Benefits of aprotonin outweigh risks in high-risk cardiac surgery patients

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Benefits of aprotonin outweigh risks in high-risk cardiac surgery patients
MedWire News:

Aprotonin for preventing major blood loss after cardiac surgery has a better risk–benefit profile than tranexamic acid in high-risk, but not low-to-moderate risk patients, study findings show.

“Its use in high-risk cases may therefore be warranted,” say Keyvan Karkouti, from Toronto General Hospital in Ontario, Canada, and team in the journal Anesthesia and Analgesia.

The marketing approval for aprotonin was withdrawn in Europe and placed under severe restrictions in North America following recent research that found patients receiving the antifibrinolytic drug had higher morbidity and mortality than patients receiving lysine analogues.

But Karkouti and colleagues note that very little of the current data pertain to the use of aprotonin in high-risk cases, for whom the benefits of the drug are most likely to outweigh the risks.

To determine whether the risk profile of aprotonin differs according to whether a cardiac patient is low-, moderate-, or high-risk, the team assessed in-hospital mortality, morbidity, and blood loss in 15,375 individuals undergoing cardiopulmonary bypass surgery. Of these, 1017 were given aprotinin (6 X 106 U) and 14,358 were given tranexamic acid (50–100 mg/kg).

The researchers then created a matched-pairs cohort based on propensity scores comprising 772 patients in each treatment group.
Aprotonin treatment was only significantly associated with increased acute injury, with patients taking the drug 1.5 times more likely to experience a more than 50% decrease in estimated glomerular filtration or dialysis than patients receiving tranexamic acid, at rates of 13.5% versus 9.2%.

The researchers note, however, that the risk status of the patients influenced the effects of aprotonin.

In low-to-moderate risk patients, the drug was associated with a higher rate of adverse events than tranexamic acid.

But in high-risk patients, who were in the top 25th percentile of the matched group, aprotonin treatment was associated with fewer cases of massive blood loss and lower adverse event rates compared with tranexamic acid treatment.

These high-risk patients are those who are “undergoing emergency, complex procedures that require prolonged cardiopulmonary bypass support, and they constitute approximately 10% of the general cardiac surgery population,” say Karkouti et al.

“This finding is highly relevant because neither the US Food and Drug Administration nor Health Canada has made a final determination on the status of aprotonin,” they conclude.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009.


Karkouti K, Wijeysundera DN, Yau TM, et al. The risk-benefit profile of aprotinin versus tranexamic acid in cardiac surgery. Anesth Analg 2009; Advance online publication.