Is Drug-Eluting Stenting Associated With Improved Results in Coronary Artery Bypass Grafts? - ISAR-CABG

Contribution To Literature:

The ISAR-CABG trial showed that first-generation DES do not have better clinical outcomes compared with BMS over 5 years of follow-up.

Description:

Although drug-eluting stents (DES) have been shown to be superior to bare-metal stents (BMS) in reducing in-stent restenosis and target lesion revascularization (TLR) in native coronary arteries, data comparing their performance in saphenous vein grafts are limited. The current trial sought to compare outcomes between DES and BMS in saphenous vein graft (SVG) lesions.

Study Design

  • Blinded
  • Parallel
  • Randomized

Patient Populations:

  • Patients with ischemic symptoms or evidence of myocardial ischemia in the presence of ≥50% de novo stenosis located in SVGs

    Number of enrollees: 610
    Duration of follow-up: 1 year; 5 years
    Mean patient age: 73 years
    Percentage female: 15%
    Ejection fraction: 49.3%

Exclusions:

  • Cardiogenic shock
  • Target lesion located in arterial grafts
  • Malignancies with life expectancy <1 year
  • Allergies to study medication

Primary Endpoints:

  • Composite of death, MI, and ischemia-driven TLR at 1 year

Secondary Endpoints:

  • All-cause mortality
  • MI
  • Ischemia-related TLR
  • Incidence of definite/probable stent thrombosis at 1 year post-index PCI

Drug/Procedures Used:

Patients with de novo SVG lesions were randomized to receive either DES (sirolimus-eluting stents or paclitaxel-eluting stents) or BMS (the most frequent being MULTILINK Vision, Driver, and the Yukon stents, all with a strut thickness <100 microns).

Concomitant Medications:

All patients received 500 mg of aspirin and 600 mg clopidogrel. In addition, all patients received 75 mg twice daily till discharge, followed by 75 mg daily for a minimum of 6 months. Aspirin 200 mg daily was continued indefinitely.

Principal Findings:

A total of 610 patients were randomized, of which 303 received DES and 307 BMS. Baseline characteristics were fairly similar between the two arms. About 36% had diabetes, 56% had prior myocardial infarction (MI), and the mean SVG age was 13.5 years. Most patients presented with stable angina (61%), and 15% presented with acute MI.

Multilesion PCI was performed in 23% of the patients, and 4% had more than one SVG intervention. The mean vessel diameter was 3.37 mm, and the total stented length was about 27 mm. About 17% of patients had aorto-ostial disease, 25% had proximal SVG disease, 27% had medial disease, and 16% had distal disease. About 5% of patients had TIMI 0 flow at the start of the procedure. Embolic protection devices were not utilized in any of the patients.

Major adverse cardiac events (MACE) at 30 days was lower in DES compared with BMS (2.6% vs. 5.9%, p = 0.05), but not all-cause mortality (0.7% vs. 1.0%, p = 0.57) or MI (2.0% vs. 4.6%, p = 0.07). MACE at 1 year, the primary endpoint, was significantly lower in the DES arm compared with BMS (15.0% vs. 22.1%, relative risk 0.64, 95% confidence interval 0.44-0.94, p = 0.02), driven predominantly by a reduction in ischemia-driven target lesion revascularization (TLR) (6.8% vs. 13.1%, p = 0.01). No difference was noted in death (5.1% vs. 4.7%, p = 0.83), MI (4.2% vs. 6.0%, p = 0.27), or stent thrombosis (0.7% vs. 0.7%, p = 0.99). 

5-year follow-up: MACE for DES vs. BMS: 55.5% vs. 53.6% (p = 0.89). Death/MI: 32.8% vs. 36.6% (p = 0.24), TLR: 33.1% vs. 25.5% (p = 0.27), definite stent thrombosis (2.0% vs. 0.4%, p = 0.14). For both MACE and TLR, there was a significant time interaction (p < 0.01), such that MACE (HR 1.24, 95% CI 0.94-1.63) and TLR (HR 2.02, 95% CI 1.32-3.08) were lower with DES up to 1 year, and then higher than BMS between years 1 and 5.

Interpretation:

The results of the ISAR-CABG trial indicated that DES (first-generation stents, PES and SES) were superior to BMS in reducing MACE at 1 year, mainly due to a reduction in ischemia-driven TLR, but not death, MI, or stent thrombosis. These results are similar to those noted by the SOS trial, and parallel those noted in native coronary vessels.

On longer-term follow-up at 5 years, the benefit with DES over BMS was lost due to higher TLR rates with DES between years 1 and 5. It is unclear if second-generation DES, particularly everolimus-eluting stents, would have a similar higher risk compared with BMS during this time period. They are superior for TLR compared with first-generation DES, but there are limited data for SVG-PCI, where the biology of stent failure may be different compared with native vessels.

References:

Colleran R, Kufner S, Mehilli J, et al., on behalf of the ISAR-CABG Investigators. Efficacy Over Time With Drug-Eluting Stents in Saphenous Vein Graft Lesions. J Am Coll Cardiol 2018;71:1973-82.

Editorial Comment: Brilakis ES, Banerjee S, Burke MN. A New Treatment Strategy for Saphenous Vein Graft Lesions? Letting it Go. J Am Coll Cardiol 2018;71:1983-5.

Mehilli J, Pache J, Abdel-Wahab M, et al. Drug-eluting versus bare-metal stents in saphenous vein graft lesions (ISAR-CABG): a randomised controlled superiority trial. Lancet 2011;378:1071-8.

Presented by Dr. Julinda Mehilli at the ACC.11/i2 Summit, New Orleans, LA, April 4, 2011.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Aortic Surgery, Cardiac Surgery and SIHD, Chronic Angina

Keywords: Risk, Myocardial Infarction, Angina, Stable, Coronary Restenosis, Drug-Eluting Stents, Sirolimus, Constriction, Pathologic, Stents, Paclitaxel, Embolic Protection Devices, Thrombosis, Saphenous Vein, Diabetes Mellitus, Myocardial Revascularization, Percutaneous Coronary Intervention


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