4.8 vs. 2.8%; aHR = 0.8 (95% CI, 0.23–2.74); standard vs. high: 4.8 vs. 9%; aHR = 2.1 (95% CI, 0.79–5.80)]. However, intermediate-dose and high-dose were both associated with an increase in minor bleeding incidence with aHR = 2.9 (95% CI, 1.26–6.80) and aHR = 3.9 (95% CI, 1.73–8.76), respectively.ConclusionAmong COVID-19 patients admitted to the ICU, the three dosing regimens did not significantly affect the composite of thrombotic events and mortality. Compared with the standard-dose regimen, intermediate and high-dosing thromboprophylaxis were associated with a higher risk of minor but not major bleeding. Thus, these data recommend a standard dose as the preferred regimen.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A comparison of three thromboprophylaxis regimens in critically ill COVID-19 patients: An analysis of real-world data

Alrashed

Cahusac

Mohzari

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…Results from the available RCTs of the conventional antithrombotic agents have not yet led to definitive answers. In patients admitted to the intensive care unit (ICU), intermediate‐dose or full‐dose prophylactic anticoagulation did not lead to improvement in clinical outcomes 5–8 . Among patients hospitalized in medical wards, the results for heparin‐based regimens are promising, although some details are yet to be clarified.…”

Section: Introductionmentioning

confidence: 99%

“…In patients admitted to the intensive care unit (ICU), intermediate-dose or full-dose prophylactic anticoagulation did not lead to improvement in clinical outcomes. [5][6][7][8] Among patients hospitalized in medical wards, the results for heparin-based regimens are promising, although some details are yet to be clarified. Escalated-dose prophylaxis with rivaroxaban was not associated with improvement in outcomes.…”

Section: Introductionmentioning

confidence: 99%

Use of novel antithrombotic agents for COVID‐19: Systematic summary of ongoing randomized controlled trials

Talasaz

Sadeghipour

Aghakouchakzadeh

et al. 2021

Journal of Thrombosis and Haemostasis

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Background Coronavirus disease 2019 (COVID‐19) is associated with macro‐ and micro‐thromboses, which are triggered by endothelial cell activation, coagulopathy, and uncontrolled inflammatory response. Conventional antithrombotic agents are under assessment in dozens of randomized controlled trials (RCTs) in patients with COVID‐19, with preliminary results not demonstrating benefit in several studies. Objectives Given the possibility that more novel agents with antithrombotic effects may have a potential utility for management of patients with COVID‐19, we assessed ongoing RCTs including these agents with their potential mechanism of action in this population. Methods We searched clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to identify RCTs of novel antithrombotic agents in patients with COVID‐19. Results Based on a systematic literature search, 27 RCTs with 10 novel antithrombotic agents (including nafamostat, dociparstat, rNAPc2, and defibrotide) were identified. The results from these trials have not been disseminated yet. The studied drugs in the ongoing or completed RCTs include agents affecting the coagulation cascade, drugs affecting endothelial activation, and mixed acting agents. Their postulated antithrombotic mechanisms of action and their potential impact on patient management are summarized. Conclusion Some novel antithrombotic agents have pleiotropic anti‐inflammatory and antiviral effects, which may help reduce the viral load or fibrosis, and improve oxygenation. Results from ongoing RCTs will elucidate their actual role in the management of patients with COVID‐19.

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COVID-19-Associated Pulmonary Embolism: Review of the Pathophysiology, Epidemiology, Prevention, Diagnosis, and Treatment

Ortega‐Paz

Talasaz

Sadeghipour

et al. 2022

Semin Thromb Hemost

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COVID-19 is associated with endothelial activation in the setting of a potent inflammatory reaction and a hypercoagulable state. The end result of this thromboinflammatory state is an excess in thrombotic events, in particular venous thromboembolism. Pulmonary embolism (PE) has been of special interest in patients with COVID-19 given its association with respiratory deterioration, increased risk of intensive care unit admission, and prolonged hospital stay. The pathophysiology and clinical characteristics of COVID-19-associated PE may differ from the conventional non–COVID-19-associated PE. In addition to embolic events from deep vein thrombi, in situ pulmonary thrombosis, particularly in smaller vascular beds, may be relevant in patients with COVID-19. Appropriate prevention of thrombotic events in COVID-19 has therefore become of critical interest. Several changes in viral biology, vaccination, and treatment management during the pandemic may have resulted in changes in incidence trends. This review provides an overview of the pathophysiology, epidemiology, clinical characteristics, and risk factors of COVID-19-associated PE. Furthermore, we briefly summarize the results from randomized controlled trials of preventive antithrombotic therapies in COVID-19, focusing on their findings related to PE. We discuss the acute treatment of COVID-19-associated PE, which is substantially similar to the management of conventional non-COVID-19 PE. Ultimately, we comment on the current knowledge gaps in the evidence and the future directions in the treatment and follow-up of COVID-19-associated PE, including long-term management, and its possible association with long-COVID.

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Standard Prophylactic Versus Intermediate Dose Enoxaparin in Adults with Severe COVID-19: A Multi-Center, Open-Label, Randomised Controlled Trial

Cited by 6 publications

References 0 publications

A comparison of three thromboprophylaxis regimens in critically ill COVID-19 patients: An analysis of real-world data

A comparison of three thromboprophylaxis regimens in critically ill COVID-19 patients: An analysis of real-world data

Use of novel antithrombotic agents for COVID‐19: Systematic summary of ongoing randomized controlled trials

COVID-19-Associated Pulmonary Embolism: Review of the Pathophysiology, Epidemiology, Prevention, Diagnosis, and Treatment

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