Anticoagulation Strategies in Non-Critically Ill Patients with Covid-19

Area of Science:

• Critical care medicine
• Infectious diseases
• Pharmacology

Background:

• Determining the optimal thromboprophylaxis strategy for hospitalized coronavirus disease 2019 (COVID-19) patients is crucial.
• Previous studies have yielded uncertain results regarding the most effective anticoagulation approach.

Purpose of the Study:

• To compare the effectiveness of different doses of low-molecular-weight heparin (LMWH) thromboprophylaxis, with or without aspirin, in hospitalized COVID-19 patients.
• To evaluate the impact of therapeutic-dose anticoagulation in this patient population.

Main Methods:

• An adaptive platform trial randomized 1574 hospitalized COVID-19 adults to low-dose LMWH, intermediate-dose LMWH, or low-dose LMWH plus aspirin.
• The aspirin arm was discontinued, and a therapeutic-dose arm was added based on emerging evidence.
• The primary endpoint was death or need for new organ support by day 28, analyzed using Bayesian logistic models.

Main Results:

• Among 1526 analyzed patients, the primary outcome occurred in 5.9% (low-dose), 4.2% (intermediate-dose), 7.2% (low-dose + aspirin), and 14% (therapeutic-dose).
• Compared to low-dose, intermediate-dose LMWH had an 86% posterior probability of reducing the primary outcome (OR 0.74, 95% CrI 0.43-1.27).
• Therapeutic-dose anticoagulation showed a 7% probability of benefit (OR 2.22, 95% CrI 0.77-6.20); overall thrombotic and bleeding rates were low (0.8% and 0.4%).

Conclusions:

• Intermediate-dose LMWH demonstrated an 86% probability of being more effective than low-dose thromboprophylaxis in non-critically ill hospitalized COVID-19 adults.
• Low-dose LMWH with aspirin showed a 65% probability of benefit, while therapeutic-dose anticoagulation had only a 7% probability of benefit.
• Trial closure due to operational constraints prevented definitive conclusions on optimal anticoagulation strategies for COVID-19 patients.