Evidence map›Paper›PMID 30730782›Full record

ArticleThe New England journal of medicine2019

Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors.

Stuart J Connolly, Mark Crowther, John W Eikelboom, C Michael Gibson, John T Curnutte, John H Lawrence, Patrick Yue, Michele D Bronson, Genmin Lu, Pamela B Conley and 20 more

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

Article in The New England journal of medicine, 2019. 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 330 papers, 18 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
330citing papers in PubMed, 18 pooled it
92.6field-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
NCT06393868 phase3recruitingnot on this mapstarted 2024, after this paper: background citation

Reducing Gastrointestinal Bleeding With Proton Pump Inhibitor Therapy in Acute Venous Thromboembolism: Pilot Randomized Study (RADIANT Study)

TypeinterventionalSponsorOttawa Hospital Research InstituteRan2024 to 2028Enrolled360ConditionsVenous Thromboembolism, Gastro Intestinal Bleeding, Blood ClotArmsOmeprazole 20 mg Oral Tablet, Placebo
3 · Its place in the literature

Who cites it

330 citing papers in PubMed, 18 syntheses or guidelines pooled it, 929 citations in OpenAlex.

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  10. 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
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  13. Direct oral anticoagulants for venous thromboembolism in cancer patients: a systematic review and network meta-analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022
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270 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 13 institutions in 8 countries.

Stuart J ConnollyFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Mark CrowtherFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
John W EikelboomFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
C Michael GibsonFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
John T CurnutteFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
John H LawrenceFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Patrick YueFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Michele D BronsonFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Genmin LuFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Pamela B ConleyFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Peter VerhammeFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Jeannot SchmidtFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Saskia MiddeldorpFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Alexander T CohenFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Jan Beyer-WestendorfFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Pierre AlbaladejoFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Jose Lopez-SendonFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Andrew M DemchukFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Daniel J PallinFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Mauricio ConchaFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Shelly GoodmanFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Janet LeedsFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Sonia SouzaFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Deborah M SiegalFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Elena ZotovaFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Brandi MeeksFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Sadia AhmadFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Juliet NakamyaFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Truman J MillingFrom the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); 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.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
ANNEXA-4 Investigators
Portola Pharmaceuticals (United States) · USMcMaster University · CAPopulation Health Research Institute · CAAcademic Medical Center · NLBaim Institute for Clinical Research · USBrigham and Women's Hospital · USCentre Hospitalier Universitaire de Clermont-Ferrand · FRKU Leuven · BESarasota Memorial Hospital · USSt. Thomas Hospital · CAUniversité Grenoble Alpes · FRUniversity Hospital Carl Gustav Carus · DEUniversity of Calgary · CA

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 is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors.

methodsWe evaluated 352 patients who had acute major bleeding within 18 hours after administration of a factor Xa inhibitor. The patients received a bolus of andexanet, followed by a 2-hour infusion. The coprimary outcomes were the percent change in anti-factor Xa activity after andexanet treatment and the percentage of patients with excellent or good hemostatic efficacy at 12 hours after the end of the infusion, with hemostatic efficacy adjudicated on the basis of prespecified criteria. Efficacy was assessed in the subgroup of patients with confirmed major bleeding and baseline anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.25 IU per milliliter for those receiving enoxaparin).

resultsPatients had a mean age of 77 years, and most had substantial cardiovascular disease. Bleeding was predominantly intracranial (in 227 patients [64%]) or gastrointestinal (in 90 patients [26%]). In patients who had received apixaban, the median anti-factor Xa activity decreased from 149.7 ng per milliliter at baseline to 11.1 ng per milliliter after the andexanet bolus (92% reduction; 95% confidence interval [CI], 91 to 93); in patients who had received rivaroxaban, the median value decreased from 211.8 ng per milliliter to 14.2 ng per milliliter (92% reduction; 95% CI, 88 to 94). Excellent or good hemostasis occurred in 204 of 249 patients (82%) who could be evaluated. Within 30 days, death occurred in 49 patients (14%) and a thrombotic event in 34 (10%). Reduction in anti-factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage.

conclusionsIn patients with acute major bleeding associated with the use of a factor Xa inhibitor, treatment with andexanet markedly reduced anti-factor Xa activity, and 82% of patients had excellent or good hemostatic efficacy at 12 hours, as adjudicated according to prespecified criteria. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327.).

Indexed as

Acute DiseaseAgedAged, 80 and overAtrial FibrillationCoagulantsFactor XaFactor Xa InhibitorsFemaleGastrointestinal HemorrhageHemorrhageHumansIntracranial HemorrhagesMaleRecombinant ProteinsROC CurveCoagulantsFactor XaFactor Xa InhibitorsPRT064445Recombinant Proteins

Identifiers

PMID30730782
PMCPMC6699827
OpenAlexW2914381505

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Registered trials

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.