1. Saphenous Vein Grafts with Multiple Versus Single Distal Targets in Patients Undergoing Coronary Artery Bypass Surgery: One-Year Graft Failure and Five-Year Outcomes from the Project of Ex-vivo Vein Graft Engineering via Transfection (PREVENT)-IV Trial
Rajendra H. Mehta, MD, MS; T. Bruce Ferguson, MD; Renato D. Lopes, MD, PHD; Gail E. Hafley, MS; Michael J. Mack, MD; Nicholas T. Kouchoukos, MD; C. Michael Gibson, MD; Robert A. Harrington, MD; Robert M. Califf, MD; T. Bruce Ferguson, MD; Eric D. Peterson, MD, MPH; John A. Alexander, MD, MS; on behalf of PREVENT-IV Investigators

2. Disclosures
Rajendra H Mehta-None, T. Bruce Ferguson-None, Renato D. Lopes-None; Gail E. Hafley, MS-None, Michael J. Mack, MD-None, Nicholas T. Kouchoukos-None, C. Michael Gibson-None, Robert A. Harrington-Research Grants From Corgentech and Bristol-Myers Squibb, Eric D. Peterson- Research Grants from Merck/Schering Plough, Bristol- Myers Squibb and Society of Thoracic Surgery, Robert M. Califf-None, John A. Alexander-None.
The PREVENT IV Trial was supported by Corgentech and Bristol-Myers Squibb

3. Background
Saphenous vein grafts (SVG) with single proximal and multiple distal anastomosis (m-SVG) are often used during CABG
Advantages of m-SVG versus multiple single SVG (single proximal and distal anastomosis, s-SVG) include
Shorter vein segment allowing bypasses of >1 vessel
Shorter revascularization time because of single proximal anastomosis
Used by many in emergent/salvage/urgent situation and when inadequate vein conduits available for bypass.
Most studies evaluating outcomes of m-SVG versus s-SVG
Single center
No systematic angiographic follow-up
Preceded the era of improved medical therapy

4. Objectives Hypothesis
To assess the patency of m-SVG compared with s-SVG in patients undergoing CABG
To assess the influence of m-SVG use on the short- and long-term (5-year) clinical outcomes in patients undergoing CABG
Hypothesis
The use of m-SVG and s-SVG will have similar 1-year vein graft patency and 5-year clinical outcomes in patients undergoing CABG

5. Study Design & Follow-Up
Enrolled Patients
(n=3014)
EDIFOLIGIDE
(n=1508)
PLACEBO
(n=1506)
Angiography Cohort
(n=1197)
Non-Angiography
(n=311)
Angiography Cohort
(n=1203)
Non-Angiography
(n=303)
1-year Angiographic Endpoint (81%)
1-Year Angiographic Endpoint (79%)
5-Year Clinical Endpoint (99.7%)
5-Year Clinical Endpoint (99.2%)

6. Inclusion / Exclusion Criteria
First CABG
Age 18–80 years
At least 2 planned autogenous vein grafts
Informed Consent (including angio f/u)
Exclusion
Prior CABG or valve surgery
Planned concomitant valve surgery
Vasculitis or hypercoaguable state
Comorbidity making 5-year survival unlikely
Enrollment in another trial w/ Edifoligide or another investigational drug or device

7. Methods Patient Population and Definitions
All patients enrolled in the PREVENT-IV trial
M-SVG = graft with 1 proximal and >1 distal anastomosis
SVG failure was defined as stenosis >75% of at least 1 SVG on follow-up quantitative angiography
Failure of any part of a m-SVG was defined as graft failure

8. Methods Statistical analyses
Covariate adjusted analyses of outcomes (death, MI, revascularization, vein graft failure) were assessed using a Cox proportional hazards model.
Covariates included age, gender, history of congestive heart failure, recent myocardial infarction (within 30 days), status of operation, harvesting technique and use of IMA conduit and CPB.
For per graft endpoints, general estimating equation techniques were used to adjust for correlation between grafts within a patient.
Covariates included weight, duration of surgery, CPB use, harvest technique, target artery quality, vein graft quality and whether graft was a m-SVG or not.

9. Results

10. Results Clinical Characteristics Characteristics Overall (n=3014)
No m-SVG
(n=1969)
m-SVG
(n=1045)
P value
Age, median (IQR), years
64 (56, 71)
63 (56, 70)
0.416
Female sex
20.9%
22.8%
17.3%
<0.001
Race-nonwhite
9.1%
0.285
Medical history
Hypertension
75.1%
74.4%
76.5%
0.20
Diabetes Mellitus
37.8%
36.9%
39.4%
0.18
Current Smoking
22.9%
23.0%
22.7%
0.17
Chronic Lung Disease
15.8%
15.6%
16.1%
0.73
Preoperative A Fibrillation
7.0%
6.6%
7.8%
Myocardial Infarction
42.2%
42.4%
0.90
Renal insufficiency (GFR<60)
2.2%
2.1%
Congestive Heart Failure
9.7%
9.5%
10.0%
0.72
Prior stroke
5.5%
5.8%
4.9%
0.30
Peripheral Vascular Disease
12.2%
12.0%
12.6%

11. Results: Presenting features
Overall
No m-SVG
M-SVG P
Heart rate (median [IQR]), bpm
70 (62, 80)
71 (62, 80)
0.222
SBP (median [IQR]), mmHg
134 (120, 149)
133 (120, 149)
134 (120, 150)
0.276
DBP (median [IQR]), mmHg
75 (67, 82)
76 (66, 82)
74 (68, 82)
0.029
Peoperative NYHA Class
0.374 I
40.2%
40.7%
37.3% II
33.4%
33.3%
33.8%
III
18.0%
17.9%
18.8% IV
8.4%
8.1%
10.2%
LVEF, median (IQR)
50% (40%, 60%)
50% (42%, 60%)
0.018
No of Diseased Vessels >2 or left main (>75% Stenosis)
79.4%
78.3%
81.6%
0.031
Reformat
Are you sure this is worth including. Number of diseased vessels is the only interesting finding.

12. Results: Surgical Characteristics Characteristics Overall No m-SVG
P value
IMA Graft
92.5%
95.7%
89.9%
<0.001
Surgery Duration, median (IQR), min
231 (193, 272)
226 (190, 267)
237 (201, 280)
Cardiopulmonary Bypass
78.9%
74.7%
86.8%
Duration of Cardiopulmonary Bypass, median (IQR), min
100 (79, 123)
97 (77, 121)
104 (82, 127)
Postoperative Duration, median (IQR)
Ventilator, hrs
8 (5, 14)
7 (5, 13)
0.025
ICU stay, hrs
26 (22, 47)
26 (22, 48)
0.674
Hospital Stay, days
6 (5, 8)
0.524
Poor Target Artery Quality
21.2%
21.9%
19.6%
0.296
Reformat

13. Vein Graft Failure (≥ 75%)
HR 1.24,
95% CI
HR 1.40,
95% CI
Do you need this?
m-SVG no m-SVG m-SVG No m-SVG

14. SVG Failure rates in Various Groups
Reformat. would remake the figure in powerpoint. Its easy to do and will look better.
There is a typo in “Both “SBG”-F”.
This will take some work to explain. Key is that it is per-patient SVG failure.

15. 5- Year Major Adverse Clinical Events (m-SVG vs. s-SVG [referent])

16. 5- Year MACE in Angiographic Cohort Includes Perioperative MIs
I would redraw this figure in powerpoint.
I might be clearer if switched bar 2 and 3.
This will take some explaining.

17. 5- Year MACE in Angiographic Cohort Excluding Perioperative MIs
Results are the same w or w/o peri-op MI. I would only show 1. Probably w/o peri-op MI.

18. 4- Year MACE (Death/MI/Revasc) Rates in Angiographic Cohort (Excluding All Events Before Angiogram).
Results are the same w or w/o peri-op MI. I would only show 1. Probably w/o peri-op MI.

19. Strengths Limitations
First study to prospectively collect not only clinical but also angiographic data.
Limitations
Non-randomized, retrospective analysis of the PREVENT IV data limiting inference regarding causation.
Small number of patients with isolated m-SVGs or m-arterial grafts (consistent with contemporary practice).
No differentiation possible between ‘Y’ vs. ‘Sequential’ anastomosis of m-SVG.
Only patients undergoing first CABG in PREVENT-IV

20. Conclusions
The use of m-SVG conduits was associated with a higher rate of vein graft failure and worse 5-years outcomes.
The worse outcomes associated with m-SVG appeared to be related to the worse outcomes associated with any SVG failure, thus higher m-SVG failure rates translated into poorer outcomes for patients who received m-SVGs.
This data should stimulate the use of s-SVG over m-SVG when feasible.
Additional studies are needed to identify the most appropriate conduit and strategies to improve long-term graft patency of both m- and s- SVG as well as for improving the overall clinical outcomes in patients undergoing CABG.