Impact of pre-admission antithrombotic therapy on disease severity and mortality in patients hospitalized for COVID-19

Abstract

Anticoagulant therapy is a cornerstone treatment for coronavirus disease 2019 (COVID-19) due to the high rates of thromboembolic complications associated with this disease. We hypothesized that chronic antithrombotic therapy could play a protective role in patients hospitalized for COVID-19. Retrospective, observational study of all patients admitted to our hospital for ≥ 24 h from March 1 to May 31, 2020 with SARS-CoV-2. The objective was to evaluate clinical outcomes and mortality in COVID-19 patients receiving chronic anticoagulation (AC) or antiplatelet therapy (AP) prior to hospital admission. A total of 1612 patients were evaluated. The mean (standard deviation; SD) age was 66.5 (17.1) years. Patients were divided into three groups according to the use of antithrombotic therapy prior to admission (AP, AC, or no-antithrombotic treatment). At admission, 9.6% of the patients were taking anticoagulants and 19.1% antiplatelet therapy. The overall mortality rate was 19.3%. On the multivariate analysis there were no significant differences in mortality between the antithrombotic groups (AC or AP) and the no-antithrombotic group (control group). Patients on AC had lower ICU admission rates than the control group (OR: 0.41, 95% CI, 0.18–0.93). Anticoagulation therapy prior to hospitalization for COVID-19 was associated with lower ICU admission rates. However, there were no significant differences in mortality between the patients receiving chronic antithrombotic therapy and patients not taking antithrombotic medications. These findings suggest that chronic anticoagulation therapy at the time of COVID-19 infection may reduce disease severity and thus the need for ICU admission.

Association between pre‐admission anticoagulation and in‐hospital death, venous thromboembolism, and major bleeding among hospitalized COVID‐19 patients in Japan

“…Second, a lower incidence of VTE in this study compared to those in previous studies conducted in western countries may partly explain the result of in‐hospital mortality. In‐hospital mortality was reported to be 7.9%–15.6% in Japan 29,30 and 15.0%–43.8% in western countries 9–20 . A lower incidence of VTE has been reported in Japan, 30 which is in line with our result.…”

“…Notably, the incidence of VTE in this study was 0.4% (10/2612) for DVT and 0.3% (9/2612) for PE, and this is comparable to a previous study in Japan which reported an incidence proportion of 0.9% for DVT and 0.5% for PE 30 . On the other hand, the incidence proportion of VTE was lower compared to that of previous studies summarized in Table S2, which ranged from 1.2% to 6.8% 11,18,20 . This was also lower than that reported in a previous meta‐analysis, which mainly included the studies from Western countries (the pooled incidence proportions of PE and DVT were 16.5% and 14.8%, respectively) 31 .…”

“…One study reported an increased odds ratio of major or clinically relevant nonmajor bleeding among patients with COVID‐19 receiving therapeutic doses of anticoagulation treatment compared to those receiving prophylactic doses of anticoagulation treatment 21 . As shown in Table S2, several studies showed a higher incidence of bleeding events in patients with pre‐admission anticoagulation treatment than in those without pre‐treatment 11,16,19,20 . Given the conflicting data from previous studies, clinical practitioners need more information to decide whether pre‐admission anticoagulation treatment should be maintained or terminated.…”

Thrombotic and bleeding events, mortality, and anticoagulant use among 546,656 hospitalized patients with COVID-19 in the United States: a retrospective cohort study

“…Another RCT reported that intermediate-dose enoxaparin was not more effective in preventing death or thrombosis than standard-dose enoxaparin in hospitalized patients with COVID-19 [ 14 ], and the ACTION RCT found that anticoagulation with rivaroxaban or enoxaparin, followed by rivaroxaban for 30 days, did not improve clinical outcomes and led to increased bleeding when compared with prophylactic anticoagulation [ 15 ]. Observational studies have shown inadequate anticoagulation and limited benefit of prophylactic anticoagulation on mortality rates in patients with COVID-19 [ 16 – 19 ].…”

Potential antiviral properties of antiplatelet agents against SARS-CoV-2 infection: an in silico perspective

“…Recent data showed that anticoagulant therapy has better results in moderate and severe COVID-19 patients with coagulopathy signs and those receiving mechanical ventilation [ 12 , 16 ]. Additionally, the prophylactic impact of antithrombotic therapy on COVID-19 severity and mortality has been considered [ 17 ]. Moreover, it was reported that heparin could bind with the SARS-CoV-2 S1 receptor domain leading to a conformational change that hinders cell infection, which confirms the antiviral effect of heparin against COVID-19 [ 18 ].…”