55 Andexanet Alfa is Associated with Reduced In-hospital Mortality Compared to 4-Factor Prothrombin Complex Concentrate among Patients with Intracranial or Gastrointestinal Bleeding

Study ObjectivesThere 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.MethodsThis multicenter retrospective cohort study used patient chart data collected from 182 US hospitals of varying type (academic, non-academic, designated trauma and/or stroke center) and size between May 17, 2018 and September 30, 2021. Included patients were aged ≥18 years, had an International Classification of Diseases-10th Revision (ICD-10) diagnosis code of D68.32 (bleeding due to extrinsic anticoagulants) as part of inpatient admission, a record of FXa inhibitor or enoxaparin use, were treated with AA or 4F-PCC during index hospitalization, and had a documented discharge disposition. Propensity scores were estimated using logistic regression, with multiple imputations for missing values, to create inverse probabilities of treatment weights to balance the two treatment groups. All available baseline variables including age, sex, comorbidities, systolic blood pressure, international normalized ratio, and albumin were included in the propensity score models. The primary outcome was in-hospital mortality. For each bleed type (ICH; GI), odds ratios (OR) across bleed cause (spontaneous; traumatic) were determined by estimating the weights within strata defined by bleed cause.ResultsThis study included data from 2,451 patients (AA, n=1,196; 4F-PCC, n=1,255) and 179 deaths. There were 754 patients with ICH (spontaneous, n=336; traumatic, n=418) and 1,697 patients with a GI bleed (spontaneous, n=1,400; traumatic, n=297). Among ICH patients, in-hospital mortality incidence ranged from 10%-17% for AA and 14%-24% for 4F-PCC, depending on the bleed cause. For GI bleed, in-hospital mortality incidence ranged from 2.0%-2.5% for AA and 3.3%-7.5% for 4F-PCC, depending on the bleed cause. In the overall weighted analysis, the odds for in-hospital mortality were lower for AA versus 4F-PCC (OR: 0.67 [95% CI: 0.48-0.94]) (Figure). The ORs were consistent across bleed type and cause, suggesting AA was associated with reduced in-hospital mortality compared to 4F-PCC (ORs ranging from 0.26 and 0.76).ConclusionIn this large retrospective study, treatment of oral FXa inhibitor- or enoxaparin-related ICH and GI bleeding hospitalizations with AA was associated with a 33% reduction in odds of in-hospital mortality compared to 4F-PCC. Effectiveness of AA versus 4F-PCC was consistent across ICH and GI bleeds.Yes, authors have interests to discloseDisclosureJanssen Pharmaceuticals (Speaker's bureau); AstraZeneca (Speaker's bureau); Siemens (Research funding); PCORI (Research funding); NIH (Research funding); Milestone Pharmaceuticals (Consultant)OtherJanssen Pharmaceuticals (Speaker's bureau); AstraZeneca (Speaker's bureau); Siemens (Research funding); PCORI (Research funding); NIH (Research funding); Milestone Pharmaceuticals (Consultant)DisclosurePfizer/Bristol Myers Squibb Alliance; Janssen PharmaceuticalsConsultant/AdvisorPfizer/Bristol Myers Squibb Alliance; Janssen PharmaceuticalsDisclosureOutcomes InsightsEmployeeOutcomes InsightsDisclosureAlexion, AstraZeneca Rare DiseaseEmployeeAlexion, AstraZeneca Rare DiseaseDisclosureJanssen Pharmaceuticals (Research funding); Bayer AG (Research funding); Alexion Pharmaceuticals (Research funding); Janssen Pharmaceuticals (Consulting honoraria); Bayer AG (Consulting honoraria); Alexion Pharmaceuticals (Consulting honoraria)OtherJanssen Pharmaceuticals (Research funding); Bayer AG (Research funding); Alexion Pharmaceuticals (Research funding); Janssen Pharmaceuticals (Consulting honoraria); Bayer AG (Consulting honoraria); Alexion Pharmaceuticals (Consulting honoraria) Study ObjectivesThere 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. 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. MethodsThis multicenter retrospective cohort study used patient chart data collected from 182 US hospitals of varying type (academic, non-academic, designated trauma and/or stroke center) and size between May 17, 2018 and September 30, 2021. Included patients were aged ≥18 years, had an International Classification of Diseases-10th Revision (ICD-10) diagnosis code of D68.32 (bleeding due to extrinsic anticoagulants) as part of inpatient admission, a record of FXa inhibitor or enoxaparin use, were treated with AA or 4F-PCC during index hospitalization, and had a documented discharge disposition. Propensity scores were estimated using logistic regression, with multiple imputations for missing values, to create inverse probabilities of treatment weights to balance the two treatment groups. All available baseline variables including age, sex, comorbidities, systolic blood pressure, international normalized ratio, and albumin were included in the propensity score models. The primary outcome was in-hospital mortality. For each bleed type (ICH; GI), odds ratios (OR) across bleed cause (spontaneous; traumatic) were determined by estimating the weights within strata defined by bleed cause. This multicenter retrospective cohort study used patient chart data collected from 182 US hospitals of varying type (academic, non-academic, designated trauma and/or stroke center) and size between May 17, 2018 and September 30, 2021. Included patients were aged ≥18 years, had an International Classification of Diseases-10th Revision (ICD-10) diagnosis code of D68.32 (bleeding due to extrinsic anticoagulants) as part of inpatient admission, a record of FXa inhibitor or enoxaparin use, were treated with AA or 4F-PCC during index hospitalization, and had a documented discharge disposition. Propensity scores were estimated using logistic regression, with multiple imputations for missing values, to create inverse probabilities of treatment weights to balance the two treatment groups. All available baseline variables including age, sex, comorbidities, systolic blood pressure, international normalized ratio, and albumin were included in the propensity score models. The primary outcome was in-hospital mortality. For each bleed type (ICH; GI), odds ratios (OR) across bleed cause (spontaneous; traumatic) were determined by estimating the weights within strata defined by bleed cause. ResultsThis study included data from 2,451 patients (AA, n=1,196; 4F-PCC, n=1,255) and 179 deaths. There were 754 patients with ICH (spontaneous, n=336; traumatic, n=418) and 1,697 patients with a GI bleed (spontaneous, n=1,400; traumatic, n=297). Among ICH patients, in-hospital mortality incidence ranged from 10%-17% for AA and 14%-24% for 4F-PCC, depending on the bleed cause. For GI bleed, in-hospital mortality incidence ranged from 2.0%-2.5% for AA and 3.3%-7.5% for 4F-PCC, depending on the bleed cause. In the overall weighted analysis, the odds for in-hospital mortality were lower for AA versus 4F-PCC (OR: 0.67 [95% CI: 0.48-0.94]) (Figure). The ORs were consistent across bleed type and cause, suggesting AA was associated with reduced in-hospital mortality compared to 4F-PCC (ORs ranging from 0.26 and 0.76). This study included data from 2,451 patients (AA, n=1,196; 4F-PCC, n=1,255) and 179 deaths. There were 754 patients with ICH (spontaneous, n=336; traumatic, n=418) and 1,697 patients with a GI bleed (spontaneous, n=1,400; traumatic, n=297). Among ICH patients, in-hospital mortality incidence ranged from 10%-17% for AA and 14%-24% for 4F-PCC, depending on the bleed cause. For GI bleed, in-hospital mortality incidence ranged from 2.0%-2.5% for AA and 3.3%-7.5% for 4F-PCC, depending on the bleed cause. In the overall weighted analysis, the odds for in-hospital mortality were lower for AA versus 4F-PCC (OR: 0.67 [95% CI: 0.48-0.94]) (Figure). The ORs were consistent across bleed type and cause, suggesting AA was associated with reduced in-hospital mortality compared to 4F-PCC (ORs ranging from 0.26 and 0.76). ConclusionIn this large retrospective study, treatment of oral FXa inhibitor- or enoxaparin-related ICH and GI bleeding hospitalizations with AA was associated with a 33% reduction in odds of in-hospital mortality compared to 4F-PCC. Effectiveness of AA versus 4F-PCC was consistent across ICH and GI bleeds.Yes, authors have interests to disclose In this large retrospective study, treatment of oral FXa inhibitor- or enoxaparin-related ICH and GI bleeding hospitalizations with AA was associated with a 33% reduction in odds of in-hospital mortality compared to 4F-PCC. Effectiveness of AA versus 4F-PCC was consistent across ICH and GI bleeds.