(82) High-Intensity Thromboprohylaxis Is Not Associated with Reductions in COVID-19 Worsening, Severe Disease, or Death

Saturday, August 27, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 756

Presenting Author(s)

Corey S. Joseph
– JHSPH Center for Drug Safety & Effectiveness, Johns Hopkins University, Baltimore, Maryland, United States

Co-Author(s)

Kayte M. Andersen, MSc
– Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
Hemalkumar B. Mehta, PhD
– Assistant Professor, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States
Michael B. Streiff, MD
– Professor, Johns Hopkins University, Baltimore, MD, United States
Joshua Betz
– Johns Hopkins Bloomberg School of Public Health, United States
ROBERT C. BOLLINGER, MD, MPH
– Professor, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Arielle Fisher, PhD
– Sarah Cannon, Genospace, HCA Healthcare Research Institute, United States
Amita Gupta, MD, MHS
– Johns Hopkins University School of Medicine, United States
Charles F. LeMaistre, MD
– Physician in Chief Hematology, Sarah Cannon, Nashville, United States
Matthew Robinson, MD
– Johns Hopkins University School of Medicine, United States
Yanxun Xu
– Johns Hopkins University, United States
Derek K. Ng, PhD
– Assistant Professor, Department of Epidemiology, Johns Hopkins Blooomberg School of Public Health, United States
G. Caleb Alexander, MD
– Professor of Epidemiology and Medicine, JHSPH Center for Drug Safety & Effectiveness, Baltimore, Maryland, United States
Brian Garibaldi
– Associate Professor, Johns Hopkins University School of Medicine, MD, United States

Background: Current clinical guidelines recommend thromboprophylaxis for adults hospitalized with COVID-19, yet it is unknown whether higher doses offer benefits beyond standard doses. Moreover, the literature that forms the basis of these guidelines has not examined the effects of changes in intensity throughout the course of an inpatient stay. To date, studies have examined smaller datasets, and have not considered the time-varying exposures that might bias intention-to-treat analyses.

Objectives: To compare the real-world effectiveness of high-intensity versus standard thromboprophylaxis in preventing escalation to therapeutic anticoagulation, severe disease or death among adults hospitalized with COVID-19 in the US.

Methods: We studied electronic health records from 51,193 adults hospitalized with COVID-19 in the US between February 2020-February 2021. This period was before widespread vaccination and the propagation of the Delta variant. We defined time-varying exposure to standard (enoxaparin 30 or 40mg QD, fondaparinux 2.5mg, low dose apixaban or rivaroxaban, or heparin 5000u BID or TID) versus high-intensity (enoxaparin 30 or 40mg BID, or up to 1.2mg/kg of body weight QD, heparin 7500u TID, heparin 10,000u BID or TID, or dabigatran 220mg QD) thromboprophylaxis. We separately examined risk of escalation to therapeutic anticoagulation, severe disease (first occurrence of high-flow nasal cannula, non-invasive positive pressure ventilation or invasive mechanical ventilation), and death. To summarize risk, we present hazard ratios (HR) with 95% confidence intervals (CI) using Cox proportional hazards models incorporating time-varying treatment.

Results: Persons whose first dose was high intensity (n=14,224) were younger, more often obese and had greater oxygen support requirements than those who received standard thromboprophylaxis (n=36,969). Overall, 14% of persons changed from thromboprophylaxis to therapeutic anticoagulation, 18% progressed to severe disease and 11% died within 10 days of their last prophylactic dose. High-intensity thromboprophylaxis was associated with increased risk of therapeutic anticoagulation (HR 3.24, CI 3.08-3.41), severe disease (HR 1.22, CI 1.16-1.27) and death (HR 1.37, CI 1.21-1.55). Increased risks persisted in subgroup and sensitivity analyses varying populations and definitions of exposures, outcomes, and covariates.

Conclusions: Our findings do not support routine use of high-intensity thromboprophylaxis to prevent clinical worsening, severe disease or death among adults hospitalized with COVID-19.