Prophylactic treatment with aprotinin, a haemostatic antifibrinolytic agent, is indicated to reduce blood loss and blood transfusion in adults with a high risk of major bleeding undergoing primary or repeat isolated coronary artery bypass graft (CABG) with cardiopulmonary bypass. Overall, aprotinin was consistently more effective than tranexamic acid, ε-aminocaproic acid, desmopressin and placebo in reducing massive blood loss, the need for transfusions of blood products, and the need for reoperation due to diffuse bleeding in trials in this patient population, and was generally well-tolerated. The approval of aprotinin in the EU was reinstated by the European Medicines Agency (EMA) in 2012, following subsequent analysis of the clinical data that led to its suspension in 2007. The EMA analysis concluded that the reduction in massive bleeding provided by aprotinin in patients undergoing isolated CABG is clinically relevant, as it reduces complications, the need for blood product transfusions and the length of hospital stay, without increasing mortality. The relaunch of aprotinin was accompanied by a risk management to assess the pattern of use and safety of aprotinin in clinical practice. Data from centres enrolled in the Nordic Aprotinin Patient Registry are being collected and will be assessed in the final report.
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The manuscript was reviewed by: P. Meybohm, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany; M.A.N.V.P. Morgado, CICS-UBI Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal; K. Zacharowski, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. During the peer review process, Nordic Group, the marketing-authorization holder of aprotinin, was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made based on their scientific and editorial merit.
The preparation of this review was not supported by any external funding.
Conflict of interest
K.A. Lyseng-Williamson is an employee of Adis International Ltd/Springer Nature and the Editor of Drugs & Therapy Perspectives, and has no other conflicts of interest to declare. The Editor of D&TP was not be involved in any publishing decisions for the manuscript.
Enhanced material for this Adis Drug Q&A can be found at https://doi.org/10.6084/m9.figshare.9905507.
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Lyseng-Williamson, K.A. Aprotinin in adults at high risk of major blood loss during isolated CABG with cardiopulmonary bypass: a profile of its use in the EU. Drugs Ther Perspect 36, 1–11 (2020). https://doi.org/10.1007/s40267-019-00690-0