Preservation Solutions, Vein Graft Patency, and Outcomes after Coronary Bypass Surgery

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. 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. Study objective • Observational-comparative effectiveness study that evaluates the effects of vein graft preservation solutions on VGF and clinical outcomes

4. 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 (Edifoligidevs 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. 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. 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. 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, creatinineclearance, endoscopic vein graft harvesting, IMA use, worst target artery quality, worst graft quality, time on cardiopulmonary bypass, peri-index CABG MI

8. Use of preservation solutions N=1,339 N=971 % of patients N=507 SALINE BUFFERED BLOOD

9. Baseline characteristics

10. Procedural characteristics

11. Adverse events through 30 days

12. VGF at 1-year follow-up

13. Death/MI/Revasc 26.5% 25.7% 22.6%

14. Adjusted hazard ratios for 5-yr outcomes

15. 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. 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. Questions?