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
Disclosure Statement of Financial Interest Lecture fees from Abbott Vascular
Background are more effective and as safe as their predecessors in native coronary artery lesions 50 14 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, % 0 1 2 3 4 5 Years After Randomization Patients at Risk SES 40 30 10 0 2486 2472 1891 1639 1099 902 921 773 Sirolimus-eluting stent Bare metal stent 682 621 491 395 Kastrati Schömig, NEJM 07 Stone Leon, NEJM 07
vs. in Saphenous Vein Graft Lesions Survival DELAYED RRISC Trial N=75 TLR 50 % 40 P=.55 30 24 30 10 months 0 SES Vermeersch et al., JACC 07
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 [0.15-2-6]; P=0.51 Brilakis et al., JACC Intv 11
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
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
Primary Endpoint Composite of death, myocardial infarction ischemia-related target lesion revascularization at 1-year post index PCI
Secondary Endpoints All cause mortality Myocardial infarction Ischemia-related target lesion revascularization Incidence of definite/probable stent thrombosis at 1-year post index PCI
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)
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
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
Baseline clinical characteristics n=303 n=307 Age, years 71.4±9.0 71.5±9.3 Female, % 13 16 Art. hypertension, % 71 73 Diabetes, % 37 35 Current smoker, % 8 6 Hyperlipidemia, % 88 86 SVG age, years 13.8±5.5 13.5±5.1 History of MI, % 56 55
Baseline clinical characteristics, II n=303 n=307 Clinical presentation, % acute MI 17 13 unstable angina 21 27 stable angina 62 60 Multivessel disease, % 98 99 Multilesion PCI, % 24 22 >1 SVGs treated/patient, % 4.0 3.6 LV ejection fraction, % 49.2±12.2 49.5±13.8
Angiographic characteristics n=386 n=385 Recipient vessel, % LAD/diagonal 32.0 31.0 LCx/marginal 35.0 36.0 RCA/PDA 33.0 33.0 Vessel size, mm 3.36±0.67 3.38±0.73 Total stented length, mm 26.8±15.4 27.5±17.7
Distribution of SVG Degeneration Score 0 1 2 3 % 18 36 19 % 34 26 27
Distribution of Lesion Location within the SVGs aortal coronary proximal medial distal diffuse % 14 4 16 17 6 18 % 12 10 28 26 26 23
Distribution of TIMI Flow Rates Prior to PCI After PCI 100 100 % % 60 75 74 60 93 90 17 17 3 4 5 5 6 7 TIMI 3 TIMI 2 TIMI 1 TIMI 0
30-Day Clinical Outcomes % P=.57 P=.66 P=.07 P=.05 15 10 5 0 0.7 1.0 0.3 0.6 All-cause death Cardiac death 2.0 4.6 Myocardial infarction 2.6 5.9 MACE* * No TLR occurred and only 1 pt () died suddenly (probable stent thrombosis) during 30-day follow-up
Primary Endpoint: Death/MI/TLR 50 Cumulative Incidence (%) 40 30 10 P=.03 RR 0.65 [0.45-0.96] 22.1% 15.4% 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months After Randomization
All-cause Death 50 Cumulative Incidence (%) 40 30 10 P=.82 RR 1.09 [0.52-2.25] 5.2% 0 4.7% 0 1 2 3 4 5 6 7 8 9 10 11 12 Months After Randomization
Myocardial Infarction Cumulative Incidence (%) 50 40 30 10 P=.27 RR 0.66 [0.32-1.37] 6.0% 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months After Randomization 4.2%
Death or Myocardial Infarction 50 Cumulative Incidence (%) 40 30 10 P=.27 RR 0.75 [0.45-1.26] 10.9% 8.5% 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months After Randomization
Definite/Probable Stent Thrombosis 5 Cumulative Incidence (%) 4 3 2 1 P=.99 RR 1.01 [0.14-7.18] 0.7% 0.7% 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months After Randomization
Target Lesion Revascularization 50 Cumulative Incidence (%) 40 30 10 P=.02 RR 0.52 [0.30-0.90] 13.1% 0 7.2% 0 1 2 3 4 5 6 7 8 9 10 11 12 Months After Randomization
Target Vessel Revascularization TLR % P=.02 RR 0.52 [0.30-0.90] TVR % P=.03 RR 0.61 [0.39-0.95] 17.8 15 13.1 11.5 10 7.2 10 5 0 0
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.