Aprotinin: 1 year on

The nonspecific protease inhibitor aprotinin has been used successfully to reduce bleeding in cardiac surgery. Recent investigations have questioned its safety, and aprotinin has finally been withdrawn from marketing after a large prospective study demonstrated a trend toward higher mortality.

The initial studies of Karkouti and Mangano provoked a considerable number of large-scale investigations focusing on the safety issues of aprotinin. These studies were of retrospective nature and used sophisticated statistical methods to overcome a possible selection bias. Recently, aprotinin was predominantly used in patients with a higher risk of bleeding, which hampers a retrospective comparison with patients without the drug. This review summarizes the diverging results of these studies.

It remains a matter of speculation whether the quality and results of published data justify the withdrawal of aprotinin; however, one has to accept that this drug is no longer available. It is clear from the aprotinin story that there are no effective instruments to control the safety and clinical efficacy of a drug after its regulatory approval. This highlights the urgent need for independent clinical safety studies after the formal registration of a drug.