Efficacy of Bivalirudin for Therapeutic Anticoagulation in COVID-19 Patients Requiring ECMO Support

Abstract

OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) pandemic has been associated with cases of refractory acute respiratory distress syndrome (ARDS) sometimes requiring support with extracorporeal membrane oxygenation (ECMO). Bivalirudin can be used for anticoagulation in patients on ECMO support, but its efficacy and safety in patients with COVID-19 is unknown. The authors set out to compare the pharmacologic characteristics and dosing requirements of bivalirudin in patients requiring ECMO support for ARDS due to COVID-19 versus ARDS from other etiologies. DESIGN AND SETTING: This retrospective case-control study was performed at Indiana University Health Methodist Hospital in Indianapolis, Indiana. PARTICIPANTS: Patients were included if they were on venovenous ECMO support between June 2019 and June 2020, and divided into two groups: ARDS secondary to COVID-19 and those with ARDS from another etiology (Non-COVID). INTERVENTIONS: Patient demographics, such as age, sex, weight, chronic comorbid conditions, baseline antiplatelet and anticoagulant use, antiplatelet use during ECMO, and need for renal replacement therapy were collected, and compared between groups. Time to activated partial thromboplastin time (aPTT) goal, percentage of time at aPTT goal, bivalirudin rates, total bivalirudin requirements, total duration on bivalirudin, total duration on ECMO, mortality, and complications associated with ECMO were collected and compared between groups. MEASUREMENTS AND MAIN RESULTS: A total of 42 patients met inclusion criteria (n = 19 COVID-19, n = 23 non-COVID). However, percentages of aPTTs at goal were maintained more consistently in patients with COVID-19 versus non-COVID (86% v 74%: p < 0.01). Higher median (IQR) daily rates (3.1 μg/kg/min [2.3-5.2] v 2.4 μg/kg/min [1.7-3.3]: p = 0.05) and higher median (IQR) maximum rates of bivalirudin (5 μg/kg/min [3.7-7.5] v 3.8 μg/kg/min [2.5-5]: p = 0.03) were required in the COVID-19 group versus the non-COVID group. Time to goal aPTT was similar between groups. There were no differences in complications associated with anticoagulation, as demonstrated by similar rates of bleeding and thrombosis between both groups. CONCLUSIONS: Patients on ECMO with ARDS from COVID-19 require more bivalirudin overall and higher rates of bivalirudin to maintain goal aPTTs compared with patients without COVID-19. However, COVID-19 patients more consistently maintain goal aPTT. Future randomized trials are needed to support efficacy and safety of bivalirudin for anticoagulation of COVID-19 patients on ECMO.