ABSTRACT
BACKGROUND: Since the outbreak of novel coronavirus SARS-CoV2 around the world, great attention has been paid to the effects of such antithrombotic drugs as heparinoids, because they have antiviral action in vitro and antithrombotic actions in vivo. We conducted a retrospective analysis in inpatients with confirmed COVID-19 on the anti-inflammatory and antithrombotic effects of enoxaparin and fondaparinux at prophylactic doses. METHODS: This retrospective cohort study used patients with confirmed COVID-19 during the first months of the Italian outbreak from February 18 to April 30, 2020. Our aim was to compare clinical characteristics, prophylactic treatment, markers of inflammation, and thrombotic outcomes in inpatients positive for SARS-CoV2 during hospitalization associated with thromboprophylaxis with enoxaparin (40 mg or 60 mg once daily) or fondaparinux (2.5 mg once daily). Statistical analysis was conducted with using MatLab R2016B and ad hoc functions. RESULTS: There were no significatant differences in clinical characteristics between patients that used enoxaparin or fondaparinux as thromboprophylaxis for SARS-CoV2. No differences were found in D-dimer and fibrinogen levels either, which were used as markers of inflammation during the infection at testing on admission and after 3 weeks.Significant differences in CRP, IL6, and LDH were found in patients after 21 days' treatment. DISCUSSION: Increased levels of fibrinogen and D-dimer in patients with confirmed COVID-19 have been reported in several studies. Our results showed that anti-inflammatory effects of fondaparinux and enoxaparin after 3 weeks of prophylactic treatment were similar when levels of fibrinogen and D-dimer were considered. Furthermore, levels of CRP showed a decrease in patients treated with enoxaparin and fondaparinux, although the decrease in the fondaparinux group seems to be more relevant.
ABSTRACT
Importance: The use of anticoagulant therapy with heparins decreased mortality in hospitalized patients with severe coronavirus disease 2019 (COVID-19). Even if enoxaparin and fondaparinux have the same clinical indication for venous thromboembolism (VTE) prevention; to date, there are no data about the use of fondaparinux in terms of safety, effectiveness, and impact on clinical prognosis among COVID-19 patients. Objective: To evaluate the safety, effectiveness, and clinical impact of VTE prophylaxis with fondaparinux and enoxaparin among COVID-19 patients hospitalized in internal medicine units. Design, Setting, and Participants: This was a retrospective multicenter observation study, including consecutive symptomatic patients with laboratory-proven COVID-19 admitted to internal medicine units of five Italian hospitals from 15th February to 15th March 2020. Main Outcomes and Measures: The primary safety outcome was the composite of major bleeding and clinically relevant non-major bleeding; the primary effectiveness outcome was the composite of all events classified as pulmonary embolism and deep venous thrombosis. The secondary effectiveness outcome included acute respiratory distress syndrome and all-cause death. Results: Among 120 COVID-19 patients enrolled in the study, 74 were taking enoxaparin (4,000 or 6,000 units/day) and 46 fondaparinux (2.5 units/day). No statistically significant difference in demographic and laboratory and clinical characteristics between the two groups has been shown. During a median follow-up of 32 (interquartile range: 14-51) days, the cumulative incidence rates of VTE and bleeding events on pharmacological thromboprophylaxis with heparins were 19% and 8%, respectively. The incidence of both VTE (6.5 vs. 13.5%; P = 0.36) and bleeding events (6.5 vs. 4.1%; P = 0.68) did not show a significant difference between COVID-19 patients on fondaparinux compared with those on enoxaparin therapy. The regression model for the risk of outcome events according to different VTE prophylaxis drugs did not show significant differences. Conclusions and Relevance: Although these results need confirmation by prospective studies including a larger population, our study provides preliminary evidence of a safe and efficacy use of fondaparinux for VTE prophylaxis in hospitalized COVID-19 patients.
ABSTRACT
The use of heparin has been shown to decrease the mortality in hospitalized patients with severe COVID-19. The aim of our study was to evaluate the clinical impact of venous thromboembolism prophylaxis with fondaparinux versus enoxaparin among 100 hospitalized COVID-19 patients. The incidence of pulmonary embolism, deep venous thrombosis, major bleeding (MB), clinically relevant non-MB, acute respiratory distress syndrome, and in-hospital mortality was compared between patients on fondaparinux versus enoxaparin therapy. The 2 groups were homogeneous for demographic, laboratory, and clinical characteristics. In a median follow-up of 28 (IQR: 12-45) days, no statistically significant difference in venous thromboembolism (14.5% vs. 5.3%; P = 0.20), MB and clinically relevant non-MB (3.2% vs. 5.3%, P = 0.76), ARDS (17.7% vs. 15.8%; P = 0.83), and in-hospital mortality (9.7% vs. 10.5%; P = 0.97) has been shown between the enoxaparin group versus the fondaparinux group. Our preliminary results support the hypothesis of a safe and effective use of fondaparinux among patients with COVID-19 hospitalized in internal medicine units.