Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol- and Zotarolimus-Eluting Stents 5 - ISAR-TEST 5

Description:

A novel dual drug-eluting stent (DES) with rapamycin and probucol had shown promising results in first-in-man studies. The ISAR-TEST 5 trial sought to compare outcomes after dual-DES versus zotarolimus-eluting stent (ZES) implantation in all-comers with coronary artery disease (CAD).

Contribution to the Literature: The ISAR-TEST 5 trial showed that a dual-DES is noninferior to ZES for reducing MACE in patients with CAD.

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 native coronary arteries
  • Informed, written consent
  • Age ≥18 years

    Number of enrollees: 3,002
    Duration of follow-up: 12 months
    Mean patient age: 68 years
    Percentage female: 24
    Ejection fraction: 52.5%

Exclusions:

  • Cardiogenic shock
  • Lesions located at left main stem or bypass graft
  • Malignancies with life expectancy <1 year
  • Allergies to study medication 

Primary Endpoints:

  • Composite of cardiac death, target vessel-related myocardial infarction, TLR at 1-year post-index percutaneous coronary intervention (PCI)

Secondary Endpoints:

  • All-cause death at 1-year post-index PCI
  • Incidence of definite/probable stent thrombosis at 1-year post-index PCI
  • In-segment binary restenosis at follow-up angiography
  • In-stent late luminal loss at follow-up angiography

Drug/Procedures Used:

Patients were randomized to dual-DES or ZES (Endeavor Resolute) in a 2:1 fashion.

Concomitant Medications:

All patients received 600 mg of clopidogrel and 500 mg of aspirin prior to or during the procedure. Clopidogrel was then continued at 75 mg bid until discharge, and then 75 mg daily for a minimum of 6 months. Aspirin at 200 mg daily was continued indefinitely.

Principal Findings:

A total of 3,002 patients were randomized, 2,002 to dual-DES and 1,000 to ZES. Baseline characteristics were fairly similar between the two arms. About 30% had diabetes mellitus, and 30% had a history of myocardial infarction (MI). About 43% of patients presented with an acute coronary syndrome, and multivessel disease was noted in 84% of the patients; multivessel percutaneous coronary intervention (PCI) was undertaken in 37%. The left anterior descending artery was the target vessel in 45% of the patients. The mean reference vessel diameter was 2.8 mm, with a mean lesion length of 16.6 mm.

Thirty-day outcomes, including cardiac death (0.6% vs. 0.7%, p = 0.61) and target lesion revascularization (TLR) (0.6% vs. 0.8%, p = 0.52), were similar between the dual-DES and ZES arms. On angiographic follow-up at 6-8 months, in-stent late lumen loss (0.31 vs. 0.30 mm, p = 0.50) and in-segment binary restenosis (13.3% vs. 13.4%, p = 0.95) were similar between the dual-DES and ZES arms, respectively. The primary endpoint of major adverse cardiac events (MACE) at 1 year was similar between the dual-DES and ZES arms (13.1% vs. 13.5%, p = 0.74). Other clinical outcomes at 12 months including all-cause mortality (3.6% vs. 4.7%, p = 0.13), definite or probable stent thrombosis (1.1% vs. 1.2%, p = 0.80), and TLR (10.3% vs. 10.4%, p = 0.94) were similar between the two arms.

Five-year follow-up: The primary endpoint for dual-DES vs. ZES was 23.8% vs. 24.2% (p = 0.8). TLR: 14.7% vs. 14.7% (p = 0.98); MI: 4.3% vs. 4.8% (p = 0.6); and stent thrombosis: 1.3% vs. 1.6% (p = 0.64).

Interpretation:

The results of the ISAR-TEST 5 trial indicate that a dual-DES is noninferior to ZES for reducing MACE at 12 months in patients with CAD, with equivalent angiographic characteristics at 6-8 months. Long-term results are also similar. These results are interesting, since the dual-DES studied here is polymer-free, and thus, could potentially be used with a shorter duration of dual antiplatelet therapy, as compared with conventional DES. This will need to be explicitly studied in future trials. This trial, however, establishes the clinical safety and efficacy of a dual-DES stent, as compared with a conventional DES.

References:

Kufner S, Sorges J, Mehilli J, et al. Randomized Trial of Polymer-Free Sirolimus- and Probucol-Eluting Stents Versus Durable Polymer Zotarolimus-Eluting Stents: 5-Year Results of the ISAR-TEST-5 Trial. JACC Cardiovasc Interv 2016;9:784-92.

Massberg S, Byrne RA, Kastrati A, et al., on behalf of the Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus- Eluting Stents (ISAR-TEST 5) Investigators. Polymer-Free Sirolimus- and Probucol-Eluting Versus New Generation Zotarolimus-Eluting Stents in Coronary Artery Disease. The Intracoronary Stenting and Angiographic Results: Test Efficacy of Sirolimus- and Probucol-Eluting Versus Zotarolimus-Eluting Stents (ISAR-TEST 5) Trial. Circulation 2011;124:624-32.

Presented by Dr. Julinda Mehilli at the Transcatheter Cardiovascular Therapeutics Meeting (TCT 2010), Washington, DC, September 25, 2010.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Interventions and ACS, Chronic Angina

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Coronary Restenosis, Thrombosis, Drug-Eluting Stents, Polymers, Constriction, Pathologic, Sirolimus, Angioplasty, Balloon, Coronary, Diabetes Mellitus, Probucol


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