Low-dose aspirin may reduce thromboembolic events associated with COVID-19, but not as much as when paired with the anticoagulant enoxaparin, according to a retrospective cohort study published in Clinical Drug Investigation.

The authors compared 225 patients with COVID-19 who had been treated with low-dose acetylsalicylic acid (ASA, aspirin) only, enoxaparin only, or low-dose ASA and enoxaparin. They also included a control group who did not receive ASA, other antiplatelet agents, other anticoagulants or enoxaparin.

An estimated 16% to 31% of patients with COVID-19 have thromboembolic events, particularly people with moderate to severe cases. Multiple studies have evaluated the role of low-dose ASA for COVID-19, but limited studies have evaluated the protective effects related to arterial thrombosis and risk of mechanical ventilation.

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Patients who received ASA, enoxaparin, or both were significantly older than patients who did not receive these medications. (P <.001). A total of 79.7% of patients who received enoxaparin alone, and 88.6% of patients who received both therapies had severe COVID-19. A total of 64.5% of patients who received ASA alone had moderate COVID-19.

Patients receiving ASA and enoxaparin had the lowest risk of thromboembolic events, with an odds ratio (OR) of 0.010 when compared to controls. Patients on enoxaparin alone had a lower OR than patients on ASA alone (0.071 vs 0.163), when compared to controls. Patients on both treatments were less likely to need mechanical ventilation than controls (OR, 0.032; P =.001) when adjusted for age and comorbidities.

The study results support the use of low-dose ASA, enoxaparin, or the combination of both to reduce the risk of thromboembolic events. Combination therapy led to the greatest reduction in events, as well as significant reduction in the need for mechanical ventilation.

Further randomized controlled trials are needed to better understand these results and causality. This study is limited by its observational designs, the small number of patients in each group and single institution. 

“Our focus as a community, at times, seems to be on the treatment of those most critically ill, often neglecting those who fall in limbo between recovery and hospitalization,” the authors wrote. “For this, we recommend the community consider the use of ASA for prevention of arterial and venous thrombotic events.”


Abdelwahab HW, Shaltout SW, Sayed Ahmed HA, et al. Acetylsalicylic acid compared with enoxaparin for the prevention of thrombosis and mechanical ventilation in COVID-19 patients: a retrospective cohort study. Clin Drug Investig. 2021;41(8):723-732. doi:10.1007/s40261-021-01061-2