OBJECTIVES: Factor Xa (FXa) inhibitors such as rivaroxaban and apixaban, commonly used for the prevention of thrombosis, are associated with an increased risk of major, potentially life-threatening bleeding. Andexanet alfa (AA) is indicated to reverse the anticoagulation effects of rivaroxaban or apixaban in such bleeding events. The EMA authorized AA for use throughout the EU in 2019, although cost-effectiveness data are scarce. The objective of this analysis was to assess the cost-effectiveness of AA, from a Dutch perspective.

METHODS: A decision analytic model was used, comprising a decision tree in the short term and a Markov model in the long term. AA was compared to 4-factor prothrombin complex concentrate (4F-PCC) across rivaroxaban/apixaban users with life-threatening gastrointestinal, intracranial (ICH), or other major bleeds. The model was informed by the ANNEXA-4/ORANGE propensity score–matched comparison for 30-day mortality and by the ANNEXA-4/RETRACE indirect comparison for functional outcomes (for ICH). A lifetime horizon was applied, and a societal perspective was taken. Scenario analyses, including a healthcare perspective, were performed as well as one-way and probabilistic sensitivity analyses. Utility inputs and costs were sourced from literature and national list prices. Costs were inflated to 2023.

RESULTS: Treatment with AA was associated with a QALY gain of 1.099 and incremental costs of €31,195, resulting in an ICER of €28,385/QALY. Under a willingness to pay threshold of €50,000/QALY, AA had an 87% probability of being cost-effective. Assuming a healthcare perspective resulted in an ICER of €29,929/QALY. Although results were most sensitive to long-term costs and utilities post-ICH, results were generally consistent across sensitivity and scenario analyses.

CONCLUSIONS: While awaiting clinical trial (ANNEXA-I) results to confirm the incremental effectiveness of AA, this analysis indicates that AA is likely to be a cost-effective treatment option in patients with FXa inhibitor–related major bleeds in the Netherlands.