Evaluating the effectiveness of a bivalirudin titration protocol in achieving therapeutic anticoagulation levels

Objectives: Bivalirudin has been evaluated in retrospective studies for indications outside of the setting of percutaneous intervention (PCI). Titration guidelines for non-PCI use are unavailable at this time, therefore, in 2008, this institution implemented a dosing protocol for bivalirudin. We hypothesized that the use of a standardized protocol would lead to a more rapid achievement and improved maintenance of therapeutic levels. 

Methods: A retrospective chart analysis was conducted for patients who received bivalirudin prior to implementation of the protocol (PP) (January 2005-March 2008) and after implementation (AP) (April 2008-June 2010). The bivalirudin dosing protocol is as follows: for aPTT <30 sec, increase by 50%; for aPTT 31-46 sec, increase by 25%; for aPTT 47-76 sec, no change; for aPTT 77-100 sec, decrease by 25%.  The aPTTs are monitored every 2 hours.  Patients were included in the study if they were ≥18 years of age and received bivalirudin for ≥24 hours. Subjects were excluded if bivalirudin was prescribed for PCI or perioperative use. Data collected included: time to first therapeutic aPTT, aPTTs at 24 and 48 hours, and bleeding episodes.

Results: Fifty-nine patients were evaluated. The average initial dose in the PP group (n=16) was 0.10±0.12 mg/kg/hr vs. 0.08±0.10 mg/kg/hr in the AP group (n=43) (p=0.29). The AP group reached therapeutic aPTTs 2.3 hours sooner than the PP group (10.23±26.7 hr and 7.99±22.0 hr) (p=0.30). Although both groups were therapeutic at 24 hours, only the AP group was therapeutic at 48 hrs (83.7% of AP group vs. 43.8% PP group; p=0.004). More bleeding was documented for the PP group compared to the AP group (25% vs. 16.3%; p=0.44).

Conclusion: Utilization of a standardized titration protocol for bivalirudin may lead to more rapid achievement of therapeutic levels and leads to persistent attainment of goal aPTTs.