Andexanet alfa—The first 150 days

Culbreth, Sarah; Rimsans, Jessica; Sylvester, Katelyn W.; Pallin, Daniel J.; Connors, Jean M.

doi:10.1002/ajh.25326

Cited by 27 publications

(32 citation statements)

References 6 publications

(6 reference statements)

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“…We report a 19% incidence of ischemic complications, which falls within the 0% to 31% range reported in previous andexanet alfa reversal studies 17,18,20‐22 . Importantly, andexanet alfa is not a procoagulant agent, but a decoy molecule that temporarily impairs anti‐FXa activity.…”

Section: Discussionsupporting

confidence: 79%

“…In our study we report a median 106 minutes between admission and antidote administration, and 64 minutes between antidote administration and surgical intervention on those patients who required it. Both the time to reversal and the time to surgery fall within the ranges of previous studies that reported it 17,18,22 . Considering the short half‐lives of FXa inhibitors, a delay in administering andexanet alfa will mean a slight reduction of anti‐FXa plasma levels, which also depends on the patient's ability to clear the drug.…”

Section: Discussionsupporting

confidence: 66%

“…We found andexanet alfa reversal for FXa inhibitor‐associated extracranial bleeding had a lower rate of hemostatic effectiveness compared with previous studies on DOAC‐associated bleeding. In prior studies evaluating reversal of FXa inhibitor‐associated bleeding with andexanet alfa, hemostatic effectiveness ranged from 57% to 91%, compared to 48% in our cohort 17,18,20‐22 . The relatively low rate of hemostatic effectiveness found in our study is potentially explained through differences in patient selection, as patients requiring surgical intervention were excluded in the ANNEXA‐4 trial 20 .…”

Section: Discussionmentioning

confidence: 60%

“…Patient selection for andexanet alfa reversal in intracranial versus extracranial bleeding is based on different factors, as patient presentation is highly variable. Reversal with andexanet alfa for intracranial hemorrhage at our institutions has been previously described 17,18 . In this study, we aimed to describe patient selection, clinical effectiveness, and safety of oral FXa inhibitor reversal with andexanet alfa in patients presenting with extracranial bleeding.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Evaluation of oral factor Xa inhibitor‐associated extracranial bleeding reversal with andexanet alfa

Nederpelt

Naar

Sylvester

et al. 2020

Journal of Thrombosis and Haemostasis

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Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of oral factor Xa inhibitor‐associated extracranial bleeding reversal with andexanet alfa

Nederpelt

Naar

Sylvester

et al. 2020

Journal of Thrombosis and Haemostasis

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“…It would be helpful to see the comparable data from ANNEXA-4 to confirm or repute our hypothesis that ANNEXA-4 patients were less clinically ill than realworld patients. Additionally, a small case series from a tertiary referral center reported 40% inpatient mortality with Andexxa even though some of the patients in this case series would have been excluded from the ANNEXA-4 trial [18]. The lack of comparison group in ANNEXA-4 and the unique set of exclusions not seen in any other trials preclude any certainty whatsoever in comparing Andexxa mortality rates to other studies or databases.…”

Section: Evaluate Annexa-4 Unique Exclusion Criteria and Its Impact Omentioning

confidence: 95%

Key Points to Consider When Evaluating Andexxa for Formulary Addition

2019

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, Andexxa (coagulation factor Xa [recombinant], inactivated-zhzo or formerly andexanet alfa) received accelerated approval from the Food and Drug Administration (FDA) as a specific reversal for rivaroxaban-and apixaban-treated patients with life-threatening or uncontrolled bleeding despite not establishing improvement in hemostasis [1]. The recent publication of ANEXXA-4 and the wider availability for Andexxa in 2019 has led many hospital Pharmacy and Therapeutics (P&T) committees to discuss whether Andexxa should be added to formulary [2]. Currently, there are no studies comparing the safety and efficacy of Andexxa to the current standard of care. The ANNEXA-4 study and clinical trials with prothrombin complex concentrate (PCC) also have their limitations. Furthermore, the off-label use and FDA concerns, conflicting society recommendations, and financial impact add another challenging layer to this evaluation. In this article, we discuss key aspects to consider when evaluating Andexxa for formulary addition.

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Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

et al. 2022

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ImportanceDirect oral anticoagulant (DOAC)–associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.ObjectiveTo evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.Data SourcesPubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.Study SelectionThe eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.Data Extraction and SynthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.Main Outcomes and MeasuresThe primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.ResultsA total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.Conclusions and RelevanceIn the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.

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Andexanet alfa—The first 150 days

Cited by 27 publications

References 6 publications

Evaluation of oral factor Xa inhibitor‐associated extracranial bleeding reversal with andexanet alfa

Evaluation of oral factor Xa inhibitor‐associated extracranial bleeding reversal with andexanet alfa

Key Points to Consider When Evaluating Andexxa for Formulary Addition

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage

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