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

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

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


Study objective

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


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


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)


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


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


Use of preservation solutions

Series10

5

10

15

20

25

30

35

40

45

50N=1,339

N=971

N=507

SALINE BUFFERED BLOOD

% o

f pa

tient

s


Baseline characteristics

Saline Buffered Blood P

Age 63 (56, 71) 62 (55, 69) 64 (56, 71) 0.05

Female 21 19 25 0.67

White 92 91 91 0.60

BMI 29 (26, 33) 29 (26, 33) 29 (26, 32) 0.82

Diabetes 38 36 37 0.55

Prior MI 43 43 42 0.83

Renal failure 2 2 2 0.66

Hypercholesterolemia 74 80 77 0.03

Ejection fraction 50 (40, 60) 51 (40, 60) 50 (40, 60) 0.25


Procedural characteristics


Use of CPB 73 85 83 <0.001

IMA graft use 92 95 92 0.09

Endoscopy use 58 67 56 <0.001

>1 distal target 33 25 41 <0.001

Poor target artery 21 26 19 <0.001

Poor vein graft 4 8 5 <0.001

Surgery duration 231 (194,271) 239 (205,275) 227 (187,270) 0.003

CPB duration, min 100 (82,124) 104 (81,123) 97 (75,121) 0.002


Adverse events through 30 days


Stroke 1.6 1.8 1.2 0.65

Re-OR for bleeding 2.8 2.8 2.1 0.53

Atrial fibrillation 26.0 24.9 27.4 0.55

Renal failure 3.2 3.0 3.6 0.78

Mediastinitis 0.5 1.0 0.7 0.54

ARDS 0.8 0.6 1.2 0.41

Peri-index CABG MI 90.6 91.9 89.3 0.25

Repeat CABG 0.1 0.4 0.0 0.13

PCI 0.5 0.0 0.1 0.13


VGF at 1-year follow-up


Death/MI/Revasc

0 1 2 3 4 50%

5%

10%

15%

20%

25%

30%Saline

Buffered

Blood

Years

Eve

nt

Rat

e

1213 1089 1042 995 937

466 432 404 389 370

888 813 757 718 683

26.5%25.7%

22.6%


Adjusted hazard ratios for 5-yr outcomes

Death, MI, or Revasc Death or MI Death

HR 95%-CI P HR 95%-CI P HR 95%-CI P

Buffered vs Saline

0.81 0.64-1.02 0.08 0.85 0.61-1.17 0.31 0.78 0.54-1.11 0.17

Buffered vs Blood

0.81 0.63-1.03 0.09 0.93 0.66-1.30 0.68 0.90 0.62-1.31 0.59

Blood vs Saline

1.00 0.84-1.19 0.98 0.91 0.71-1.16 0.43 0.86 0.66-1.13 0.28


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


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


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