Introduction: Dosing of the renally eliminated direct thrombin inhibitor, bivalirudin, is typically based on the estimated glomerular filtration rate (eGFR) using creatinine, which is prone to inaccuracies in critically ill patients. The objective of this study was to characterize the performance of cystatin C on initial bivalirudin dose selection and the resultant anticoagulant effect.
Methods: This was a historical observational study of hospitalized patients with a concurrent cystatin C and creatinine assessment (within 24 hours of each other) prior to bivalirudin initiation. The CKD-EPI equation was used to calculate the eGFR using creatinine (eGFRCr) and cystatin C (eGFRCysC). Discordant eGFR was defined by eGFRCysC that was at least 15 ml/min lower than eGFRCr. The effect of varied eGFR methods on initial dose selection was assessed in simulation using traditional categorical thresholds of creatinine clearance for bivalirudin dose selection. The influence of discordant eGFR on the increase in activated partial thromboplastin time (aPTT) on first assessment was characterized.
Results: Of the 205 patients included, bivalirudin was most used for extracorporeal membrane oxygenation (n = 97; 47%) and treatment of venous thromboembolism (n = 72; 35%). The median (interquartile range) eGFRCysC was significantly lower than the eGFRCr (59 [33, 87] vs. 94 [54, 124] ml/min; p < 0.001), and GFR estimates were discordant in 132 (64%) patients. Had eGFRCysC been used in place of estimated creatinine clearance, initial bivalirudin doses would have been similar in 61% of cases (weighted Kappa 0.44, 95% CI 0.34-0.53). In case of different recommended doses, eGFRCysC would have resulted in lower initial bivalirudin doses 86% of the time. Patients with eGFR discordance had non-significantly higher absolute (+23 vs. +18 sec, p = 0.082) and relative (+76% vs. +61%, p = 0.10) increases in their first aPTT assessment after bivalirudin initiation compared to patients with concordant eGFR.
Conclusions: Routine use of cystatin C-based eGFR would lead to selection of lower initial bivalirudin doses than traditional creatinine-based dosing methods.
