Andexanet Alfa Research Articles

Reversal agents for severe bleeding associated with direct oral anticoagulants

Direct oral anticoagulants (DOACs) have demonstrated a positive benefit-risk balance compared with vitamin K antagonists in both clinical trials and real-world studies. However, with increased DOAC use, the risk of bleeding should not be underestimated. In clinical practice, the annual rate of DOAC-related major bleeding is between approximately 1.5% and 3.5%. The outcome of major bleeds was similar or better in patients receiving DOACs than in those taking vitamin K antagonists. Due to their short half-lives, supportive measures are sufficient to manage most bleeds in patients receiving DOACs. Anticoagulant reversal should only be considered with life-threatening bleeds or with serious bleeds that fail to respond to usual measures. Effective strategies to reverse the anticoagulant effects of DOACs are now available. Idarucizumab has been approved for dabigatran reversal and andexanet alfa was recently granted approval for the reversal of apixaban or rivaroxaban in patients with life-threatening or uncontrolled bleeding events. Other reversal agents (e.g. ciraparantag for heparins and DOACs) are under development. Non-specific prohemostatic agents (e.g. prothrombin complex concentrate) can counteract the anticoagulant action of DOACs in emergency situations, when specific reversal agents are unavailable. However, specific reversal agents are efficacious and safe and should be preferred when available.

55 Andexanet Alfa Is Associated With Reduced In-hospital Mortality Compared to 4-Factor Prothrombin Complex Concentrate Among Patients With Intracranial or Gastrointestinal Bleeding

There are limited data on real-world effectiveness of the specific factor Xa (FXa) inhibitor reversal agent andexanet alfa (AA) in comparison with 4-factor prothrombin complex concentrates (4F-PCC). We compared in-hospital mortality in patients hospitalized with oral FXa inhibitor- or enoxaparin- related intracranial hemorrhage (ICH) or gastrointestinal (GI) bleeds who were treated with AA or 4F-PCC.

Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures.

Outcomes following andexanet alfa reversal of factor Xa inhibitors in patients requiring urgent or emergent invasive procedures are lacking. This study aimed to describe efficacy and safety outcomes following andexanet alfa administration within 24h of an invasive procedure. This single-center, observational, retrospective study included patients who received andexanet alfa within 24h of an invasive or surgical procedure. The primary outcome was hemostatic efficacy graded as excellent, good, or poor using similar definitions to the ANNEXA-4 criteria. Secondary outcomes included hospital discharge disposition, intensive care unit (ICU) and hospital length of stay, 30-day mortality, 30-day thromboischemic event rates, and serum coagulation assay changes pre- and postreversal. Forty-four patients met inclusion criteria; of these, 27 (62.8%) received apixaban and 16 (37.2%) were treated with rivaroxaban prior to admission. The indications for reversal were categorized as intracranial (n=20 [45.5%]) or extracranial (n=24 [54.5%]) sites. Majority of patients required emergent operative procedures (18 [40.9%]), followed by invasive device placement (10 [22.7%]) or arterial embolization (9 [20.5%]). Thirty-eight (86.4%) patients were able to be adequately graded for hemostatic efficacy. Overall, 30 (78.9%) patients achieved excellent or good hemostasis within 24h after periprocedural administration of andexanet alfa (19 [82.6%] apixaban vs. 11 [78.6%] rivaroxaban; 12 [80.0%] intracranial events vs. 18 [78.3%] extracranial events). Discharge disposition was most often to a short- or long-term care facilities (27 [61.4%]). Thirty-day mortality and thromboischemic complications occurred in 15 (34.1%) and 12 (27.3%) patients, respectively. Prothrombin time and antifactor Xa assay results were significantly decreased after andexanet alfa administration (p < 0.05) while thromboelastogram assay values (reaction time, kinetic time, and activated clotting time) showed nonsignificant changes pre- versus postreversal. Andexanet alfa may be used for urgent or emergent reversal of apixaban and rivaroxaban peri-procedurally with promising hemostatic outcomes. Further prospective, comparative clinical research is warranted.

Real-World Reversal of Factor Xa Inhibition in the Setting of Major Life-Threatening Bleeding or Urgent Surgery

Background: Management of major life-threatening bleeding with factor Xa (FXa) inhibition poses complex challenges involving novel direct reversal agents competing with non-specific preexisting strategies. The recent availability of andexanet alfa (AA) led to a health-system guideline incorporating its use alongside the most commonly used historic agent, four-factor prothrombin complex concentrate (4F-PCC). Objectives: The objective was to characterize the use and efficacy of AA and 4F-PCC for reversal of FXa inhibition after implementation of the health-system guideline. Methods: This multi-hospital, retrospective cohort study included patients aged >18 years administered either AA or 4F-PCC between October 2018 to June 2020 with the indication for urgent reversal of FXa inhibitor-induced coagulopathy. The primary outcome assessed hemostatic efficacy between treatment groups. Secondary outcomes evaluated adjunct blood product administration, incidence of repeat pharmacologic reversal, incidence of thromboembolism, intensive care unit and hospital length of stays, and in-hospital mortality. Results: Eighty-five patients were included; 33 patients received AA and 52 patients received 4F-PCC. Effective hemostasis was achieved at similar rates in both treatment groups (84.8% vs 76.9%; P = .373). Thrombotic events occurring during the observed hospitalization were more frequent among the AA treated group (18% vs 3.8%, P = .027). No differences were observed for other secondary outcomes. Conclusion: Guideline use resulted in similar rates of effective hemostasis with a higher incidence of VTE in patients receiving AA. Further exploration with a larger, prospective study to evaluate these findings is warranted.

Emergent anticoagulation reversal and BP control are key for ICH

Emergent anticoagulation reversal and BP control are key for ICH

Andexanet-Alfa-Associated Heparin Resistance in the Context of Hemorrhagic Stroke

BackgroundWith a growing number of patients on new oral anticoagulants, interest in reversal agents is rising. Andexanet alfa is used for reversal of factor Xa inhibitors in intracranial hemorrhage.MethodsWe provide a brief review on andexanet-alfa-associated heparin resistance and discuss potentially critical situations from different clinical perspectives.ResultsCase reports point out that andexanet alfa can cause unresponsiveness to heparin, leading to catastrophic events. As a result, regulatory bodies have issued warning notices to avoid heparinization parallel to the use of andexanet alfa.ConclusionsAlthough well known to hematologists, the phenomenon is underrecognized among stroke clinicians. However, patients with intracranial hemorrhage frequently undergo endovascular or surgical interventions that require periprocedural administration of heparin.

Management of perioperative bleeding risk in patients on antithrombotic medications undergoing cardiac surgery-a systematic review.

BackgroundAntithrombotic drugs increase the risk of bleeding, especially in patients who need urgent surgery without an adequate wash-out period. This review aims to evaluate perioperative bleeding complications in patients on dual antiplatelet therapy (DAPT) or direct-acting oral anticoagulants (DOACs) undergoing high-bleeding risk cardiovascular surgery and to present currently available potential solutions to mitigate antithrombotic therapy-related bleeding complications.MethodsAs a first step, we searched for relevant articles, over the last 10 years, in Medline (PubMed) and abstracted clinical information based on pre-defined criteria for bleeding complications. In the next step, an additional search evaluating potential solutions to mitigate bleeding complications was performed. The literature screening and selection process followed the principles derived from the PRISMA statement.ResultsFrom all reviewed studies, a total of 19 articles could be included evaluating the risk for bleeding in cardiac surgery related to DAPT or DOACs and 10 papers evaluating antithrombotic drug reversal or removal in the setting of cardiovascular surgery. Reported bleeding rates ranged between 18% and 41%. The variability of the reported data is remarkable. Idarucizumab is reported to provide optimal perioperative hemostasis in up to 93% of patients. It has been observed that andexanet alfa causes unresponsiveness to the anticoagulant effects of heparin. Antithrombotic removal by intraoperative hemoadsorption is found to be associated with a significant decrease in re-thoracotomy rate, overall procedure duration, administered transfusion volumes, chest-tube drainage, and length of hospitalization.DiscussionBleeding complications in patients treated with DAPT or DOACs in cardiac surgery are high. New costly reversal agents are available but have not been sufficiently tested in the cardio-surgical setting so far. Interestingly, bleeding-related complications seem to be effectively reduced by applying innovative intraoperative hemoadsorption techniques. Expected results from the ongoing trials should provide better insights concerning the efficacy and safety of several potential solutions. Currently, the variability of reports and the deficit of high-quality studies in this specific setting represent the major limitation for the unbiased conclusion of this review.

Dosing Medications for Coagulopathy Reversal in Patients with Extreme Obesity

BackgroundThe reversal of anticoagulant or antiplatelet medications is a priority in the management of patients with severe injury with the goal of minimizing further bleeding without thrombotic complications. There are few studies, however, evaluating the dosing of reversal agents in the setting of trauma specific to patients with extreme obesity. Nevertheless, clinicians must still make decisions, balancing concerns of ongoing bleeding with excessive thrombosis. ObjectivesWe describe the literature pertaining to dosing of medications used for the reversal of both drug-induced and trauma-related coagulopathy with the intent of providing a framework for clinicians to make dosing decisions in this challenging population. DiscussionObesity is known to impact both the volume of distribution and the clearance of medications, but these changes are not usually linear with size nor are they uniform across drugs. Current strategies for dosing reversal agents in obesity include a capped dose (e.g., prothrombin complex concentrates), fixed dosages (e.g., andexanet alfa, idarucizumab, and tranexamic acid), and weight-based dosing (e.g., desmopressin). Extreme obesity, however, was not highly prevalent in the studies that have validated these dosing strategies. In fact, many of the clinical studies fail to report the average weight of the patients included. ConclusionFuture studies should make efforts to increase reporting of patients with obesity included in clinical trials along with results stratified by weight class. In the meantime, doses listed in product labels should be used. Desmopressin should be dosed using either ideal body weight or a dose-capping strategy.

In vitro reversal of direct factor Xa inhibitors: Direct comparison of andexanet alfa and prothrombin complex concentrates Cofact and Beriplex/Kcentra

BackgroundBoth andexanet alfa and four‐factor prothrombin complex concentrate (4F‐PCC) are clinically applied reversal agents for direct factor Xa inhibitors (FXaIs) in emergency situations. Controversy exists whether 4F‐PCC is as effective as andexanet alfa in correcting FXaI anticoagulation. ObjectiveThis in vitro study was designed to directly compare andexanet alfa with two different 4F‐PCCs (Cofact and Beriplex/Kcentra) in their ability to correct FXaI anticoagulation. MethodNormal plasma was spiked with apixaban or rivaroxaban. Reversal of anticoagulation was assessed using a thrombin generation assay and a fibrin generation–clot lysis test. ResultsAndexanet alfa, applied at clinically recommended doses, was effective in restoring thrombin generation as evidenced by correction of thrombin generation lag time, peak thrombin, and endogenous thrombin potential (ETP). Clotting time and clot resistance to fibrinolytic breakdown was corrected over the full range of applied FXaI (0–800 ng/ml). 4F‐PCC in increasing doses (0.625, 1.25 and 2 IU/ml; approximately 25, 50, and 80 IU/kg) only partially restored thrombin generation lag time and clotting time. Partial correction to overnormalization of peak thrombin and ETP was observed, depending on FXaI concentration and PCC dose. Clot resistance to fibrinolytic breakdown was dose‐dependently improved to above normal. Beriplex/Kcentra was consistently less effective than Cofact. ConclusionBoth andexanet alfa and 4F‐PCC improved coagulation that is hampered by FXaIs. While andexanet alfa corrected all thrombin generation parameters, 4F‐PCC predominantly increased peak thrombin and ETP. Especially heparin‐free 4F‐PCC also improved clot stability against fibrinolytic breakdown. Beriplex/Kcentra contains heparin, and this may have caused reduced effectivity compared to Cofact.

Rapid Detection of Apixaban by a ROTEM-Based Approach and Reversibility with Andexanet Alfa or DOAC-Stop.

Background A rapid test to detect apixaban treatment would be useful in acute situations such as major bleeding, urgent surgery, or in acute thrombosis. Objective This article aims to study if the viscoelastic test rotational thromboelastometry (ROTEM) can rapidly detect apixaban in whole blood using modified triggers based on factor Xa (FXa) or Russell viper venom (RVV). Method ROTEM clotting time (CT) was measured in samples from 40 patients on apixaban treatment, and in vitro in samples spiked with apixaban (20–500 ng/mL). Commercially available trigger Ex-tem was compared with modified triggers based on FXa or RVV. Reversibility of apixaban in the samples was studied; CT was measured with and without addition of DOAC-Stop or andexanet alfa, respectively, and the difference in CT was calculated (CT diff ). Results Using FXa as trigger, we detected apixaban concentrations at 20 ng/mL and above with 100% sensitivity and 100% specificity in patient samples and in vitro. Corresponding data for Ex-tem were 92% sensitivity and 100% specificity in patients, and 94% sensitivity and 100% specificity in vitro, and for RVV 97% sensitivity and 94% specificity in patients, and 97% sensitivity and 100% specificity in vitro, respectively. CT diff data were similar. Patient sample data were obtained within 20 minutes from sampling. Conclusion Apixaban at low therapeutic concentrations was detected within 20 minutes, and with high sensitivity and specificity. A trigger based on FXa outperformed the commercial trigger Ex-tem and a trigger based on RVV. ROTEM with a FXa-based trigger is a promising method to detect apixaban bedside in acute settings.

Direct (New) Oral Anticoagulants (DOACs): Drawbacks, Bleeding and Reversal

Direct (new) Oral Anticoagulants (DOACs) have emerged as a contemporary and promising option in the treatment of thromboses and VTE, while protecting the coagulation cascade against untoward bleeding events. They are used in the management and prophylaxis of Venous Thromboembolism (VTE) and other thrombotic diseases. The most prominent complication of these agents is bleeding. These agents have similar or lower rates of major intracranial hemorrhages, while they had a higher risk of major gastrointestinal bleeding when compared to warfarin. This manuscript is aimed to revise and update the literature findings to outline the side effects of DOACs in various clinical scenarios. A narrative review of currently published studies was performed. Online database searches were performed for clinical trials published before July 2021, on the efficacy and adverse effects attributed to the anticoagulant treatment, especially DOACs. A literature search via electronic databases was carried out, beginning with the usage of the agents in the Western Languages papers. The search terms initially included direct (new) oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, idarucizumab, andexanet, prothrombin complex concentrates, and fresh frozen plasma. Papers were examined for methodological soundness before being included. Severe bleeding episodes require aggressive interventions for successful management. Therefore, bleeding should be evaluated in special regard to the location and rate of hemorrhage, and total volume of blood loss. Patient's age, weight and organ dysfunctions (e.g., kidney/liver failure or chronic respiratory diseases) directly affect the clinical course of overdose. Management recommendations for hemorrhage associated with DOAC use vary, depending on the class of the culprit agent (direct thrombin inhibitor vs. FXa inhibitor), the clinical status of the patient (mild/ moderate vs. severe/life-threatening), and capabilities of the institution. Specific reversal agents (i.e., idarucizumab and andexanet alfa) can be used if available, while prothrombin complex concentrates, fresh frozen plasma and/ or tranexamic acid can also be employed as nonspecific replacement agents in the management of DOAC-related bleeding diathesis.

EE391 Budget Impact of Andexanet ALFA for Gastrointestinal Bleeding Associated with Factor Xa Inhibitors from a US Hospital Perspective

Oral Factor Xa (FXa) inhibitors are used to treat and prevent thrombotic events but may exacerbate acute major bleeding. This analysis calculated the budget impact of using Andexanet alfa (andexanet), a novel specific reversal agent for FXa inhibitors, to treat FXa inhibitor-related major gastrointestinal bleeding from a US acute care hospital perspective.

Andexanet alfa versus four-factor prothrombin complex concentrate for the reversal of apixaban- or rivaroxaban-associated intracranial hemorrhage: a propensity score-overlap weighted analysis

BackgroundAndexanet alfa is approved (FDA “accelerated approval”; EMA “conditional approval”) as the first specific reversal agent for factor Xa (FXa) inhibitor-associated uncontrolled or life-threatening bleeding. Four-factor prothrombin complex concentrates (4F-PCC) are commonly used as an off-label, non-specific, factor replacement approach to manage FXa inhibitor-associated life-threatening bleeding. We evaluated the effectiveness and safety of andexanet alfa versus 4F-PCC for management of apixaban- or rivaroxaban-associated intracranial hemorrhage (ICH).MethodsThis two-cohort comparison study included andexanet alfa patients enrolled at US hospitals from 4/2015 to 3/2020 in the prospective, single-arm ANNEXA-4 study and a synthetic control arm of 4F-PCC patients admitted within a US healthcare system from 12/2016 to 8/2020. Adults with radiographically confirmed ICH who took their last dose of apixaban or rivaroxaban < 24 h prior to the bleed were included. Patients with a Glasgow Coma Scale (GCS) score < 7, hematoma volume > 60 mL, or planned surgery within 12 h were excluded. Outcomes were hemostatic effectiveness from index to repeat scan, mortality within 30 days, and thrombotic events within five days. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using propensity score-overlap weighted logistic regression.ResultsThe study included 107 andexanet alfa (96.6% low dose) and 95 4F-PCC patients (79.3% receiving a 25 unit/kg dose). After propensity score-overlap weighting, mean age was 79 years, GCS was 14, time from initial scan to reversal initiation was 2.3 h, and time from reversal to repeat scan was 12.2 h in both arms. Atrial fibrillation was present in 86% of patients. Most ICHs were single compartment (78%), trauma-related (61%), and involved the intracerebral and/or intraventricular space(s) (53%). ICH size was ≥ 10 mL in volume (intracerebral and/or ventricular) or ≥ 10 mm in thickness (subdural or subarachnoid) in 22% of patients and infratentorial in 15%. Andexanet alfa was associated with greater odds of achieving hemostatic effectiveness (85.8% vs. 68.1%; OR 2.73; 95% CI 1.16–6.42) and decreased odds of mortality (7.9% vs. 19.6%; OR 0.36; 95% CI 0.13–0.98) versus 4F-PCC. Two thrombotic events occurred with andexanet alfa and none with 4F-PCC.ConclusionsIn this indirect comparison of patients with an apixaban- or rivaroxaban-associated ICH, andexanet alfa was associated with better hemostatic effectiveness and improved survival compared to 4F-PCC.Trial registration NCT02329327; registration date: December 31, 2014.

Andexanet Alfa for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage: Observational Cohort Study.

Background: Intracranial hemorrhage (ICH) is associated with high mortality and morbidity, especially in patients under anticoagulative treatment. Andexanet alfa (AA) is a modified recombinant form of human factor Xa (FXa) developed for reversal of FXa-inhibitors, e.g., in the event of ICH, but experience is still limited. Methods: This monocentric retrospective observational cohort study included 46 patients with acute FXa-inhibitor-associated non-traumatic ICH (FXa-I-ICH) of whom 23 were treated with AA within 12 h after symptom onset, compared to 23 patients with usual care (UC). Volumetrically analyzed hematoma expansion (HE) in brain imaging, clinical outcome and incidence of adverse events were analyzed. Results: All patients (mean age 79.8 ± 7.2 years) were effectively anticoagulated. The cohort included severely ill patients with large hematoma volumes (median 20.4, IQR 7.8–39.0 mL). Efficacy, as assessed by HE in imaging, was very good in the AA-group. There was no (0.0%) relevant HE (>33%) in contrast to UC-group (26.1%). Nevertheless, we observed a high incidence of thromboembolic events (30.4% vs. 4.4%) and non-favorable outcomes (death/palliative condition) in 43.5% vs. 26.1%. Conclusions: There was no HE in the volumetric neuroimaging assessment in the AA-group, but clinical outcomes remained often worse. Large randomized trials for the use of AA in patients with acute FXa-inhibitor-associated ICH are needed to investigate the clinical outcome in consideration of the rates of thromboembolism.

Anticoagulation and bleeding in the cancer patient.

Cancer patients have an increased risk of bleeding compared to non-cancer patients with anticoagulant therapy. A bleeding risk assessment before initiation of anticoagulation is recommended. Currently low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) are the mainstays of treatment for cancer-associated venous thromboembolism (VTE). Since DOACs are administered orally, they offer some convenience and ease of administration; however, LMWH may be preferred in certain cancers. Given the prevalence of anticoagulant therapies in cancer patients, clinical providers must be able to recognize potentially critical bleeding sites and modalities to reverse major hemorrhage. Reversal agents or antidotes to bleeding may be required when bleeding is persistent or life-threatening. These include vitamin K, fresh frozen plasma (FFP), protamine, prothrombin complex concentrate (PCC) or andexanet alfa, and idarucizumab. Inferior vena cava (IVC) filter insertion can be also considered in those with major bleeding. Evidence for timing and need for re-initiation of anticoagulant therapy after a major bleeding remains sparse, but a multi-disciplinary approach and shared decision-making can be implemented in the interim.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

Andexanet alfa after 4-factor PCC administration for intracranial hemorrhage: a case series.

The ongoing controversy regarding optimal reversal agent for factor Xa-inhibitors is mainly due to lack of comparative data of andexanet alfa (AA) to 4-factor prothrombin complex concentrate (4F-PCC), institutional formulary restrictions, and navigation of clinical scenarios involving patients clinically worsen despite initial reversal efforts. The combination use of 4F-PCC and AA has not been evaluated in clinical trials and the outcomes of such patients with FXA-inhibitor associated intracranial hemorrhage (ICH) are unknown. A total of five patients, including four outside hospital transfers, received 4F-PCC prior to AA for FXa-inhibitor associated ICH (n = 3 apixaban, n = 2 rivaroxaban; n = 4 ICH, n = 1 TBI). The doses of 4F-PCC ranged from 25 to 60 units/kg and were administered within a range of 1.5-4.2h prior to AA. One patient required surgical intervention with craniotomy and three patients underwent external ventricular drain placement. Two of the five patients developed an ischemic or thromboembolic complication within one week from 4F-PCC and AA administration. This case series discusses multiple unique patient cases in which 4F-PCC and AA were both administered for FXa-inhibitor associated ICH. The results highlight thepotentially increased thrombotic risk associated with combination use. Ongoing post-marketing data collection of real patient case scenarios are essential to the establishment of consensus guidelines on how to prioritize initial reversal efforts and manage these patients during the course of their bleed.

PO-683-06 MULTICENTER EXPERIENCE WITH ANDEXANET ALFA FOR REFRACTORY PERICARDIAL BLEEDING DURING CATHETER ABLATION OF ATRIAL FIBRILLATION IN PATIENTS TAKING FACTOR XA INHIBITORS

Pericardial bleeding is a rare but life-threatening complication of atrial fibrillation (AF) ablation. When significant pericardial bleeding occurs, protamine should be given to reverse heparin and pericardiocentesis performed. Patients taking uninterrupted oral anticoagulation (AC) are at increased risk for refractory pericardial bleeding. In such cases, andexanet alfa, a recombinant, inactive form of factor Xa, can be given to reverse oral AC. Clinical experience with andexanet in this setting has not yet been reported.

Review of Target-Specific Anticoagulation Reversal Agents.

Bleeding related to direct oral anticoagulants accounts for nearly half of emergency department visits annually and until recently there were no reversal antidotes available. As there continues to be a shift in prescribing practices away from warfarin, it is essential to have these reversal agents readily available for the treatment of life-threatening bleeds associated with these anticoagulants. In addition, for agents that continue to lack a targeted reversal agent (eg, low-molecular-weight heparin, antiplatelets, and new antithrombotics), it is imperative that research continues to evaluate improved reversal strategies. This review focuses on target-specific anticoagulation reversal agents currently available in the United States (protamine, idarucizumab, and andexanet alfa) and summarizes agents that are in the pipeline for these anticoagulants and antiplatelets.

Cost-effectiveness of andexanet alfa versus four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-related intracranial hemorrhage in the US

Aim To conduct a cost-effectiveness analysis (CEA) on the use of andexanet alfa for the treatment of factor Xa inhibitor-related intracranial hemorrhage (ICH) from the US third-party payer and societal perspectives. Methods CEA compared andexanet alfa to prothrombin complex concentrate for the treatment of patients receiving factor Xa inhibitors admitted to hospital inpatient care with an ICH. The model comprised two linked phases. Phase 1 utilized a decision tree to model the acute treatment phase (admission of a patient with ICH into intensive care for the first 30 days). Phase 2 modeled long-term costs and outcomes using three linked Markov models comprising the six health states defined by the modified Rankin score. Results The analysis showed that the strategy of using andexanet alfa for the treatment of factor Xa inhibitor-related ICH is cost-effective, with incremental cost-effectiveness per quality-adjusted life-year gained of $35,872 from a third-party payer perspective and $40,997 from a societal perspective over 20 years. Limitations (1) Absence of head-to-head trials comparing therapies included in the economic model, (2) lack of comparative long-term data on treatment efficacy, and (3) bias resulting from the study designs of published literature. Conclusion Given these results, the use of andexanet alfa for the reversal of anticoagulation in patients with factor Xa inhibitor-related ICH may improve quality of life and is likely to be cost-effective in a US context.