1. Preservation Solutions, Vein Graft Patency, and Outcomes after Coronary Bypass Surgery RE Harskamp, JH Alexander, PJ Schulte, CM Brophy, MJ Mack, ED Peterson, JB Williams, CM Gibson, RM Califf, NT Kouchoukos, RA Harrington, TB Ferguson Jr, RD Lopes

2. All Rights Reserved, Duke Medicine 2007 Background Vein graft failure (VGF) is an important limitation to the benefits of CABG surgery Much effort is put in methods to minimize trauma and ischemia caused by vein graft handling Ex vivo and animal studies suggest intraoperative storage in solutions that mimic human plasma and have buffer capacity may better preserve functionality Intraoperative graft preservation solutions have not been investigated in recent clinical studies

3. All Rights Reserved, Duke Medicine 2007 Study objective Observational-comparative effectiveness study that evaluates the effects of vein graft preservation solutions on VGF and clinical outcomes

4. All Rights Reserved, Duke Medicine 2007 Study population 3,014 patients of the PREVENT-IV trial database (107 US sites, 2002, 2003) Isolated CABG with at least 2 planned vein grafts First 2,400 ptns planned for 1-yr angiographic f/u Main findings of the trial (Edifoligide vs placebo) were neutral (patient level graft failure OR: 0.96, 0.80-1.14) All other drugs and solutions were left to the operator’s discretion

5. All Rights Reserved, Duke Medicine 2007 Groups and Outcomes Comparison groups * –Saline –Buffered –Blood Outcomes of Interest –VGF at 1-year (ptns: 1,828; grafts: 4,343) ≥75% stenosis (angiographic core lab) –Clinical outcomes (n=3,014) Event adjudication by CEC (>95% completed) * Other base solutions were excluded from analysis (n=196)

6. All Rights Reserved, Duke Medicine 2007 Statistical analysis (1/3) VGF –Patient level analysis Logistic regression Percentage stenosis of the worst graft was used –Graft level analysis Logistic regression GEE for correlation among grafts within individuals –Adjusted for: Weight, duration of surgery, use of endoscopic harvesting, quality of target artery, use of composite graft, use of cardiopulmonary bypass

7. All Rights Reserved, Duke Medicine 2007 Statistical analysis (2/3) Clinical outcomes –Kaplan-Meier curves –Cox-proportional hazard regression –Adjusted for: Age, sex, ejection fraction, prior heart failure, diabetes, chronic lung disease, atrial fibrillation, MI <30 days, creatinine clearance, endoscopic vein graft harvesting, IMA use, worst target artery quality, worst graft quality, time on cardiopulmonary bypass, peri-index CABG MI

8. All Rights Reserved, Duke Medicine 2007 Use of preservation solutions N=1,339 N=971 N=507 SALINE BUFFERED BLOOD % of patients

9. All Rights Reserved, Duke Medicine 2007 Baseline characteristics SalineBufferedBloodP Age63 (56, 71)62 (55, 69)64 (56, 71)0.05 Female2119250.67 White9291 0.60 BMI29 (26, 33) 29 (26, 32)0.82 Diabetes3836370.55 Prior MI43 420.83 Renal failure2220.66 Hypercholesterolemia7480770.03 Ejection fraction50 (40, 60)51 (40, 60)50 (40, 60)0.25

10. All Rights Reserved, Duke Medicine 2007 Procedural characteristics SalineBufferedBloodP Use of CPB738583<0.001 IMA graft use9295920.09 Endoscopy use586756<0.001 >1 distal target332541<0.001 Poor target artery212619<0.001 Poor vein graft485<0.001 Surgery duration231 (194,271)239 (205,275)227 (187,270)0.003 CPB duration, min100 (82,124)104 (81,123)97 (75,121)0.002

11. All Rights Reserved, Duke Medicine 2007 Adverse events through 30 days SalineBufferedBloodP Stroke1.61.81.20.65 Re-OR for bleeding2.8 2.10.53 Atrial fibrillation26.024.927.40.55 Renal failure3.23.03.60.78 Mediastinitis0.51.00.70.54 ARDS0.80.61.20.41 Peri-index CABG MI90.691.989.30.25 Repeat CABG0.10.40.00.13 PCI0.50.00.10.13

12. All Rights Reserved, Duke Medicine 2007 VGF at 1-year follow-up

13. All Rights Reserved, Duke Medicine 2007 Death/MI/Revasc 121310891042995937 466432404389370 888813757718683 26.5% 25.7% 22.6%

14. All Rights Reserved, Duke Medicine 2007 Adjusted hazard ratios for 5-yr outcomes Death, MI, or RevascDeath or MIDeath HR95%-CIPHR95%-CIPHR95%-CIP Buffered vs Saline 0.810.64-1.020.080.850.61-1.170.310.780.54-1.110.17 Buffered vs Blood 0.810.63-1.030.090.930.66-1.300.680.900.62-1.310.59 Blood vs Saline 1.000.84-1.190.980.910.71-1.160.430.860.66-1.130.28

15. All Rights Reserved, Duke Medicine 2007 Limitations Retrospective, non-randomized comparison Potential for unmeasured confounding despite proper adjustment Use of pressure-mediated delivery system mandated per protocol, may affect generalizability Total duration of exposure, temperature of solution and differences in distension pressure during flushing were not documented Potential effect of additives to preservation solutions could not be explored because of sample size limitations

16. All Rights Reserved, Duke Medicine 2007 Conclusions Patients undergoing CABG whose vein grafts were preserved in a buffered solution had lower VGF rates and trends toward better long-term clinical outcomes compared to patients whose grafts were preserved in saline or blood-based solutions These hypothesis generating findings may have important implications for the care of patients undergoing CABG and should be further investigated in adequately sized randomized clinical trials

17. All Rights Reserved, Duke Medicine 2007 Questions?