Acetylsalicylic Acid Compared with Enoxaparin for the Prevention of Thrombosis and Mechanical Ventilation in COVID-19 Patients: A Retrospective Cohort Study

Abstract

Background and Objective Low-dose acetylsalicylic acid (ASA, aspirin) is a well-known and frequently studied drug for primary and secondary prevention of disease due to its anti-inflammatory and coagulopathic effects. COVID-19 complications are attributed to the role of thrombo-inflammation. Studies regarding the use of low-dose ASA in COVID-19 are limited. For this reason, we propose that the use of low-dose ASA may have protective effects in COVID-19-related thromboembolism and lung injury. This study was conducted to assess the efficacy of low-dose ASA compared with enoxaparin, an anticoagulant, for the prevention of thrombosis and mechanical ventilation. Methods We conducted a retrospective cohort study on COVID-19-confirmed hospitalized patients at the Mansoura University Quarantine Hospital, outpatients, and home-isolated patients from September to December 2020 in Mansoura governorate, Egypt. Binary logistic regression analysis was used to assess the effect of ASA compared with enoxaparin on thromboembolism, and mechanical ventilation needs. Results This study included 225 COVID-19 patients. Use of ASA-only (81-162 mg orally daily) was significantly associated with reduced thromboembolism (OR 0.163, p = 0.020), but both low-dose ASA and enoxaparin, and enoxaparin-only (0.5 mg/kg subcutaneously (SC) daily as prophylactic dose or 1 mg/kg SC every 12 hours as therapeutic dose) were more protective (odds ratio [OR] 0.010, OR 0.071, respectively, p < 0.001). Neither ASA-only nor enoxaparin-only were associated with a reduction in mechanical ventilation needs. Concomitant use of low-dose ASA and enoxaparin was associated with reduced mechanical ventilation (OR 0.032, 95% CI 0.004-0.226, p = 0.001). Conclusions Low-dose ASA-only use may reduce the incidence of COVID-19-associated thromboembolism, but the reduction may be less than that of enoxaparin-only, and both ASA and enoxaparin. Concomitant use of ASA and enoxaparin demonstrates promising results with regard to the reduction of thrombotic events, and mechanical ventilation needs.

Clinical update on COVID-19 for the emergency and critical care clinician: Medical management

“…Recent data suggest that aspirin use is associated with improved COVID-19 patient outcomes, including decreased risk of thromboembolism, mechanical ventilation, ICU admission, and mortality [ [90] , [91] , [92] , [93] , [94] , [95] , [96] ]. Aspirin has been proposed to act on the intracellular signaling pathway involved with viral replication and reduction in systemic inflammation, cytokine release, platelet activity, and hypercoagulability.…”

“…Most patients received aspirin 81 mg daily. A single retrospective cohort study evaluated confirmed COVID-19 patients divided into four treatment groups: control (who did not receive aspirin, enoxaparin, or other antiplatelet or anticoagulation agents), aspirin alone, enoxaparin alone, or concomitant use of aspirin and enoxaparin [ 91 ]. Aspirin use included dosing of 81–162 mg daily within 7 days prior to or within 24 h following COVID-19 diagnosis.…”

“…Odds of VTE compared to control were significantly lower in those on aspirin alone (OR 0.163, 95% CI 0.035 to 0.752), but were even lower in enoxaparin alone (OR 0.071, 95% CI 0.018 to 0.280), or simultaneous aspirin and enoxaparin use (OR 0.010, 95% CI 0.001 to 0.078). Need for mechanical ventilation was reduced in only the combination group compared to control (OR 0.032, 95% CI 0.004 to 0.226) [ 91 ]. A study of patients on aspirin prior to COVID-19 found a decrease in overall mortality at 14 days (35,370 patients, OR 0.38, 95% CI 0.32 to 0.46) and 30 days (32,836 patients, OR 0.38, 95% CI 0.33 to 0.45) [ 92 ].…”

Aspirin in COVID-19: Pros and Cons

“…Another retrospective trial conducted in Egypt by Abdelwahab et al found that the risk of stroke or MI among patients on chronic aspirin therapy was significantly lower than among non-users after adjustment ( p = 0.02), but anticoagulants were found to be even more effective (adjusted OR = 0.071, p < 0.001) ( Abdelwahabet al, 2021 ). The essence of coagulopathy in COVID-19 is indeed hypothesized to be massive fibrin formation.…”

“…Antiplatelets were not found to affect the need for or time to mechanical ventilation, nor the risk of acute respiratory distress syndrome (ARDS) upon admission among patients on aspirin or other anti-platelets (taken as primary or secondary cardiovascular prophylaxis or as treatment for thromboembolic disease) ( Pan et al, 2019 ; Russo et al, 2020 ; Tremblay et al, 2020 ; Abdelwahab et al, 2021 ; Banik et al, 2021 ). Limitations within these studies include failure to adjust for smoking status and BMI, small sample size ( Abdelwahab et al, 2021 ), inclusion of only inpatients ( Abdelwahab et al, 2021 ), and lack of correction for the influence of post-admission treatments ( Tremblay et al, 2020 ). Banik et al were able to detect a positive effect of anti-coagulants on mechanical ventilation need but found no correlation between antiplatelets and intubation ( Banik et al, 2021 ).…”