In January 2006, we published an article by Mangano and colleagues1that reported the results of an observational study of antifibrinolyticagents to control bleeding in cardiac surgery. The data suggestedthat patients treated with aprotinin, as compared with no antifibrinolyticagent, aminocaproic acid, or tranexamic acid, had higher risksof a number of adverse events, including cardiovascular events(myocardial infarction, heart failure, and stroke) and renalfailure requiring dialysis. The study data were from a prospectiveregistry funded by the Ischemia Research and Education Foundation.As detailed by Hiatt in a Perspective article in this issueof the Journal, the Food and Drug Administration (FDA),2 onthe basis of the Mangano article and other data, called a meetingof the Cardiovascular and Renal Drugs Advisory Committee inSeptember to discuss the matter. Dr. Mangano was asked to providehis study data so that the FDA could conduct an independentanalysis. In a letter to the editor in this issue of the Journal,3Dr. Mangano reports that he initially placed restrictions onthe FDA's access to his data. However, he reports that morethan five months ago he offered the FDA unrestricted accessto the data, but the offer was not accepted. As noted in a responsefrom the FDA,4 the agency is now eager to move forward withreplication of the Mangano analysis.
It is not clear why the matter of data reanalysis was not resolvedbefore the advisory committee met in September. If the datareanalysis had been completed and had confirmed the risks associatedwith the use of aprotinin, the action of the committee, whichconcluded that no labeling change was necessary, might havebeen different. Regardless of the reasons for the delay, theMangano data and data from a study commissioned by Bayer thatwere not provided to the advisory committee before its Septembermeeting should be reviewed and the committee reconvened as soonas possible. The goal should be to get a clear picture of potentialadverse drug events of aprotinin from the available data. Withthis information, a course that puts patient safety at the forefrontcan be charted. The sooner this happens, the better.
References
Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med 2006;354:353-365. [Free Full Text]
Hiatt WR. Observational studies of drug safety -- aprotinin and the absence of transparency. N Engl J Med 2006;355:2171-2173. [Free Full Text]
Mangano DT. Judging the safety of aprotinin. N Engl J Med 2006;355:2261-2262. [Free Full Text]
Rieves RD, Weiss KD. Judging the safety of aprotinin. N Engl J Med 2006;355:2262-2262.
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