ISAR-CABG: Randomized, Superiority Trial of Drug-Eluting-Stent and Bare Metal Stent in Safenous Vein Graft Lesions

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1 ISAR-CABG: Randomized, Superiority Trial of Drug-Eluting-Stent and Bare Metal Stent in Safenous Vein Graft Lesions J. Mehilli, MD, G. Richardt, F-J. Neumann, S. Massberg, K-L. Laugwitz, J. Pache, J. Hausleiter, I. Ott, M. Fusaro, T. Ibrahim, S. Schulz, R. A. Byrne, A. Schömig, A. Kastrati Deutsches Herzzentrum & 1st Med. Klinik rechts der Isar, Technische Universität Munich, Germany

2 Disclosure Statement of Financial Interest Lecture fees from Abbott Vascular

3 Background are more effective and as safe as their predecessors in native coronary artery lesions Trials, 4958 pts HR 0.43 (0.34, 0.54) 5 Trials, 3513 pts HR 0.46 (0.38, 0.55) Probability of Death, MI and Reintervention, % Years After Randomization Patients at Risk SES Sirolimus-eluting stent Bare metal stent Kastrati Schömig, NEJM 07 Stone Leon, NEJM 07

4 vs. in Saphenous Vein Graft Lesions Survival DELAYED RRISC Trial N=75 TLR 50 % 40 P= months 0 SES Vermeersch et al., JACC 07

5 vs. in Saphenous Vein Graft Lesions SOS Trial N=80 All-cause Death Target Lesion Revascularization Cardiac death 7% (PES) vs. 13% () HR 0.62 [ ]; P=0.51 Brilakis et al., JACC Intv 11

6 Objective of the of ISAR-CABG Trial: to compare the efficacy of drug-eluting stents against bare metal stents in a trial powered for clinical events Participating Centers Deutsches Herzzentrum Munich 1. Med. Klinik, Klinikum rechts der Isar, Munich Herzzentrum Bad Krozingen, Bad Krozingen Bad Segeberger Kliniken, Bad Segeberg Germany

7 Patient Selection Inclusion criteria Patients with ischemic symptoms or evidence of myocardial ischemia in the presence of 50 % de novo stenosis located in saphenous vein grafts Informed, written consent Exclusion criteria Cardiogenic shock Target lesion located in arterial grafts Malignancies with life expectancy <1 year Allergies to study medication

8 Primary Endpoint Composite of death, myocardial infarction ischemia-related target lesion revascularization at 1-year post index PCI

9 Secondary Endpoints All cause mortality Myocardial infarction Ischemia-related target lesion revascularization Incidence of definite/probable stent thrombosis at 1-year post index PCI

10 Sample Size Calculation Hypothesis: Drug-eluting stent () is superior to bare metal stent () in terms of major adverse cardiac events Assumptions: Incidence of primary endpoint in group of 30% Reduction of MACE with of 33% Power of 80% -level of 0.05 Total number of patients needed: 600 (accounting for possible losses at follow-up)

11 ISAR-CABG Is Drug-Eluting Stenting Associated With Improved Results in Coronary Artery Bypass Grafts? 610 patients with de novo SVG lesions (Cypher/Taxus/BP Sirolimus) n=303 n=307 6 to 8-month repeat angiogram (encouraged) 12-month clinical follow-up

12 Follow-Up Protocol 600 mg Clopidogrel PCI ASS 500 mg 0 30 d 6-8 mo. 12 mo. serial CK + CKMB measurements clinical follow-up repeat angiography clinical follow-up Clopidogrel Aspirin 2x75 mg/day until discharge 75 mg at least 6 months after index PCI 0 mg/d indefinitely

13 Baseline clinical characteristics n=303 n=307 Age, years 71.4± ±9.3 Female, % Art. hypertension, % Diabetes, % Current smoker, % 8 6 Hyperlipidemia, % SVG age, years 13.8± ±5.1 History of MI, % 56 55

14 Baseline clinical characteristics, II n=303 n=307 Clinical presentation, % acute MI unstable angina stable angina Multivessel disease, % Multilesion PCI, % >1 SVGs treated/patient, % LV ejection fraction, % 49.2± ±13.8

15 Angiographic characteristics n=386 n=385 Recipient vessel, % LAD/diagonal LCx/marginal RCA/PDA Vessel size, mm 3.36± ±0.73 Total stented length, mm 26.8± ±17.7

16 Distribution of SVG Degeneration Score % %

17 Distribution of Lesion Location within the SVGs aortal coronary proximal medial distal diffuse % %

18 Distribution of TIMI Flow Rates Prior to PCI After PCI % % TIMI 3 TIMI 2 TIMI 1 TIMI 0

19 30-Day Clinical Outcomes % P=.57 P=.66 P=.07 P= All-cause death Cardiac death Myocardial infarction MACE* * No TLR occurred and only 1 pt () died suddenly (probable stent thrombosis) during 30-day follow-up

20 Primary Endpoint: Death/MI/TLR 50 Cumulative Incidence (%) P=.03 RR 0.65 [ ] 22.1% 15.4% Months After Randomization

21 All-cause Death 50 Cumulative Incidence (%) P=.82 RR 1.09 [ ] 5.2% 0 4.7% Months After Randomization

22 Myocardial Infarction Cumulative Incidence (%) P=.27 RR 0.66 [ ] 6.0% Months After Randomization 4.2%

23 Death or Myocardial Infarction 50 Cumulative Incidence (%) P=.27 RR 0.75 [ ] 10.9% 8.5% Months After Randomization

24 Definite/Probable Stent Thrombosis 5 Cumulative Incidence (%) P=.99 RR 1.01 [ ] 0.7% 0.7% Months After Randomization

25 Target Lesion Revascularization 50 Cumulative Incidence (%) P=.02 RR 0.52 [ ] 13.1% 0 7.2% Months After Randomization

26 Target Vessel Revascularization TLR % P=.02 RR 0.52 [ ] TVR % P=.03 RR 0.61 [ ]

27 Summary Out to 12 months drug-eluting stents are superior to bare metal stents in a large-scale study powered for clinical endpoints. The need for repeat revascularizations was reduced by ~50% with as compared to. were comparable to regarding safety parameters stent thrombosis, death or MI.