Disclosures The PREVENT IV Trial was supported by Corgentech and Bristol-Myers Squibb

Transcription

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; 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- Research Grants From Corgentech and Bristol-Myers Squibb,, 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- -Research Grants From Corgentech and Bristol-Myers Squibb, John A. Alexander- None. Also details of other COI information can be obtained at 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 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 Inclusion First CABG Age 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 S-SVG = 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 croportional hazards model. Covariates for composite end-point included age, gender, history of congestive heart failure, recent myocardial infarction (within 30 days), use of IMA conduit and CPB use. For per graft endpoints, general estimating equation techniques were used to adjust for correlation between grafts within a patient. Covariates for graft analysis included weight, duration of surgery, CPB use, harvest technique, target artery quality, and whether graft was a m-svg

9 Results: Types of distal SVG anastomosis 29.8% S-SVG M-SVG M&S-SVG 4.9% 65.3%

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) 64 (56, 71) Female sex 20.9% 22.8% 17.3% <0.001 Race-nonwhite 9.1% 9.1% 9.1% 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% 0.20 Myocardial Infarction 42.2% 42.2% 42.4% 0.90 Renal insufficiency (GFR<60) 2.2% 2.1% 2.2% 0.90 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% <0.001

11 Results: Presenting features Presenting Features Overall No m-svg M-SVG P Heart rate (median [IQR]), bpm 70 (62, 80) 70 (62, 80) 71 (62, 80) SBP (median [IQR]), mmhg 134 (120, 149) 133 (120, 149) 134 (120, 150) DBP (median [IQR]), mmhg 75 (67, 82) 76 (66, 82) 74 (68, 82) Peoperative NYHA Class 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%) 50% (40%, 60%) No of Diseased Vessels >2 or left main (>75% Stenosis) 79.4% 78.3% 81.6% 0.031

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

13 Vein Graft Failure ( 75%) 40% 30% 20% 10% 30.5% 24.1% HR 1.24, 95% CI % 20.8% HR 1.40, 95% CI % m-svg no m-svg m-svg No m-svg Per Graft Per Graft-Good Target Qality

14 SVG Failure (%) SVG Failure rates in Various Groups SVG Failures in Various Groups T-SVG-F s-svg-f m-svg-f Both SVG-F s-svg m+s-svg m-svg

15 5- Year Major Adverse Clinical Events (m-svg vs. s-svg [referent]) Five-year Major Adverse Clinical Events (MACE) Unadj Death/MI/Revasc Adj Death/MI/Revasc Unadj Death/MI Adj Death/MI Unadj Death Adj Death Hazard Ratio (95% CI)

16 MACE (%) 5- Year MACE in Angiographic Cohort Excluding Perioperative MIs 70% 60% 50% 40% 30% 20% 10% HR % 5-year MACE (Death/MI/Revasc) in Angiographic Cohort (Excluding Periop MIs) HR % CI % HR % CI % HR % CI % HR % CI % HR % CI % 0% s-svg/no SVG Fail s-svg/>1 SVG Fail m-svg +/- s- SVG-no SVG Fail m-svg + s- SVG/>1 s-svg Fail-no m-svg Fail m-svg +/-, s- SVG/>1 m-svg Fail m-svg + s- SVG/>1/ both s-svg & m- SVG Fail

17 Strengths 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

18 Conclusions The use of m-svg conduits was associated with a higher rate of vein graft failure and worse 5-year outcomes. The worse outcomes associated with m-svg appear to be related to the overall higher clinical events rates associated with any SVG failure with higher m-svg failure rates translating into poorer outcomes for patients with m-svg. Additional studies are needed to identify why m-svgs appear to have a higher failure rate, including perhaps a more thorough intraoperative evaluation of graft quality to identify the most appropriate conduit to improve long-term graft patency and clinical outcomes in patients undergoing CABG In the meantime, this data should stimulate use of s-svg over m-svg when feasible.