Evaluation of Bivalirudin Weight-Based Dosing in Obese Patients

Abstract

Objective: Bivalirudin is an intravenous direct thrombin inhibitor with weight-based dosing. Bivalirudin is typically dosed based on actual body weight, but the most appropriate dosing weight for obese patients is unclear. The purpose of this study was to determine whether bivalirudin dosing requirements differ between obese and non-obese patients, stratified by renal function. Methods: This multicenter retrospective cohort study was conducted at two academic medical centers and evaluated adult patients receiving bivalirudin from July 1, 2016-November 1, 2021. Patients were excluded if they met any of the following criteria: received bivalirudin in a procedural area only, intradermally (non-IV), or with prophylactic intention; required extracorporeal membrane oxygenation (ECMO), baseline aPTT above 40 seconds; or had missing data. For patients with multiple bivalirudin treatment episodes, only the first was included. Obesity was defined as body mass index > 30 kg/m2 as per World Health Organization criteria. A therapeutic activated partial thromboplastin time was defined according to the institutional standard of 50 to 65.9 seconds. Results: The bivalirudin dose resulting in the first therapeutic aPTT was not significantly different between obese patients and non-obese patients stratified by renal function. In the CrCl ≥ 60 mL/min cohort, obese patients required a median dose of 0.15 mg/kg/hr (IQR 0.13, 0.19) compared to 0.17 mg/kg/hr (IQR 0.14, 0.28) for non-obese patients, p=0.064. In the CrCl 30-59 mL/min cohort, obese patients required a median dose of 0.13 mg/kg/hr (IQR 0.08, 0.14) compared to 0.15 mg/kg/hr (IQR 0.12, 0.24) for non-obese patients, p=0.078. In the CrCl < 30 mL/min, iHD, or CVVHD cohort, obese patients required a median dose of 0.06 mg/kg/hr (IQR p75 0.03, 0.13) compared to 0.05 mg/kg/hr (IQR 0.03, 0.09) for non-obese patients, p=0.681). The time to first therapeutic aPTT on bivalirudin was significantly longer in non-obese patients (17.2 hrs) compared to obese patients (9 hrs) in the CrCl > 60 mL/min cohort (p=0.013). The time to first aPTT value above 50 seconds was also significantly longer in non-obese patients (16.9 hrs) compared to obese patients (6.4 hrs) in the CrCl ≥ 60 mL/min cohort (p<0.001). Conclusion: Bivalirudin doses resulting in the first therapeutic aPTT value were not significantly different between obese and non-obese patients regardless of renal function category, but there was a trend towards lower dosing requirements in obese patients with CrCl > 60 mL/min compared to non-obese patients in this category. The time to achievement of the first therapeutic aPTT value was significantly longer in non-obese patients with CrCl > 60 mL/min, and this population may benefit from a higher bivalirudin starting dose.