International Randomized Comparison Between DES Limus Carbostent and Taxus Drug-Eluting Stents in the Treatment of De Novo Coronary Lesions - NEXT

Description:

It is currently believed that the polymer coating in currently available drug-eluting stents (DES) predisposes to an increased risk of stent thrombosis. This has evoked interest in the incorporation of biodegradable polymers and polymer-free stent platforms in the next generation of DES. The current trial sought to compare intermediate outcomes with the use of a polymer-free DES compared with paclitaxel-eluting stents (PES) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI).

Hypothesis:

Polymer-free DES (Cre8) would be noninferior to permanent polymer-based PES stents in reducing late lumen loss at 6 months.

Study Design

  • Blinded
  • Parallel
  • Placebo Controlled
  • Randomized

Patient Populations:

  • Patients with either stable angina, unstable angina, or documented silent ischemia
  • Single de novo lesion ≤20 mm length
  • Maximum two different epicardial arteries
  • Diameter between 3 mm and 3.75 mm

    Number of enrollees: 323
    Duration of follow-up: 1 year
    Mean patient age: 64.7 years
    Percentage female: 28%

Exclusions:

  • Clinical:
  • PCI within 30 days
  • Acute myocardial infarction within 72 hours
  • Renal failure
  • Left ventricular ejection fraction ≤30%
  • Other significant comorbidities

  • Angiographic:
  • Left main disease
  • Bifurcation and ostial lesions
  • Chronic total occlusions
  • Presence of severe calcification
  • Excessive tortuosity

Primary Endpoints:

  • In-stent angiographic LLL at 6 months

Secondary Endpoints:

  • Clinical events at 12 months

Drug/Procedures Used:

Patients were randomized in a 1:1 fashion to either the Cre8 stent or the PES (Taxus Liberté). Cre8 is a polymer-free stent with a thin (80 µm) cobalt-chromium alloy L605, integrally coated by an ultra-thin (0.3 µm) passive carbon coating (i-Carbofilm, CID, Saluggia, Italy). The amphilimus formulation, constituted by sirolimus (0.9 µg/mm2) formulated with an excipient composed of a long-chain fatty acid mixture, to modulate the drug release, is loaded into abluminal reservoirs to obtain a targeted elution toward the vessel wall. Predilation was mandatory in all lesions. Two stent sizes were available—3.0 and 3.5 mm; lengths ranged from 12-25 mm.

Concomitant Medications:

Dual antiplatelet therapy (DAPT) for a minimum of 6 months; aspirin recommended indefinitely

Principal Findings:

A total of 323 patients were enrolled, 162 to Cre8 and 161 to PES. Baseline characteristics were fairly similar between the two arms. About 27% had diabetes mellitus, 15% had undergone prior PCI, and 24% were current smokers. The left anterior descending artery was the target vessel in about 46% of the patients. The mean lesion length was about 15 mm, with a mean reference vessel diameter of about 2.78 mm, and a mean % stenosis of 65%.

The primary outcome of in-stent late lesion loss (LLL) at 6 months was significantly lower in the Cre8 arm, as compared with the PES arm (0.14 mm vs. 0.34 mm, p < 0.0001 for noninferiority, p < 0.0001 for superiority). The incidence of in-stent restenosis (≥50%) was similar at 6 months (3.1% vs. 2.0%, p = 0.72). Similar results were noted in diabetic patients. Intravascular ultrasound measurements were conducted in about 20% of patients at 6 months; neointimal hyperplasia volume was lower in the Cre8 arm.

All clinical endpoints at 12 months were similar, including major adverse cardiac events (6.1% vs. 6.8%, p = 0.81), all-cause mortality (1.4% vs. 2.0%, p = 1.0), myocardial infarction (0.7% vs. 1.4%, p = 1.0), target lesion diameter (4.7% vs. 6.1%, p = 0.61), and stent thrombosis (0.6% vs. 0.6%, p = 1.0).

Interpretation:

The results of this trial indicate that a polymer-free amphilimus-eluting stent, Cre8, is superior to a permanent polymer-based PES, Taxus Liberté, at reducing LLL at 6 months; clinical outcomes at 12 months were similar. The LLL observed in this trial is similar to that noted for sirolimus-eluting stents in earlier trials (indeed, amphilimus is sirolimus-based).

Although these early results with a polymer-free stent are encouraging, future trials will need to compare the Cre8 stent to more contemporary stents such as Xience V (everolimus-eluting stent), which have been shown to be superior to PES for angiographic and clinical outcomes. Its utility in more complex lesions will also need to be assessed. Moreover, the argument that polymer-free stents can be utilized with shorter durations of DAPT (bench testing indicates that the Cre8 stent is essentially a bare-metal stent after 3 months) will need to be explicitly tested.

References:

Carrié D, Berland J, Verheye S, et al. A multicenter randomized trial comparing amphilimus- with paclitaxel-eluting stents in de novo native coronary artery lesions. J Am Coll Cardiol 2012;Jan 25:[Epub ahead of print].

Clinical Topics: Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Lipid Metabolism, Interventions and Coronary Artery Disease, Chronic Angina

Keywords: Coronary Artery Disease, Myocardial Infarction, Follow-Up Studies, Angina, Stable, Drug-Eluting Stents, Fatty Acids, Immunosuppressive Agents, Constriction, Pathologic, Sirolimus, Hyperplasia, Excipients, Chromium Alloys, Percutaneous Coronary Intervention, Stents, Paclitaxel, Polymers, Thrombosis, Diabetes Mellitus


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