title: 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.
abstract: 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: Division of Cardiac Surgery, Department of Surgery, University of Maryland Medical System, Baltimore, Maryland, USA.
authors: Michael C
authors: MC
authors: Grant
authors: Zachary
authors: Z
authors: Kon
authors: Ashish
authors: A
authors: Joshi
authors: Eric
authors: E
authors: Christenson
authors: Seeta
authors: S
authors: Kallam
authors: Nicholas
authors: N
authors: Burris
authors: Junyan
authors: J
authors: Gu
authors: Robert S
authors: RS
authors: Poston
mesh_terms: D007611:Aprotinin / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001780:Blood Coagulation Tests; D047549:Coronary Artery Bypass, Off-Pump; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D006801:Humans; D010979:Platelet Function Tests; D011183:Postoperative Complications; D011446:Prospective Studies; D013927:Thrombosis / Q000209:etiology*
chemical_list: D006490:Hemostatics; D007611:Aprotinin