FXa inhibitors (Nanjing ChinRily Medica)

Two hemostatic agents are commonly used to reverse factor Xa (fXa) inhibitor-related intracranial hemorrhage (ICH): andexanet alfa (AA) or 4-factor prothrombin complex concentrate (4F-PCC). We sought evaluate real-world data in Veterans diagnosed with fXa inhibitor-related ICH by comparing short-term mortality and thrombotic events in patients who received AA vs. 4F-PCC.

This was a national retrospective cohort from the Veteran Health Administration of AA or 4 F-PCC between January 2018 to January 2024.The primary effectiveness endpoint was 90-day mortality. The primary safety endpoint was 30-day thrombotic events (venous thromboembolism, pulmonary embolism, acute ischemic stroke [AIS], myocardial infarction), validated through manual chart review. Propensity score-matched data set was first created to balance AA and 4F-PCC by the significant demographic and clinical variables and then was used to analyze and compare the results using the complete data set.

Of 19,015 Veterans with ICH, 664 Veterans received AA (n = 151) or 4F-PCC (n = 513) and 350 Veterans received a fXa inhibitor (AA n = 129; 4F-PCC n = 221). 123 matched subjects were included in the propensity-matched cohort. The AA group was more likely to be on apixaban (AA group 87.8 % vs. 4F-PCC group 77.2 %, p = 0.03). There was no difference in 90-day mortality between groups (30.9 % vs. 36.6 %, p = 0.35). The AA group experienced significantly more 30-day thrombotic events compared to 4F-PCC (11.4 % vs. 2.4 %, p < 0.01) and AIS was significantly more common with AA.

In Veterans with fXa inhibitor-related ICH receiving AA or 4F-PCC, there was no difference in 90-day mortality. Consistent with previous literature from non-Veterans studies, 30-day thrombotic events were significantly higher in Veterans who received AA, including a significant increase in AIS. This study adds to the growing body of literature demonstrating higher thrombotic risks with AA. Selection of AA should be carefully weighed against the risk of thrombotic events.

Heterotopic ossification (HO) is a common complication following hip arthroplasty that can limit hip range of motion. Oral direct factor Xa (FXa) inhibitors are commonly used anticoagulants after arthroplasty; however, they have a high risk of local bleeding and hematoma formation, which are significant triggers for HO formation. To our knowledge, there is no evidence regarding whether FXa inhibitors use will increase HO incidence following hip arthroplasty.

In this retrospective propensity score-matched cohort study conducted at a national orthopaedic center in Shanghai (2019-2023), 944 patients undergoing hip arthroplasty for acute femoral neck fracture were evaluated. After exclusions and 1:1 matching (sex, age, body mass index, injury side, nonsteroidal anti-inflammatory drugs use), 362 patients were included in each group (FXa inhibitors vs. no FXa inhibitors). All patients received low-molecular-weight heparin during hospitalization and no other anticoagulants.

In the propensity score-matched population, the incidence of HO was 29.2% in the FXa inhibitors group and 15.7% in the no-FXa inhibitors group (7.7% and 2.4% for clinically important HO, respectively). Logistic regression analyses revealed that FXa inhibitors usage was significantly associated with a higher rate of HO (odds ratio, 2.22; 95% confidence interval, 1.55 to 3.20; P < 0.001) compared to no usage. Additionally, FXa inhibitors use was also linked to an increased risk of clinically significant HO (odds ratio, 3.29; 95% confidence interval, 1.59 to 7.48; P = 0.002). None of the baseline covariates demonstrated a significant influence on the association between FXa inhibitors use and HO incidence (P > 0.05 for all). Sensitivity analyses further corroborated these results.

Direct FXa inhibitors use may be a new risk factor of HO development following hip arthroplasty for acute femoral neck fracture.

Therapeutic Level II.