Evaluation of clinical outcomes of 4-factor prothrombin complex concentrate versus andexanet alfa in the treatment of intracerebral hemorrhage

Purpose: Oral anticoagulants account for up to 20% of intracerebral hemorrhages (ICH) with one-year mortality estimated as high as 54%. Several studies have examined the use of 4-Factor prothrombin complex concentrate (4F-PCC) and andexanet alfa in the treatment of factor Xa associated ICH. High cost burden, lack of clinical outcomes, and risk of thromboembolic events continues to be a major dilemma behind product selection at many healthcare systems. The purpose of this project is to compare clinical outcomes between 4F-PCC and andexanet alfa in the management of patients with ICH secondary to apixaban and rivaroxaban at Baptist Hospital of Miami (BHM). Methodology: This single-center, performance improvement project was a retrospective chart review conducted for all patients admitted to BHM between August 1, 2018 and March 30, 2020. Patients were included if they received either 4F-PCC or andexanet alfa for the management of ICH induced by apixaban and rivaroxaban. The primary outcome of this project compared bleeding expansion at 24 and 48 hours among these two groups as defined by a brain computed tomography (CT) scan. Secondary outcomes included dose of reversal agent used, time to reversal agent administration in relation to the last direct oral anticoagulant (DOAC) dose, thromboembolic events within 30 days, hospital length of stay, mortality rate, and discharge status. Nominal data was presented as means and percentages. Baseline demographics and characteristics as well as primary and secondary outcomes were compared using the Fisher Exact test and Student’s T-test with p-values less than 0.05 considered statistically significant. Results: Overall, 62 patients were screened for inclusion and exclusion criteria. Of these, 19 patients were included and evaluated for primary and secondary outcomes. Eligible patients were divided into group I (andexanet alfa, n=7) and group II (4F-PCC, n=12). Several baseline demographics and patient characteristics were noted to be similar between these two groups, but not statistically significant. In reference to the primary outcome, patients in group I had 0% expansion of bleeds whereas group II patients had a 30% expansion of bleed, all non-surgical SDH (p=0.52). The average dose of 4F-PCC was 30 units/kg while 86% of the patients received low dose andexanet alfa. Administration of andexanet alfa and 4F-PCC in relation to the last DOAC dose was an average of 13 hours for both groups (p=0.91). The average hospital length of stay was 13 days for both groups (p=0.98). The incidence of thromboembolic events was noted to be 25% in group I while no thromboembolic events were noted in group II (p=0.26). Overall, there was a 14% mortality rate in group I versus 25% in group II (p=0.50). Conclusion: This study demonstrates clinical significant results relating to the efficacy and safety concerns of andexanet alfa and 4F-PCC in the management of ICH. As the results suggested, andexanet alfa treated patients had 0% expansion of bleed at 24 and 48 hours versus 30% in 4F-PCC treated patients (p=0.52), all non-surgical SDH. Moreover, the percent decrease in volume for the bleeding expansion was greater for andexanet alfa in the ICH arm, (52% vs 19%). Lastly, andexanet alfa treated patients had 0% thromboembolic rates versus 25% in 4F-PCC treated patients (p=0.26) with an overall mortality rate of 14% versus 25% respectively (p=0.50)