Evidence map›Paper›PMID 27573206›Full record

Trial reportThe New England journal of medicine2016

Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.

Stuart J Connolly, Truman J Milling, John W Eikelboom, C Michael Gibson, John T Curnutte, Alex Gold, Michele D Bronson, Genmin Lu, Pamela B Conley, Peter Verhamme and 16 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 264 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
264citing papers in PubMed, 9 pooled it
111.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02329327 phase3completednot on this map

Prospective, Open-Label Study of Andexanet Alfa in Patients Receiving a Factor Xa Inhibitor Who Have Acute Major Bleeding (ANNEXA-4)

TypeinterventionalSponsorAlexion Pharmaceuticals, Inc.Ran2015 to 2020Enrolled479ConditionsBleedingArmsAndexanet
NCT03021928 phase3unknown statusnot on this mapstarted 2017, after this paper: background citation

Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation

TypeinterventionalSponsorUniversity of Texas at AustinRan2017 to 2023Enrolled200ConditionsStrokeArmsTime-To-Treatment Randomization
3 · Its place in the literature

Who cites it

264 citing papers in PubMed, 9 syntheses or guidelines pooled it, 781 citations in OpenAlex.

  1. Pooled it
  2. Optimal management of cardiac surgery patients using direct oral anticoagulants: recommendations for clinical practice.European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery · 2023
    Pooled it
  3. Guideline
  4. Guideline
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  6. The Reversal of Bleeding Caused by New Oral Anticoagulants (NOACs): A Systematic Review and Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018
    Pooled it
  7. Guideline
  8. Pooled it
  9. Guideline
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Article
  15. Article
  16. Review
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204 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 11 institutions in 8 countries.

Stuart J ConnollyFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Truman J MillingFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
John W EikelboomFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
C Michael GibsonFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
John T CurnutteFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Alex GoldFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Michele D BronsonFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Genmin LuFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Pamela B ConleyFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Peter VerhammeFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Jeannot SchmidtFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Saskia MiddeldorpFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Alexander T CohenFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Jan Beyer-WestendorfFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Pierre AlbaladejoFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Jose Lopez-SendonFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Shelly GoodmanFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Janet LeedsFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Brian L WiensFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Deborah M SiegalFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Elena ZotovaFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Brandi MeeksFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Juliet NakamyaFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
W Ting LimFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
Mark CrowtherFrom the Population Health Research Institute, McMaster University, Hamilton ON, Canada (S.J.C., J.W.E., D.M.S., E.Z., B.M., J.N., W.T.L., M.C.); Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.); Harvard Medical School, Boston (C.M.G.); Portola Pharmaceuticals, San Francisco (J.T.C., A.G., M.D.B., G.L., P.B.C., S.G., J.L., B.L.W.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); and Hospital Universitario La Paz, Madrid (J.L.-S.).
ANNEXA-4 Investigators
Portola Pharmaceuticals (United States) · USPopulation Health Research Institute · CAMcMaster University · CAAcademic Medical Center · NLCentre Hospitalier Universitaire de Clermont-Ferrand · FRHarvard University · USHospital Universitario La Paz · ESKU Leuven · BESt Thomas' Hospital · GBUniversité Grenoble Alpes · FRUniversity Hospital Carl Gustav Carus · DE

Funding

A Patient Centered Approach to Restarting Oral Anticoagulant Therapy After Major HemorrhageK23HL127227 · NHLBI · SETON HEALTHCARE · PI MILLING, TRUMAN · 2016 to 2021
$764k
NHLBI NIH HHS K23 HL127227
6 · The paper itself

Abstract

backgroundAndexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers.

methodsIn this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication.

resultsThe mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up.

conclusionsOn the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327 .).

Indexed as

Acute DiseaseAgedAged, 80 and overCardiovascular DiseasesEnoxaparinFactor XaFactor Xa InhibitorsFemaleGastrointestinal HemorrhageHemorrhageHumansInfusions, IntravenousIntracranial HemorrhagesMaleProspective StudiesPyrazolesapixabanEnoxaparinFactor XaFactor Xa InhibitorsPRT064445PyrazolesPyridonesRecombinant ProteinsRivaroxaban

Identifiers

PMID27573206
PMCPMC5568772
OpenAlexW2514338974

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.