Economic Evaluation of Andexanet Versus Prothrombin Complex Concentrate for Reversal of Factor Xa-Associated Intracranial Hemorrhage

Background and Purpose: Andexanet was approved by the Food and Drug Administration in 2018 for reversal of life-threatening or uncontrolled bleeding associated with factor Xa anticoagulation; however, the cost-effectiveness of Andexanet compared with standard of care (ie, prothrombin complex concentrate, PCC) in patients with factor Xa-associated intracranial hemorrhage (ICrH) is unknown. Methods: Cost-effectiveness analysis using a Markov cohort decision analytic model with a lifetime horizon was completed to determine the costs and benefits of Andexanet compared with PCC for reversal of factor Xa-associated ICrH. The population of interest was patients living in Canada on chronic factor Xa inhibitors for prevention of ischemic stroke in nonvalvular atrial fibrillation or the prevention/treatment of venous thromboembolism, presenting with an ICrH. Outcomes of interest were life expectancy (measured in years), quality-adjusted life years (QALY), costs (reported in 2020 Canadian dollars), and the incremental cost-effectiveness ratio. Results: An overall reduction in fatal ICrH and increase in thromboembolic events was associated with Andexanet compared with PCC. Andexanet had the highest discounted life expectancy of 2.53 years and a discounted QALY of 1.55. PCC had a discounted life expectancy of 2.09 years and a discounted QALY of 1.28. The average discounted lifetime costs were $237 177 Canadian dollars for Andexanet and $177 871 Canadian dollars for PCC. The strategy of Andexanet had an incremental cost-effectiveness ratio was $219 652 per QALY gained compared with the comparator of PCC. The probabilistic sensitivity analyses demonstrated that Andexanet (at its current cost) was cost-effective in 19% of simulations using a willingness-to-pay threshold of $50 000/QALY and 33% of simulations at $150 000/QALY. A 1-way sensitivity analysis found that for the incremental cost-effectiveness ratio to be <$150 000/QALY gained, Andexanet high or standard dosing would require a price reduction to <$24 000 Canadian (at current baseline efficacy). Conclusions: Based on available evidence, Andexanet represents low value for reversal of factor Xa-associated ICrH; however, there is substantial uncertainty reflecting the currently available data. Further comparative evidence and costing data will become available in the future with randomized trials of Andexanet versus PCC.

Automated summary

In patients with factor Xa-associated intracranial hemorrhage, Andexanet has shown to have a higher cost-effectiveness ratio compared to PCC. The use of Andexanet can reduce fatal ICrH and increase thromboembolic events.