Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug-Coated Stent Versus the Gazelle Bare-Metal Stent in Patients at High Bleeding Risk II - LEADERS FREE II

Sep 22, 2018
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Biosensors Europe SA, Morges, Switzerland
Date Presented:
09/22/2018
Date Published:
09/22/2018
Date Updated:
09/22/2018
Original Posted Date:
09/22/2018
References

Contribution To Literature:

The LEADERS FREE II trial showed that clinical outcomes following biolimus A9 DCS implantation are superior to BMS in patients with high bleeding risk and able to take only 1 month of DAPT.

Description:

This trial sought to compare the safety and efficacy of the biolimus-eluting BioFreedom drug-coated stent (DCS) among elderly patients at high risk for bleeding post-percutaneous coronary intervention (PCI).

Study Design

This was designed as a pivotal trial for Food and Drug Administration (FDA) approval of the BioFreedom stent. This was a single-arm study where 1,203 patients received the biolimus DCS. These were compared with outcomes among patients who received the bare-metal stent (BMS) (n = 1,189) in the LEADERS FREE trial.

  • Total number of enrollees: 1,203
  • Duration of follow-up: 12 months
  • Mean patient age: 75 years
  • Percentage female: 31%

Inclusion criteria:

  • Age ≥75 years
  • Adjunctive oral anticoagulation treatment planned to continue after PCI
  • Baseline hemoglobin ≥11 g/dl (or anemia requiring transfusion during the prior 4 weeks)
  • Any prior intracerebral bleed at any time
  • Any stroke during the past year
  • Hospital admission for bleeding during the prior 12 months
  • Non-skin cancer diagnosed or treated ≤3 years
  • Planned daily nonsteroidal anti-inflammatory drug (other than aspirin) or steroids for ≥30 days after PCI
  • Planned major surgery (within 1 year)
  • Renal failure (calculated creatinine clearance <40 ml/min)
  • Thrombocytopenia (<100,000/mm3)
  • Severe chronic liver disease
  • Expected noncompliance to prolonged dual antiplatelet therapy (DAPT) for other medical (nonfinancial) reasons

Other salient features:

  • Acute coronary syndrome: 44%
  • Mean number of stents per patient: 1.85
  • Total stented length: 34.5 mm vs. 31.6 mm, p = 0.0009
  • DAPT on follow-up: 92.1% at 1 month, 8.7% at 2 months, 8.5% at 6 months

Principal Findings:

The primary safety endpoint of cardiac death or myocardial infarction (MI) at 1 year for DCS vs. BMS was 8.6% vs. 12.3% (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.51-0.88).

The primary efficacy endpoint at 1 year for target lesion revascularization (TLR) was 6.1% vs. 9.3% (HR 0.63, 95% CI 0.45-0.87).

  • Cardiac death: 3.4% vs. 5.1%, p = 0.03
  • MI: 5.9% vs. 8.8%, p = 0.01

Secondary outcomes at 1 year (DCS vs. BMS):

  • Stent thrombosis: 1.9% vs. 2.2%, p = 0.63; acute/subacute: 1.2% vs. 1.2%, late: 0.9% vs. 0.9%
  • Bleeding Academic Research Consortium (BARC) 3-5: 7.0% vs. 7.3%, p = 0.88
  • Any bleeding: 19.7% vs. 19.0%, p = 0.56

Interpretation:

The results of this trial indicate that clinical outcomes following biolimus A9 DCS implantation are superior to BMS in patients with high bleeding risk and able to take only 1 month of DAPT. There was a significant reduction in MI and TLR up to 1 year of follow-up, with similar rates of stent thrombosis.

This is not a true randomized trial, but rather used historical controls from the LEADERS FREE trial to show reproducibility of results. This study also enrolled >50% patients from North America, and was designed for FDA approval of the stent in the United States.

One must point out that the biolimus A9 stent is not a bioabsorbable stent, but rather a DCS  where the drug is directly coated to the abluminal surface of a stainless-steel stent with a solvent (polymer-free). The drug is more lipophilic than contemporary limus agents and is essentially absorbed almost entirely into the vessel wall in 30 days, leaving behind a plain BMS. In keeping with this, stent thrombosis rates were slightly higher at 1 year than typically seen with second-generation everolimus-eluting stents. There does not appear to be a “catch up” phenomenon for TLR and stent thrombosis after 1 year. This is a very interesting study in a novel stent, conducted specifically in patients who are typically excluded from stent trials.

References:

Presented by Dr. Mitchell W. Krukoff at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2018), San Diego, CA, September 22, 2018.

Keywords: TCT18, Transcatheter Cardiovascular Therapeutics, Acute Coronary Syndrome, Anticoagulants, Drug-Eluting Stents, Geriatrics, Hemorrhage, Myocardial Infarction, Myocardial Revascularization, Percutaneous Coronary Intervention, Renal Insufficiency, Stents, Stroke, Thrombocytopenia, Thrombosis


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