Initiation of therapeutic anticoagulation within 2 days of intensive care unit (ICU) admission did not appear to affect survival in critically ill patients with coronavirus disease 2019 (COVID-19), according to the results of a target trial emulation as part of an observational study conducted by the network of researchers for the STOP-COVID investigation (ClinicalTrials.gov Identifier: NCT04343898). The findings were presented by Hanny Al-Samkari, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“Until data from randomized control trials are available, clinical care may be informed by robust estimates from observational data on the effect of therapeutic anticoagulation on clinical outcomes in COVID-19. This was the primary goal of the present study,” said Dr Al-Samkari.
In a multicenter cohort study conducted at 67 hospitals in the Unites States, investigators of the STOP-COVID network assessed the incidence of venous thromboembolism (VTE), major bleeding, and other coagulation-associated complications in critically ill patients with COVID-19 within 14 days of ICU admission and identified independent predictors of VTE upon ICU admission.
The investigators also conducted a target trial emulation, controlling for 22 baseline characteristics and disease covariates, to estimate the effect of therapeutic anticoagulation on 28-day survival with patients being assigned to receive or not receive therapeutic anticoagulation within 2 days of ICU admission (excluding patients previously receiving anticoagulation and those with major bleeding or thrombocytopenia).
Of the 3239 critically ill adults assessed, the median patient age was 61 years (interquartile range [IQR], 53-71); 64.5% of patients were men. On day 1 of ICU admission, 66% of patients were intubated, and vasopressors were initiated in 42% of patients. By day 14, therapeutic anticoagulation was initiated in 43.6% of patients. By day 28, 39.3% of patients had died, 43.4% of patients had been discharged alive, and 17.4% of patients remained hospitalized.
By day 14, 6.3% of patients had developed radiographically confirmed VTE; 2.8% of patients had a major bleeding event (66.7% occurred while on anticoagulation), 1.5% of patients experienced disseminated intravascular coagulation, and 0.6% of patients developed heparin-induced thrombocytopenia. Mortality in patients with VTE was 38.2%, which was similar to the rate in the whole cohort; however, mortality among patients with major bleeding events was 71.1%.
Independent predictors of VTE were male sex (odds ratio [OR], 1.70; 95% CI, 1.05-2.77), severe obesity (body mass index ≥40 vs <30; OR, 2.08; 95% CI, 1.17-3.70), and higher D-dimer values (>10,000 ng/mL vs ≤1000 ng/mL; OR, 4.20; 95% CI, 2.17-8.14).
In the target trial emulation (n=2809), 11.9% of patients received therapeutic anticoagulation within 2 days of ICU admission. The groups were considered well balanced for all 22 covariates after weighting. After a median follow-up of 27 days, no significant difference in risk of mortality was observed between patients who received therapeutic anticoagulation and those who did not (hazard ratio, 1.12; 95% CI, 0.92-1.35). This result was similar with different analyses and across subgroups.
“Our findings do not support empiric use of therapeutic anticoagulation in critically ill patients with COVID-19,” concluded Dr Al-Samkari.
Limitations of the study include the possibility of residual confounding and underestimation of VTE and bleeding.
Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Read more of Hematology Advisor’s coverage of the ASH 2020 meeting by visiting the conference page.
Al-Samkari H, Gupta S, Leaf RK, et al. Thrombosis, bleeding, and the effect of anticoagulation on survival in critically ill patients with COVID-19 in the United States. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 581.
This article originally appeared on Hematology Advisor