Limus Eluted From A Durable versus ERodable Stent coating - LEADERS

Nov 08, 2011
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Biosensors Europe SA, Switzerland
Date Updated:
11/08/2011
Original Posted Date:
11/08/2011
References

Description:

The goal of the trial was to evaluate treatment with the biolimus-eluting stent from a biodegradable polymer compared with the sirolimus-eluting stent from a durable polymer in patients with stable coronary artery disease or acute coronary syndromes.

Hypothesis:

The biolimus-eluting stent will be non-inferior to the sirolimus-eluting stent.

Study Design

Patients Enrolled: 1,707
Mean Follow Up: 4 years
Mean Patient Age: 65 years
Female: 25%
Mean Ejection Fraction: 56%

Patient Populations:

  • Patients at least 18 years of age with stable coronary artery disease or acute coronary syndromes, including ST-elevation myocardial infarction
  • Reference vessel diameter of 2.25-3.5 mm

Exclusions:

  • Known allergy to any of the study medications or devices
  • Surgery within 6 months that would necessitate the termination of dual antiplatelet therapy
  • Pregnancy
  • Participation in another investigational study
  • Inability to provide informed consent

Primary Endpoints:

Composite of cardiovascular death, myocardial infarction, or urgent target vessel revascularization within 9 months

Secondary Endpoints:

  • Individual components of the composite primary outcome
  • Stent thrombosis
  • Device success
  • In-stent and in-segment percent diameter stenosis
  • Minimal lumen diameter
  • Late lumen loss
  • Binary restenosis

Drug/Procedures Used:

Patients with stable coronary disease or acute coronary syndromes were randomized to the biolimus-eluting stent with a biodegradable polymer (n = 857) or the sirolimus-eluting stent with a durable polymer (n = 850).

Concomitant Medications:

Patients received aspirin indefinitely, clopidogrel (300-600 mg loading dose) for 12 months, intraprocedural unfractionated heparin, and glycoprotein IIb/IIIa inhibitors according to operator discretion.

Principal Findings:

At baseline, there were 24% diabetics, 23% with multi-vessel disease, and 29% with long lesions (i.e., >20 mm). The indication for catheterization was stable angina in 45%, non-ST-elevation acute coronary syndromes in 39%, and ST-elevation myocardial infarction in 16%. Off-label use was 80%. The number of stents used per patient was 1.3 and the total stent length per lesion was 25 mm in both groups. Implantation of study stent was achieved in 97.5% of the biolimus group and 95.7% of the sirolimus group (p = 0.05). Angiographic follow-up was performed in 79% of participants.

At 9 months, the primary outcome of death, myocardial infarction, or urgent revascularization occurred in 9.2% of the biolimus group versus 10.5% of the sirolimus group (p for non-inferiority = 0.003, p for superiority = 0.39). Individual components of the composite outcome were similar at 9 months: cardiovascular mortality (1.6% vs. 2.5%, p for superiority = 0.22), myocardial infarction (5.7% vs. 4.6%, p = 0.30), and urgent target vessel revascularization (4.4% vs. 5.5%, p = 0.29). Cumulative stent thrombosis to 9 months was similar (1.9% vs. 2.0%, p = 0.84), as was stent thrombosis from 30 days to 9 months (0.2% vs. 0.5%, p = 0.41).

In-stent percent diameter stenosis was 20.9% in the biolimus group versus 23.3% in the sirolimus group (p for non-inferiority = 0.001, p for superiority = 0.26). In-stent late loss was 0.13 mm in the biolimus group and 0.19 mm in the sirolimus group.

At 4 years, the primary outcome occurred in 19% of the biolimus group versus 23% of the sirolimus group (p = 0.05). Death: 9% versus 10% (p = 0.76), cardiac death: 6% versus 7% (p = 0.51), Q-wave myocardial infarction: 1% versus 2% (p = 0.17), non-Q-wave myocardial infarction: 8% versus 7% (p = 0.98), and any target lesion revascularization: 10% versus 13% (p = 0.07), respectively. Very late definite stent thrombosis (>1 to 4 years): <1% versus 2% (p = 0.004), respectively.

Interpretation:

Among patients with stable angina and acute coronary syndromes, the use of the biolimus-eluting stent with a biodegradable polymer was non-inferior to the sirolimus-eluting stent with a durable polymer. Specifically, the biolimus stent was non-inferior with regard to death, myocardial infarction, or urgent target vessel revascularization at 9 months. This stent also showed a similar incidence of definite stent thrombosis and was also non-inferior for in-stent percent diameter stenosis.

By 4 years, adverse events appeared to be reduced among the biolimus stent group, largely due to a reduction in very late stent thrombosis.

Strengths of this trial include liberal enrollment, with approximately 80% of procedures performed for off-label indications including ST-elevation myocardial infarction. This trial also utilized a primary clinical composite outcome rather than a surrogate composite outcome.

Biolimus is a semi-synthetic analog of sirolimus with enhanced lipophilicity that is coupled to a polylactic acid biodegradable polymer. In-vivo studies suggest that this polymer is fully converted to lactic acid within 6 to 9 months, leaving the stainless steel stent. Attractive features of this stent include better deliverability and a biodegradable polymer, which may have attenuated late stent thrombosis. Very late stent thrombosis has been a residual problem with first-generation drug-eluting stents. The biolimus-eluting stent with a biodegradable polymer appears to have significantly reduced this complication. This novel device will need to be compared against the everolimus-eluting stent, which also has a very low frequency of stent thrombosis.

References:

Stefanini GG, Kalesan B, Serruys PW, et al. Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial. Lancet 2011;Nov 8:[Epub ahead of print].

Windecker S, Serruys PW, Wandel S, al. Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial. Lancet 2008;372:1163-73.

LEADERS: Limus Eluted From A Durable vs ERodable Stent coating (Randomized comparison of a biolimus-A9 eluting stent with a sirolimus-eluting stent for percutaneous coronary intervention). Presented by Dr. Stephan Windecker at the European Society of Cardiology Congress, Munich, Germany, August/September 2008.

Keywords: Myocardial Infarction, Follow-Up Studies, Angina, Stable, Drug-Eluting Stents, Off-Label Use, Immunosuppressive Agents, Constriction, Pathologic, Sirolimus, Angioplasty, Balloon, Coronary, Polymers, Catheterization, Lactic Acid, Diabetes Mellitus


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