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Original Articles: Adult Cardiac

Is Aprotinin Safe to Use in a Cohort at Increased Risk for Thrombotic Events: Results From a Randomized, Prospective Trial in Off-Pump Coronary Artery Bypass

^a Division of Cardiac Surgery, Department of Surgery, University of Maryland Medical System, Baltimore, Maryland
^b University of Maryland Baltimore County, Department of Information Systems, Baltimore, Maryland

Accepted for publication April 14, 2008.

^_* Address correspondence to Dr Poston, Division of Cardiac Surgery, Boston University School of Medicine, Robinson 402, 88 E. Newton St, Boston, MA 02118 (Email: robert.poston{at}bmc.org).

Presented at the Forty-fourth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2008.

Background: Multiple randomized trials have established a favorable safety profile for aprotinin use during cardiac surgery, but recent database analyses suggest an increased risk of adverse thrombotic events. Our group previously demonstrated that off-pump coronary artery bypass (OPCAB) is linked to a postoperative hypercoagulable state. In this study, we tested whether aprotinin influences thrombotic events after OPCAB.

Methods: Patients randomly received saline (n = 61) or aprotinin (2 x 10⁶ kallikrein inhibiting units (KIU) loading dose, 0.5 x 10⁶ KIU/hour [n = 59]) during OPCAB. Aprotinin levels (KIU/mL) were analyzed before, and 30 minutes (peak) and 4 hours after the loading dose. Estimated glomerular filtration rate (eGFR) was calculated daily based on Cockcroft equation with acute kidney injury (AKI) defined as eGFR less than 75% of baseline. Major adverse cardiac and cerebrovascular events (MACCE) were monitored during the first year, including acute graft failure by predischarge computed tomographic angiography.

Results: Compared with placebo, the aprotinin group developed a significantly lower eGFR on day 3 (p < 0.006), but this difference resolved by day 5. Peak aprotinin level correlated with the degree of eGFR decline noted on day 3 (r = 0.56, p < 0.03) and independently predicted postoperative AKI (odds ratio 8.8, p < 0.008). The receiver operating characteristic analysis demonstrated that peak aprotinin level strongly predicts AKI (area under the curve = 0.86, 95% confidence interval 0.69 to 1.00). The percentage of patients reaching the composite MACCE endpoint was significantly reduced in the aprotinin versus placebo group (12 vs 34%, p = 0.01).

Conclusions: Compared with placebo, aprotinin use was associated with less MACCE but more AKI after OPCAB. The strong relationship between the peak aprotinin level and subsequent AKI suggests weight-based protocols for dosing aprotinin may reduce this risk.

This article has been cited by other articles:

				P. H. Desai, D. Kurian, N. Thirumavalavan, S. P. Desai, P. Ziu, M. Grant, C. White, R. C. Landis, and R. S. Poston A Randomized Clinical Trial Investigating the Relationship Between Aprotinin and Hypercoagulabilityin Off-Pump Coronary Surgery Anesth. Analg., November 1, 2009; 109(5): 1387 - 1394. [Abstract] [Full Text] [PDF]