Thromboprophylaxis with Enoxaparin Reduces Mortality in Patients Hospitalized with COVID-19
Severe acute respiratory syndrome caused by COVID-19 is associated with a hypercoagulable state and an increased risk of thrombotic events. Since the beginning of the pandemic, thromboprophylaxis has been recommended for these patients despite initial insufficient evidence. In the fall of 2020, an observational study was published confirming the beneficial effect of enoxaparin on reducing mortality and the risk of ICU admission in patients with severe COVID-19.
Introduction
The hypercoagulable state in COVID-19 is likely caused by a combination of direct damage to endothelial cells infected by the virus and the release of pro-inflammatory cytokines. It is associated with an increased risk of deep vein thrombosis and pulmonary embolism, stroke, acute myocardial infarction, microvascular thrombosis, and acute arterial thrombosis.
In April 2020, the International Society on Thrombosis and Haemostasis (ISTH) issued recommendations that included thromboprophylaxis in patients with COVID-19. Given the lack of evidence from randomized studies, data from observational clinical evaluations are beneficial.
Study Population
Patients hospitalized at the Fondazione Poliambulanza Istituto Ospedaliero in Brescia, Italy, from February 20 to May 10, 2020, were included in the observational cohort study. Inclusion criteria included confirmed infection via RT-PCR and age over 18 years.
Patients who received at least one dose of enoxaparin during hospitalization (n = 799) were compared with those who did not receive enoxaparin (n = 604). The primary endpoint was in-hospital mortality, with secondary endpoints including the length of hospitalization and ICU admission.
The median dose of enoxaparin was 40 mg (40–80 mg), and the median duration of therapy was 6 days (3–9 days). Patients receiving enoxaparin were older on average (p = 0.01) and more often male (n = 545; p = 0.04). There was no statistically significant difference in the occurrence of comorbidities between the cohorts.
Results
Lower in-hospital mortality was observed in the enoxaparin cohort compared to the control cohort (odds ratio [OR] 0.53; 95% confidence interval [CI] 0.40–0.70). Mortality was comparable for patients with prophylactic and therapeutic doses of enoxaparin. However, for 194 patients with enoxaparin therapy shorter than 2 days, the reduction in mortality was not significant compared to the control group. Enoxaparin therapy was also associated with a lower risk of ICU admission (OR 0.48; 95% CI 0.32–0.69). Due to lower mortality, patients receiving enoxaparin had a longer hospitalization (incidence rate ratio [IRR] 1.45; 95% CI 1.36–1.54).
Conclusion
The study results indicate that administering enoxaparin to hospitalized COVID-19 patients reduces in-hospital mortality and the risk of ICU admission. Although these results need to be confirmed in randomized clinical trials, the cited observational study supports the recommended routine thromboprophylaxis for patients hospitalized with COVID-19.
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Source: Albani F., Sepe L., Fusina F. et al. Thromboprophylaxis with enoxaparin is associated with a lower death rate in patients hospitalized with SARS-CoV-2 infection. A cohort study. EClinicalMedicine 2020 Oct 5; 27: 100562, doi: 10.1016/j.eclinm.2020.100562.
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