Vein Graft Failure Following Coronary Artery Bypass Surgery: Does it Matter?

1. Vein Graft Failure Following Coronary Artery Bypass Surgery: Does it Matter? Renato D. Lopes • John H. Alexander • Rajendra H. Mehta • Gail E. Hafley • Michael J. Mack • Keith B. Allen • Eric D. Peterson • Robert A Harrington • C. Michael Gibson • Robert M. Califf • Nicholas T. Kouchoukos • T. Bruce Ferguson - ACC- Atlanta, 2010 -

2. Disclosures None of the authors has any disclosures related to this study

3. Background • Saphenous vein grafts (SVG) are the most common conduit used in coronary artery bypass graft (CABG) surgery • Per patient rates of vein graft failure (VGF): 25-45% • Depends on: • Population • When measured • How defined Alexander JH. JAMA 2005; 16;294(19):2446-2454 Widimsky P. Circulation 2004 30;110(22):3418-3423

4. Vein Graft Failure Pathogenesis of VGF Intimal injury Smooth muscle migration Neointimal hyperplasia Atherosclerosis Thrombosis

5. Background Cataldo G,Circulation 2003 Roth JA, Ann Thorac Surg 1979 Shah PJ. J Thorac Cardiovasc Surg 2003 • Predictors of Vein Graft Failure: • Location • Diameter • Quality • Number of anastomoses • Time since implantation of the SVG native target vessel

6. Background • Little is know about the relationship between vein graft failure and subsequent clinical outcomes

7. Objectives • To assess long-term (5 years) clinical outcomes of patients enrolled in the PREVENT-IV trial • To assess the relationship between vein graft failure assessed by coronary angiography 12-18 months post-CABG and 5-year clinical outcomes

8. Enrolled Patients (n=3014) PREVENT-IVStudy Design & Follow-Up 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 (N=1430, 94.8%) 5-year Clinical Endpoint (N=1435, 95.3%)

9. Methods • We assessed the long-term clinical outcomes of patients enrolled in the PREVENT-IV trial • Follow-up was performed by mail or telephone survey • Clinical outcomes included death, MI, and repeat revascularization through 5 years • All events were confirmed by review of medical records

10. Methods • Vein graft failure was assessed by quantitative coronary angiography and defined as a ≥75% stenosis anywhere in the vein graft • Vein graft failure was classified both per patient and per graft • Patients who had clinical events or died before angiographic follow-up were excluded from these analyses

11. Statistical Analysis • Cumulative event rates for clinical outcomes were calculated using the Kaplan-Meier method • Covariate adjusted analyses of outcomes were assessed using the Cox proportional hazards model • Logistic regression was used to assess per patient graft failure outcomes

12. Statistical Analysis • Individual graft failure rates were adjusted for intrapatient correlation using general estimating equation techniques • The Cox proportional hazards model (with covariates for the number of grafts implanted and the proportion failed) was used to assess the relationship between graft failure and clinical outcomes

13. Time to 1-Year AngiogramAngiography Cohort Alexander JH. JAMA 2005; 16;294(19):2446-2454

14. Death, MI, or Revascularization 0.3 0.2 Event Rate 0.1 0.0 0 1 2 3 4 5 Years Edifoligide HR 1.03 (95% CI: 0.89-1.18) Placebo

15. Death or MI 0.3 0.2 Event Rate 0.1 0.0 0 1 2 3 4 5 Years From Angiogram Edifoligide HR 1.01 (95% CI: 0.83-1.23) Placebo

16. 0.3 0.2 Event Rate 0.1 0.0 0 1 2 3 4 5 Years Death Edifoligide HR 1.10 (95% CI: 0.89-1.36) Placebo

17. Results: VGF and Outcomes • The composite of death, MI, or revascularization occurred more frequently among patients who had vein graft failure compared with those who had did not Adjusted HR 1.79, 95% CI 1.40-2.28; P<0.001 • There was no relationship between vein graft failure and death / MI or death in either per patient or per graft analyses

18. 0.3 0.2 Event Rate 0.1 0.0 0 1 2 3 4 Years From Angiogram Post Angiogram Events HR 1.79, 95% CI 1.40-2.28; P<0.001 NS

19. Vein Graft Failure and Outcomes“Subgroups” There was no impact on the relationship between vein graft failure and 5-year clinical outcomes based on: • Graft Target (LAD vs other) • Target Artery Quality (Good vs other) • Graft Quality (Good vs other) • IMA Failure (Yes vs no)

20. Limitations • A causal relationship between vein graft failure and clinical outcomes cannot be proven. We assessed only associations • Angiographic follow-up was protocol driven and may have influence revascularization rates

21. Conclusions • Vein graft failure 1 year after CABG is strongly associated with an increased risk of death, MI, or revascularization at 5 years • This association is driven by early revascularization with no association between vein graft failure and death or MI • Further investigation of the appropriate management of patients with angiographic VGF post-CABG is needed

22. Thank you

23. Back up slides

24. MI Prior to 1-Year Angiogram 0.06 0.05 0.04 Event Rate 0.03 0.02 0.01 0.00 0 2 4 6 8 10 12 Months From Enrollment Vein Graft Failure No Vein Graft Failure

25. Revascularizations Prior to 1-Year Angiogram 0.06 0.05 0.04 Event Rate 0.03 0.02 0.01 0.00 0 2 4 6 8 10 12 Months From Enrollment Vein Graft Failure No Vein Graft Failure