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Clinical Question
What dose of anticoagulation provides the most benefit for patients hospitalized with hypoxemic COVID-19 pneumonia?
Bottom line
In this study of mostly critically ill patients with hypoxemic COVID-19 pneumonia and no evidence of pulmonary embolus, neither high-dose prophylactic anticoagulation nor therapeutic anticoagulation led to a mortality benefit when compared with standard-dose prophylaxis. However, high-dose prophylaxis did provide a net efficacy and safety benefit over standard-dose anticoagulation by reducing de novo thrombosis by four-fold without increasing the rate of major bleeding. Therapeutic anticoagulation did not provide any additional benefit over high-dose prophylaxis. 1b
Reference
Study design: Randomized controlled trial (nonblinded)
Funding: Industry
Setting: Inpatient (any location)
Synopsis
Anticoagulation in patients hospitalized with a COVID-19 infection has been studied in different populations looking at different outcomes with varying results. In this study from France, adult patients hospitalized with COVID-19 pneumonia who required supplemental oxygen and had no evidence of pulmonary embolus on chest computer tomography were randomized to 3 distinct anticoagulation strategies using low-molecular-weight heparin (LMWH): standard-dose prophylaxis (n = 116), high-dose prophylaxis (n = 111), or therapeutic anticoagulation (n = 112). Exclusion criteria included severe renal disease and weight less than 40 kg or more than 100 kg. The preferred LMWH was tinzaparin, if available, and the high dose was twice that of the standard dose. The treatment was continued for 14 days, or until either hospital discharge or weaning off of supplemental oxygen for 48 hours. Of the 334 patients included in the intention-to-treat analysis, mean age was 58 years and 68% were men. No data on race and ethnicity were collected. Baseline characteristics, including comorbidities and Sepsis-related Organ Failure Assessment scores, were similar, and 90% of study patients required admission to the intensive care unit. The ranked composite primary outcome was all-cause mortality, followed by time to clinical improvement at day 28. The secondary outcome was the net clinical outcome for efficacy and safety defined as a composite of de novo thrombosis, major bleeding, or all-cause death at day 28. Overall, for the primary outcome, there was no difference in the probability of a more favorable outcome when comparing high dose to standard dose, therapeutic dose to standard dose, or therapeutic dose to high dose. However, for the secondary outcome of net clinical outcome, high dose fared better when compared with standard dose (16% vs 30%; P = .02), driven by a significant reduction in thrombosis without an increase in major bleeding.
Reviewer
Nita Shrikant Kulkarni, MD
Assistant Professor in Hospital Medicine
Northwestern University
Chicago, IL
Comments
Impact assessment
Excellent
Reference to usual vs 2x
A resident who was uncertain of the usual dose and any maximums brought this to my attention. Being explicit for a dose of tinzaparin would be helpful for those who are less familiar. Great choice of article - changes what we do.
covid pneumonia
high dose anticoag therapy reduces clots