Utility of CRCA™ P&T Highlighted in ASHP Presentation on Reversal Agent Safety & Efficacy

In our first collaborative research project, Agilum Healthcare Intelligence’s Clinical Solutions team and the Agilum Fellowship in Health Analytics and Artificial Intelligence (AI) at LIU Pharmacy are excited to share our preliminary findings recently presented at the 2021 American Society of Health-System Pharmacists Midyear Clinical Meeting. 

In just over three months, our research team developed and executed a project using Agilum’s Comparative Rapid Cycle Analytics P&T (CRCA™ P&T) platform to evaluate an important clinical question and report on critical outcomes, including hospital length of stay, readmission rate, and patient safety. 

This project leveraged Agilum’s analytics solution to assess differences in effectiveness and safety of four-factor prothrombin complex concentrate (4F-PCC), andexanet alfa, and idarucizumab to manage severe bleeding in patients on direct-acting oral anticoagulants (DOACs). 

The problem

Although clear advantages exist for using DOACs, all anticoagulants have an inherent risk of serious, sometimes fatal, bleeding events. Reversal agents like 4FPCC, andexanet alfa, and idarucizumab can all be used to help manage DOAC-associated severe bleeding events.

Of these three agents, andexanet alfa and idarucizumab were developed to reverse the effects of DOACs, but are associated with a higher cost, thereby creating a financial burden for many hospitals. In contrast, 4F-PCC is a commonly used alternative associated with lower cost.

How does 4F-PCC compare with andexanet alfa or idarucizumab for managing bleeding due to DOACs? Previous smaller studies have asked this question, but more extensive evaluations are needed to confirm clinically relevant outcomes between these reversal options. The most extensive study to date was a 2021 meta-analysis by Gómez-Outes et al. consisting of approximately 4,700 patients. 

Our findings

In contrast, we analyzed more than 7,000 clinical encounters documented from January 2019 through September 2021 captured by CRCA™ P&T. Our findings suggest similar outcomes to previous studies among the three reversal agents for the average length of stay (4F-PCC, 6 days [IQR 3-11]; andexanet alfa, 6 days [IQR 3-10]; idarucizumab, 5 days [IQR 3-9]; p=0.94) and 30-day all-cause readmission rates (4F-PCC, 11.4%; andexanet alfa, 10.7%; idarucizumab, 7.8%; p=0.42). These findings were consistent across subgroups of patients with documented intracranial or extracranial bleeding. 

We also noted differences in safety outcomes, with higher rates of deep vein thrombosis (4F-PCC, 4.7%; andexanet alfa, 7.9%; idarucizumab, 2.3%; p=0.04) and ischemic stroke (4F-PCC, 3.9%; andexanet alfa, 7.9%; idarucizumab, 3.9%; p=0.01) reported in patients receiving andexanet alfa, highlighting the need for careful selection and monitoring of patients.

Beyond these findings, this project showcased the utility of an innovative and robust analytics engine (Agilum’s CRCA P&T platform, in this case) to provide meaningful insights into real-world clinical outcomes supporting the use of 4F-PCC as an affordable alternative to idarucizumab or andexanet alfa. 

This is the first of many collaborative projects involving Agilum’s Clinical Solutions and Data Science and Quality teams and the Agilum Fellowship in Health Analytics and AI at LIU Pharmacy, and we look forward to sharing future progress and results. The Leonardi Institute’s innovative analytics fellowship program was established in June 2021.

2021 ASHP MCM Reversal Agents Poster