Abstract TP352: Safety and Efficacy of Andexanet Alfa in Patients With Life Threatening Intracerebral Hemorrhage: A Single Center Experience

Background: Intracerebral hemorrhage (ICH) is a devastating condition with high 30- day mortality. Up to a third of patients experience hematoma expansion within the first 24 hours; anticoagulation with factor Xa inhibitors may increase the risk of expansion and poor outcomes. Objective: We assessed our experience using Andexanet alfa (Aα) by evaluating stabilization of the hematoma and ischemic complications. Methods: We conducted a single center prospective observational study on all patients receiving Aα for reversal of anticoagulation in the setting of an ICH and use of Factor Xa inhibitors. The degree of hematoma expansion within 12 hours of drug administration on non-contrast head CT was categorized as 'excellent' (<20% increase in hematoma size), ‘good' ( > 20-<35%), and 'poor' ( > 35%). Secondary outcomes included dosage, median length of stay, mortality, modified Rankin score (mRS), discharge disposition, and ischemic complications. Results: Fifteen patients received Aα (5=lobar, 5=deep, 5= multicompartment). One patient with a presumed deep hemorrhage was excluded because subsequent imaging showed chronic mineralization. The predominant etiologies were hypertension (40%), amyloid angiopathy (26.6%) and trauma (13.3%). The median age was 86 years (IQR 19) and median ICH score on arrival was 2 (IQR 2), and median hematoma size was 14.3 mL (IQR 34.5). Most patients (71.4%) received the low dose formulation. Based on hematoma expansion, 64.3%, 14.3% and 21.4% of patients achieved excellent, good and poor hemostasis, respectively. Reduction in hematoma size was seen in 20% (n=3) while 13.3% (n=2) patients had no expansion. Median ICU and hospital length of stays were 2.0 days (IQR 2.2) and 6.6 days (IQR 9.78) respectively. Mortality was 28.6% and median mRS upon discharge was 4 (IQR 2), with most patients discharged to rehabilitation facilities (60%). There were no ischemic complications. Conclusion: Our experience is consistent with the results of the ANNEXA 4 study with 78.6% of patients showing excellent or good hemostasis. These results led to improved clinical outcomes, with 60% of patients being discharged to rehabilitation. These data support the efficacy of this treatment paradigm in a real-world setting.

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Hematoma Expansion and Clinical Outcomes in Patients With Factor-Xa Inhibitor–Related Atraumatic Intracerebral Hemorrhage Treated Within the ANNEXA-4 Trial Versus Real-World Usual Care

Stroke ◽

10.1161/strokeaha.121.034572 ◽

2021 ◽

Author(s):

Hagen B. Huttner ◽

Stefan T. Gerner ◽

Joji B. Kuramatsu ◽

Stuart J. Connolly ◽

Jan Beyer-Westendorf ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Hospital Mortality ◽

Usual Care ◽

Clinical Outcomes ◽

Factor Xa ◽

Hematoma Expansion ◽

Factor Xa Inhibitor ◽

Hematoma Volume ◽

Prothrombin Complex Concentrates ◽

Andexanet Alfa

Background and Purpose: It is unestablished whether andexanet alfa, compared with guideline-based usual care including prothrombin complex concentrates, is associated with reduced hematoma expansion (HE) and mortality in patients with factor-Xa inhibitor–related intracerebral hemorrhage (ICH). We compared the occurrence of HE and clinical outcomes in patients treated either with andexanet alfa or with usual care during the acute phase of factor-Xa inhibitor–related ICH. Methods: Data were extracted from the multicenter, prospective, single-arm ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors) and a multicenter observational cohort study, RETRACE-II (German-Wide Multicenter Analysis of Oral Anticoagulant-Associated Intracerebral Hemorrhage - Part Two). HE was based on computed tomography scans performed within 36 hours from baseline imaging. Inverse probability of treatment weighting was performed to adjust for baseline comorbidities and ICH severity. Patients presenting with atraumatic ICH while receiving apixaban or rivaroxaban within 18 hours of admission were included. Patients with secondary ICH or not fulfilling the inclusion criteria for the ANNEXA-4 trial were excluded. We compared ANNEXA-4 patients, who received andexanet alfa for hemostatic treatment, with RETRACE-II patients who were treated with usual care, primarily administration of prothrombin complex concentrates. Primary outcome was rate of HE defined as relative increase of ≥35%. Secondary outcomes comprised mean absolute change in hematoma volume, as well as in-hospital mortality and functional outcome. Results: Overall, 182 patients with factor-Xa inhibitor–related ICH (85 receiving andexanet alfa versus 97 receiving usual care) were selected for analysis. There were no relevant differences regarding demographic or clinical characteristics between both groups. HE occurred in 11 of 80 (14%) andexanet alfa patients compared with 21 of 67 (36%) usual care patients (adjusted relative risk, 0.40 [95% CI, 0.20–0.78]; P =0.005), with a reduction in mean overall hematoma volume change of 7 mL. There were no statistically significant differences among in-hospital mortality or functional outcomes. Sensitivity analysis including only usual care patients receiving prothrombin complex concentrates demonstrated consistent results. Conclusions: As compared with usual care, andexanet alfa was associated with a lower rate of HE in atraumatic factor-Xa inhibitor–related ICH, however, without translating into significantly improved clinical outcomes. A comparative trial is needed to confirm the benefit on limiting HE and to explore clinical outcomes across patient subgroups and by time to treatment.

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A New Option for Reversing the Anticoagulant Effect of Factor Xa Inhibitors: Andexanet Alfa (ANDEXXA)

The American Journal of Medicine ◽

10.1016/j.amjmed.2018.06.028 ◽

2019 ◽

Vol 132 (1) ◽

pp. 38-41 ◽

Cited By ~ 16

Author(s):

Kelly C. Rogers ◽

Shannon W. Finks

Keyword(s):

Factor Xa ◽

Anticoagulant Effect ◽

Factor Xa Inhibitors ◽

Andexanet Alfa

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Andexanet alfa for the reversal of factor Xa inhibitors

Expert Opinion on Biological Therapy ◽

10.1080/14712598.2019.1599355 ◽

2019 ◽

Vol 19 (5) ◽

pp. 387-397 ◽

Cited By ~ 3

Author(s):

J Favresse ◽

M Hardy ◽

MA van Dievoet ◽

AL Sennesael ◽

J Douxfils ◽

...

Keyword(s):

Factor Xa ◽

Factor Xa Inhibitors ◽

Andexanet Alfa

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Andexanet alfa for reversal of factor Xa inhibitors induced-anticoagulation in nonclinical and clinical studies

Frontiers in Bioengineering and Biotechnology ◽

10.3389/conf.fbioe.2016.01.03004 ◽

2016 ◽

Vol 4 ◽

Author(s):

Lu Genmin ◽

Pine Polly ◽

Leeds Janet ◽

Castillo Janice ◽

Curnutte John ◽

...

Keyword(s):

Clinical Studies ◽

Factor Xa ◽

Factor Xa Inhibitors ◽

Andexanet Alfa

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Andexanet Alfa for Bleeding with Factor Xa Inhibitors

New England Journal of Medicine ◽

10.1056/nejmc1906058 ◽

2019 ◽

Vol 381 (2) ◽

pp. 191-193 ◽

Cited By ~ 1

Keyword(s):

Factor Xa ◽

Factor Xa Inhibitors ◽

Andexanet Alfa

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Abstract W P257: Predictors of the CT Angiography Spot Sign in Deep and Lobar Intracerebral Hemorrhage

Stroke ◽

10.1161/str.45.suppl_1.wp257 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Farid Radmanesh ◽

Guido J Falcone ◽

Christopher D Anderson ◽

Thomas W Battey ◽

Alison M Ayres ◽

...

Keyword(s):

Logistic Regression ◽

Intracerebral Hemorrhage ◽

Ct Angiography ◽

Cerebral Amyloid Angiopathy ◽

Symptom Onset ◽

Hematoma Expansion ◽

Amyloid Angiopathy ◽

Spot Sign ◽

Increased Risk ◽

Cerebral Amyloid

Objectives: Intracerebral hemorrhage (ICH) patients with CT angiography (CTA) spot sign are at increased risk of hematoma expansion and poor outcome. Since ICH is often the acute manifestation of a chronic cerebral vasculopathy, we investigated whether different clinical or imaging characteristics predict spot sign presence in patients with different underlying vasculopathies. Using ICH location as a surrogate for hypertension-related ICH and cerebral amyloid angiopathy-related ICH, we identified risk factors associated with spot sign. METHODS: We retrospectively analyzed a prospective cohort of consecutive spontaneous ICH patients with available CTA. Spot sign presence was ascertained by two independent readers blinded to clinical data. We assessed potential predictors of spot sign be performing uni- and multivariable logistic regression, analyzing deep and lobar ICH separately. RESULTS: 649 patients were eligible, 291 (45%) deep and 358 (55%) lobar ICH. Median time from symptom onset to CTA was 4.5 (IQR 5.2) and 5.7 (IQR 7.4) hours in patients with deep and lobar ICH, respectively. At least one spot sign was present in 76 (26%) deep and 103 (29%) lobar ICH patients. In mutivariable logistic regression, independent predictors of spot sign in deep ICH were warfarin (OR 2.82 [95%CI 1.06-7.57]; p=0.03), time from symptom onset to CTA (OR 0.9 [95%CI 0.81-0.97]; p=0.02), and baseline ICH volume (OR 1.27 [95%CI 1.14-1.43]; p=2.5E-5; per 10 mL increase). Predictors of spot sign in lobar ICH were preexisting dementia (OR 2.7 [95%CI 1.15-6.43]; p=0.02), warfarin (OR 4.01 [95%CI 1.78-9.29]; p=0.009), and baseline ICH volume (OR 1.27 [95%CI 1.17-1.39]; p=5.4E-8; per 10 mL increase). As expected, spot sign presence was a strong predictor of hematoma expansion in both deep (OR 3.52 [95%CI 1.72-7.2]; p=0.0005) and lobar ICH (OR 6.53 [95%CI 3.23-13.44]; p=2.2E-7). CONCLUSIONS: The most potent associations with spot sign are shared by deep and lobar ICH, suggesting that ICH caused by different vasculopathic processes share biological features. The relationship between preexisting dementia and spot sign in lobar ICH, but not deep ICH, suggests that ICH occurring in the context of more advanced cerebral amyloid angiopathy may be more likely to have prolonged bleeding.

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Safety and Costs of Stroke Unit Admission for Select Acute Intracerebral Hemorrhage Patients

The Neurohospitalist ◽

10.1177/1941874417712158 ◽

2017 ◽

Vol 8 (1) ◽

pp. 12-17 ◽

Cited By ~ 2

Author(s):

Corey R. Fehnel ◽

Kimberly M. Glerum ◽

Linda C. Wendell ◽

N. Stevenson Potter ◽

Brian Silver ◽

...

Keyword(s):

Length Of Stay ◽

Intracerebral Hemorrhage ◽

Functional Outcome ◽

Stroke Unit ◽

Skilled Nursing Facility ◽

Patient Characteristics ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Discharge Disposition ◽

Group 5

Background and Purpose: There are limited data to guide intensive care unit (ICU) versus dedicated stroke unit (SU) admission for intracerebral hemorrhage (ICH) patients. We hypothesized select patients can be safely cared for in SU versus ICU at lower costs. Methods: We conducted a retrospective cohort study of consecutive patients with predefined minor ICH (≤20 cm3, supratentorial, no coagulopathy) receiving care in either an ICU or an SU. Multiple linear regression and inverse probability weighting were used to adjust for differences in patient characteristics and nonrandom ICU versus SU assignment. The primary outcome was poor functional status at discharge (modified Rankin score [mRS] ≥3). Secondary outcomes included complications, discharge disposition, hospital length of stay, and direct inpatient costs. Results: The study population included 104 patients (41 admitted to the ICU and 63 admitted to the SU). After controlling for differences in baseline characteristics, there were no differences in poor functional outcome at discharge (93% vs 85%, P = .26) or in mean mRS (2.9 vs 3.0, P = .73). Similarly, there were no differences in the rates of complications (6% vs 10%, P = .44), discharged dead or to a skilled nursing facility (8% vs 13%, P = .59), or direct patient costs (US$7100 vs US$6200, P = .33). Median length of stay was significantly longer in the ICU group (5 vs 4 days, P = .01). Conclusions: This study revealed a shorter length of stay but no large differences in functional outcome, safety, or cost among patients with minor ICH admitted to a dedicated SU compared to an ICU.

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