Document Detail


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.
MedLine Citation:
PMID:  18721566     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 10(6) kallikrein inhibiting units (KIU) loading dose, 0.5 x 10(6) 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.
Authors:
Michael C Grant; Zachary Kon; Ashish Joshi; Eric Christenson; Seeta Kallam; Nicholas Burris; Junyan Gu; Robert S Poston
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  86     ISSN:  1552-6259     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-25     Completed Date:  2008-09-19     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  815-22; discussion 815-22     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiac Surgery, Department of Surgery, University of Maryland Medical System, Baltimore, Maryland, USA.
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MeSH Terms
Descriptor/Qualifier:
Aprotinin / administration & dosage,  adverse effects*,  blood
Blood Coagulation Tests
Coronary Artery Bypass, Off-Pump*
Follow-Up Studies
Glomerular Filtration Rate / drug effects
Hemostatics / administration & dosage,  adverse effects*,  blood
Humans
Platelet Function Tests
Postoperative Complications
Prospective Studies
Thrombosis / etiology*
Grant Support
ID/Acronym/Agency:
R01 HL084080-01A1/HL/NHLBI NIH HHS; R01 HL084080-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hemostatics; 9087-70-1/Aprotinin
Comments/Corrections

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