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Safety Concerns Persist About Aprotinin

New, long-term mortality data reinforce safety concerns about using this antibleeding agent during coronary bypass surgery.

Observational studies published in 2006 raised perioperative safety concerns about using aprotinin (Trasylol), an antifibrinolytic serine protease inhibitor, to reduce bleeding risk during coronary artery bypass grafting (CABG). The FDA has since issued a public health advisory on this topic. Now, we have an update on long-term mortality risk with aprotinin from a cohort whose in-hospital outcomes were reported previously (Journal Watch Cardiology Mar 9 2006).

The present analysis focused on 3876 patients (of the original 4374) whose treating centers participated in a 5-year follow-up study. All had undergone CABG and had received aprotinin; a lysine analogue (aminocaproic acid or tranexamic acid); or no antifibrinolytic treatment. Assignment was not randomized. Survival was assessed prospectively at 6 weeks, at 6 months, and then annually.

In multivariable-adjusted analyses, neither lysine analogue was associated with increased mortality risk at 5 years, compared with no antifibrinolytic treatment. However, aprotinin was (odds ratio for death within 5 years, 1.48; 95% CI, 1.19–1.85), even after further adjustment for patients’ likelihood of receiving one treatment rather than another (OR, 1.37; 95% CI, 1.09–1.73). The risk with aprotinin was consistently elevated during the follow-up period.

Comment: Use of aprotinin during CABG was associated with significantly increased risk for death over 5 years of follow-up in real-world settings. An editorialist reminds us that, despite adjustments for potential confounding, observational design limits this study. Still, he acknowledges the findings’ importance in the context of postmarketing surveillance. Pending further FDA evaluation, the bar for using aprotinin as an antibleeding agent during CABG is high, given the availability of lysine analogue alternatives, which were not associated with increased mortality risk.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology February 28, 2007

Citation(s):

Mangano DT et al. Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery. JAMA 2007 Feb 7; 297:471-9.

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Ferguson TB Jr. Aprotinin — Are there lessons learned? JAMA 2007 Feb 7; 297:527-9.

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• Medline abstract (Free)