1. 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 
Michael C. Grant, BS, Zachary Kon, BA, Ashish Joshi, MD, PhD, Eric Christenson, BS, Seeta Kallam, MD, Nicholas Burris, BS, Junyan Gu, MD, PhD, Robert S. Poston, MD 
The Annals of Thoracic Surgery 
Volume 86, Issue 3, Pages (September 2008)
DOI: /j.athoracsur
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

2. Fig 1
Glomerular filtration rate was estimated (eGFR) from the serum creatinine daily prior to hospital discharge in all subjects. While preoperative eGFR was similar between groups, the aprotinin group (∘) showed a significant reduction in GFR on day 2 (*p < 0.04) and day 3 (**p < 0.006) compared with the placebo group (•). Differences between groups resolved by day 5.
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

3. Fig 2
Peak serum aprotinin level was compared to the maximum degree of glomerular filtration rate (GFR) change for days 1 to 5 after off-pump coronary artery bypass. For patients receiving aprotinin, the peak level of aprotinin showed a linear relationship to the decline in GFR (r = 0.47, p < 0.05). Aprotinin-treated patients with acute kidney injury showed significantly higher peak aprotinin levels than patients who maintained normal renal function throughout the course of the study. (KIU = kallikrein inhibiting units.)
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

4. Fig 3
(A) Representative impedance traces obtained during whole blood aggregometry performed on blood obtained from a normal volunteer after the in vitro addition of aprotinin. Without aprotinin added, there was a strong aggregation response to thrombin 1 U/mL, as illustrated by a change in ohms of 12.5 over 6 minutes. No platelet response to thrombin was noted when aprotinin levels ranged from 200 to greater than 300 kallikrein inhibiting units [KIU]/mL. A modest response (ie, 5 ohms at 6 minutes) was noted for aprotinin levels less than 200 KIU/mL. (B) Fibrinolytic capacity was assayed using thrombelastography (TEG) to demonstrate clot lysis in response to a low dose of tissue plasminogen activator (tPA, 40 IU) after the in vitro addition of varying doses of aprotinin (n = 3 per dose). As illustrated in these representative traces, the addition of tPA results in near complete lysis of the clot that formed within the TEG cup in the absence of aprotinin. At aprotinin concentrations greater than 50 KIU/mL, the amplitude of the TEG trace shows very minimal change compared with a TEG trace without tPA added, indicating near complete resistance to fibrinolysis.
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions

5. Fig 4
The combination of graft failure, stroke, myocardial infarction, and death over the first postoperative year was used to generate a composite endpoint, major adverse cardiac, and cerebrovascular events (MACCE). The aprotinin group showed a significant reduction in MACCE after the first year (11.8% vs 34.4% of the placebo patients, p < 0.005), and did not appear to be related to the development of postoperative AKI (hazard ratio [HR] 1.103, 95% CI to 4.906, p = NS). In contrast, the risk of MACCE was increased in the placebo group (hazard ratio 2.871, 95% CI to 5.570, p < 0.01) compared with the aprotinin group, an effect that did not appear to be confined to the perioperative period. (ARD = acute respiratory distress.)
The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur )
Copyright © 2008 The Society of Thoracic Surgeons Terms and Conditions