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Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage.

Stuart J Connolly1, Mukul Sharma1, Alexander T Cohen1

  • 1From the Population Health Research Institute, McMaster University, Hamilton, ON (S.J.C., M.S., M.C., A.T., T.K., L.X., K.T., A.S.), and the Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB (A.M.D.) - both in Canada; Guy's and St. Thomas' Hospital, King's College London (A.T.C.), and Imperial College (R.V.), London, NIHR Biomedical Research Centre and College of Life Sciences, University of Leicester, Leicester (T.G.R.), and Alexion Pharmaceuticals UK, Uxbridge (A.L.) - all in the United Kingdom; the Second Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland (A.C.); the Department of Clinical Sciences Lund, Neurology, Lund University, and the Department of Neurology, Skåne University Hospital, Lund (A.G.L.), and AstraZeneca Biopharmaceuticals Research and Development, Late-stage Development, Cardiovascular, Renal, and Metabolism, Gothenburg (A.H., P.L., M.K., E.E.) - all in Sweden; Vall d'Hebron University Hospital, Barcelona (C.A.M.); Semmelweis University, Budapest, Hungary (D.B.); Sapienza University of Rome, Rome (D. Toni); the Department of Neurology, Inselspital University Hospital and University of Bern, Bern, Switzerland (D.J.S.); Rambam Health Care Campus, Technion, Israel Institute of Technology, Haifa (D. Tanne); the Department of Neurology, Oslo University Hospital, and the Norwegian Air Ambulance Foundation - both in Oslo (E.C.S.); the Second Department of Neurology, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens (G.T.); Copenhagen University Hospital, Bispebjerg Hospital, Copenhagen (H.C.); the Department of Medicine 1, Division "Thrombosis and Hemostasis," University Hospital Dresden, Dresden (J.B.-W.), Alfried Krupp Krankenhaus, Essen (R.V.), the Department of Neurology and Stroke (S.P.) and the Hertie Institute for Clinical Brain Research (S.P.), Eberhard-Karls University, Tübingen, the Department of Neurology, Universitätsklinikum Erlangen, Erlangen (B.K.), and the Department of Neurology, Heidelberg University Hospital, Heidelberg (C.G.) - all in Germany; the Department of Neurology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam (J.M.C.), and Radboud University Medical Center, Nijmegen (S.M.) - both in the Netherlands; University Hospitals Leuven, University of Leuven (P.V.), the Department of Neurosciences and Experimental Neurology, KU Leuven (R.L.), and the Department of Neurology, University Hospitals Leuven (R.L.) - all in Leuven, Belgium; Bichat Claude-Bernard Hospital, Paris (P.A.); Turku University Hospital, Turku, Finland (R.O.R.); Tomas Bata Regional Hospital, Zlín, Czech Republic (R.M.); Dell Medical School, University of Texas, Austin, and the University of Houston, Houston (T.J.M.); University of Porto, Porto, Portugal (V.T.-C.); and Hospital of St. John of God, Sigmund Freud University, Medical Faculty, Vienna (W.L.).

The New England Journal of Medicine
|May 15, 2024
PubMed
Summary

Andexanet alfa improved control of hematoma expansion in patients with intracerebral hemorrhage taking factor Xa inhibitors. However, this reversal agent was linked to an increased risk of thrombotic events, including ischemic stroke.

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Area of Science:

  • Neurology
  • Hematology
  • Pharmacology

Background:

  • Patients with acute intracerebral hemorrhage (ICH) on factor Xa inhibitors face a risk of hematoma expansion.
  • The efficacy of andexanet alfa, a reversal agent for factor Xa inhibitors, in mitigating hematoma expansion in ICH is not well-established.

Purpose of the Study:

  • To evaluate the effect of andexanet alfa compared to usual care on hematoma expansion in patients with acute ICH who have taken factor Xa inhibitors.

Main Methods:

  • A randomized trial assigned patients (within 15 hours of ICH onset) to andexanet alfa or usual care.
  • Primary endpoint: hemostatic efficacy (hematoma expansion ≤35%, NIHSS score increase <7, no rescue therapy).
  • Safety endpoints included thrombotic events and death.

Main Results:

  • Hemostatic efficacy was achieved in 67.0% with andexanet alfa vs. 53.1% with usual care (P=0.003).
  • Andexanet alfa significantly reduced anti-factor Xa activity (94.5% vs. 26.9%, P<0.001).
  • Thrombotic events occurred in 10.3% with andexanet alfa vs. 5.6% with usual care (P=0.048), including ischemic strokes (6.5% vs. 1.5%).

Conclusions:

  • Andexanet alfa demonstrated superior control of hematoma expansion in ICH patients on factor Xa inhibitors compared to usual care.
  • The use of andexanet alfa was associated with an increased incidence of thrombotic events, notably ischemic strokes.
  • While effective in hemostasis, the prothrombotic risk necessitates careful consideration in clinical practice.