P1563: remdesivir use in severe and critical covid-19 patients might be associated with lower incidence of arterial thrombotic events

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Remdesivir is the first drug to be approved for treatment of severe or critical COVID-19 patients, and subsequently for patients who do not require oxygen therapy but are at risk of severe COVID due to prior comorbidities. Venous and arterial thrombotic events are a striking feature of severe COVID-19, however, relationship of remdesivir use with the risk of thrombotic events is unknown and has not been investigated before. Aims: To evaluate occurrence of venous (VTE) and arterial thrombotic (AT) events among remdesivir treated and case-matched control hospitalized COVID-19 patients Methods: We retrospectively analyzed a cohort of 876 consecutive hospitalized COVID-19 patients who were treated with remdesivir and compared them to 876 case-matched control patients. All patients were treated in a tertiary level institution University hospital Dubrava, Zagreb, Croatia from 10/2020 to 6/2021. Control patients were chosen among 5083 patients from the institutional registry who were not exposed to remdesivir, and were 1:1 matched based on age, sex, Charlson comorbidity index, COVID severity at the time of hospital admission and the level of oxygen requirement at the time of remdesivir institution. Patients who experienced AT or VTE immediately prior or at the time of hospital admission were excluded from the analysis of cumulative incidence of particular thrombotic events. Myocardial infarction (MI), cerebrovascular infarction (CVI) and peripheral arterial thromboses were considered as AT. Deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE. All thromboses had to be proven by objective imaging and laboratory methods. Results: Median age was 66 years. Median Charlson comorbidity index was 3 points. A total of 61.8% of patients were of male sex, 80.2% had severe and 17.8% had critical severity of COVID-19 on admission. With the exclusion of 37 AT present at the time of hospital admission, there were a total of 38 AT events occurring during hospitalization (13 in the remdesivir and 25 in the control group), including 8 MI, 19 CVI and 11 peripheral AT events. Cumulative AT incidence occurring during hospitalization was 2.5% in entire cohort. Significantly lower cumulative incidence of arterial thrombotic events was observed among remdesivir than among matched control patients (1.7% vs 3.3%, HR=0.51, P=0.035), Figure panel A. With the exclusion of 71 VTE present at the time of hospital admission, there were a total of 70 VTE events occurring during hospitalization (35 in the remdesivir and 35 in the control group), including 34 DVT and 45 PE events. Cumulative VTE incidence occurring during hospitalization was 2.8% in an entire cohort. There was a similar cumulative incidence of VTE events among both remdesivir and matched control patients (P=0.287), Figure panel B. Summary/Conclusion: Remdesivir use in severe and critical COVID-19 patients might be associated with lower occurrence of arterial thrombotic events during hospitalization, whereas similar rates of venous thrombotic events were observed. Although mechanistically unclear at the moment, these effects might be attributed to similarity of main remdesivir metabolites to adenosine. Adenosine can cause vasodilatation and inhibition of platelet aggregation, mechanisms important in the pathogenesis of arterial thrombotic events. Future studies are warranted. Figure 1: Cumulative incidence of A) arterial and B) venous thrombotic events in remdesivir treated and matched control COVID-19 patients.Keywords: Arterial thrombosis, Coagulation, COVID-19