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The withdrawal of aprotinin: Why? how and what alternatives? Volume 21, issue 2, Février 2009

Author
Service d’Anesthésie-Réanimation Chirurgicale, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Université Paris Descartes, 27, rue du Fbg Saint-Jacques 75014 Paris

The marketing autorisation for aprotinin, a prohemostatic drug widely used to reduce blood loss and blood transfusion in surgery, has recently been suspended. This decision has been triggered by studies raising safety concerns in adult cardiac surgery, and particularly the early termination of the large Canadian BART trial after a preliminary analysis showing an increased mortality, 30 days after surgery, in the group of patients receiving aprotinin as compared with the group receiving alternative antifibrinolytics. Such data surprisingly contradict the reassuring conclusions of previous meta-analyses of randomised controlled trials. Moreover, they challenge the cursory assumption that the undisputed blood-sparing efficacy of aprotinin in cardiac surgery may be immediately translated into a global benefit.The conclusions of the BART trial leave us with many unanswered questions, particularly regarding aprotinin safety in other procedures and populations (pediatric). However, the aprotinin story illustrates the importance of relying on studies adequately tailored to assess the risk-benefit ratio, and not only the blood-sparing efficacy, before integrating a hemostatic agent into clinical use. The improper use of exposure to blood transfusion as a surrogate marker of mortality and morbidity also gives food for thought. The only alternative to aprotinin presently available in France is tranexamic acid. The prophylactic use of this agent has been shown to be efficacious in various surgical procedures. However, a full risk-benefit analysis in a wide spectrum of settings is required.