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579 The Efficacy and Safety of Andexanet Alfa in Patients With Acute Gastrointestinal Bleeding While Taking Factor Xa Inhibitors: An ANNEXA-4 Sub-Analysis

2019· article· en· W2980003404 on OpenAlexaff
Deborah Siegal, Jan Beyer‐Westendorf, Patrick Yue, Sônia Francisca de Souza, Juliet Nakamya, Stuart J. Connolly, Mark Crowther

Bibliographic record

VenueThe American Journal of Gastroenterology · 2019
Typearticle
Languageen
FieldMedicine
TopicAtrial Fibrillation Management and Outcomes
Canadian institutionsMcMaster University
Fundersnot available
KeywordsMedicineRivaroxabanEdoxabanHemostasisInternal medicineDosingGastrointestinal bleedingMajor bleedingAnesthesiaGastroenterologyApixabanSurgeryWarfarin

Abstract

fetched live from OpenAlex

INTRODUCTION: Andexanet alfa is a recombinant modified human Factor Xa (FXa) decoy protein developed to reverse the anticoagulant effect of FXa inhibitors. METHODS: ANNEXA-4 was a prospective single-arm study of andexanet alfa in patients with acute major bleeding while taking a FXa inhibitor. Patients with major gastrointestinal (GI) bleeding were eligible if they had (1) signs/symptoms of hemodynamic compromise or (2) bleeding associated with a hemoglobin (Hb) drop ≥2 g/dL or baseline Hb ≤8 g/dL. Upon enrollment, patients were treated with one of two andexanet dosing regimens based on the type, timing, and dose of the most recent inhibitor intake. Efficacy was evaluated in all patients who met the bleeding criteria above and had a baseline anti-FXa activity ≥75 ng/mL (≥0.25 IU/mL for enoxaparin). Co-primary endpoints were the change in anti-FXa activity and the achievement of hemostasis, as adjudicated by an independent committee, at 12 hours after andexanet treatment. Hemostasis was defined as: excellent if the red blood cell transfusion-corrected Hb at 12 hours was ≤10% lower than baseline, good if Hb was 10-20% lower, and poor/none if Hb was >20% lower. RESULTS: Of 352 patients enrolled in the study, 90 had GI bleeding, of whom 62 were included in the efficacy analysis. Median age was 76 years (range 24-95); 51 (57%) were male. Patients were receiving rivaroxaban (n = 44), apixaban (n = 5), and edoxaban (n = 3) at study entry. Bleeding location was identified in 48 patients (upper n=27, lower n = 21) and unknown in 42 patients. 66 (73%) patients had some evidence of hemodynamic compromise, including 38 (42%) patients with hypotension. Mean Hb at the time of dosing was 4.9 ± 1.4 g/dL. In patients taking rivaroxaban, the baseline anti-FXa activity was 267 ± 168.5 ng/mL and the percent reduction with andexanet was 94% (95%CI 89-96). In apixaban patients, the baseline anti-FXa activity was 244 ± 215.0 ng/mL and the percent reduction with andexanet was 92% (95%CI 88-95). Excellent/good hemostasis was achieved in 85% of evaluable patients. 58 (94%) of 62 patients received red blood cell transfusions, 3 (5%) received platelet transfusion, and 2 (3%) received a coagulation factor product. 30-day rates of thrombosis and death were 6% and 13%, respectively. CONCLUSION: In patients with major GI bleeding treated with andexanet, a high rate of effective hemostasis was achieved. The thrombosis and mortality rates are consistent with prior studies in this patient population.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.005
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.017
GPT teacher head0.272
Teacher spread0.255 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations4
Published2019
Admission routes1
Has abstractyes

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