Retrospective review of Andexanet Alfa versus 4-Factor Prothrombin Complex Concentrate for reversal of DOAC-Associated Intracranial Hemorrhage.

Background: Mortality of oral anticoagulation-associated ICH is around 60%, with oral anticoagulation increasing the risk of ICH seven to ten-fold compared to no anticoagulation. Current guidelines recommend DOACs (direct oral anticoagulants) as first-line therapy in the treatment of VTE (Venous Thromboembolism) due to their more favorable safety profile. There are two agents available for DOAC reversal, Coagulation Factor Xa (recombinant), inactivated-zhzo (andexanet alfa, Andexxa®) and 4-factor prothrombin complex concentrate (4FPCC). There is little data comparing the two agents in real-life clinical settings. OBJECTIVE: The primary objective of this study was to determine if there was a difference in hemostatic efficacy of andexanet alfa and 4FPCC in patients with a factor Xa inhibitor-related intracranial hemorrhage. METHODS: This was a retrospective, single-center study conducted in adult patients admitted at a quaternary academic medical center from September 2017 to March 2021. Adults with a diagnosis of intracranial hemorrhage (ICH) were included if they received either 4FPCC or andexanet alfa for reversal of apixaban or rivaroxaban. In addition to hemostatic efficacy per imaging, we assessed disposition location, cerebral performance score, blood product consumption, and the development of a new thrombus. RESULTS: A total of 46 patients were included in this study, 15 received 4FPCC (32%) and 31 received andexanet alfa (68%). There was no difference in the proportion of patients with excellent (4FPCC 9 [60%] vs. andexanet alfa 16 [51.6%], p = 0.61), good (4FPCC 2 [13.3%] vs. andexanet alfa 7 [22.6%]), or poor (4FPCC 1 [6.7%] vs. andexanet alfa 5 [16.1%]) hemostasis after administration of each agent. There were no significant differences in any secondary outcomes. CONCLUSION AND RELEVANCE: Our study found no difference in hemostatic efficacy between andexanet alfa and 4FPCC. At this time, clinicians should choose an agent based on individual patient presentation and resource availability. Further research will help clarify the role of each agent in the management of DOAC-related intracranial hemorrhage.

Evaluation of standard versus reduced dose apixaban for the treatment of venous thromboembolism in patients with severe renal disease (ESRD-VTE).

BACKGROUND: There are no clear dosing recommendations when using apixaban for venous thromboembolism (VTE) treatment in patients with severe or end-stage renal disease; clinical trials excluded patients with a creatinine clearance (CrCl) <25 mL/min or on dialysis. This study compares bleeding rates in patients with severe or end-stage renal disease taking standard versus reduced dose apixaban for VTE treatment. MATERIALS AND METHODS: This was a multicenter, retrospective cohort study using electronic medical records between January 1, 2013, and August 31, 2021. This study included patients 18 years or older who had severe or end-stage renal disease when prescribed apixaban for VTE treatment. Severe or end-stage renal disease was defined as at least one of the following: CrCl <25 mL/min, SCr >2.5 mg/dL, CKD stage 4 or 5, or on dialysis. The primary endpoint was rate of clinically relevant bleeding within six months of starting apixaban. Secondary endpoints were VTE recurrence within six months of starting apixaban, time to clinically relevant bleed, and time to VTE recurrence. RESULTS: A total of 203 patients were included in the final analysis (n = 125 on 5 mg; n = 78 on 2.5 mg). Clinically relevant bleeding rate was significantly higher in the standard dose group (14.4 % vs 3.8 %, p = 0.02). Rates of VTE recurrence appear similar (6.4 % vs 7.7 %, p = 0.21). CONCLUSIONS: A reduced dose of apixaban may be considered when treating VTE in patients with severe or end-stage renal disease.