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

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.


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


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.


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

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Cardiac Surgery, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Anticoagulation Management and ACS, Aortic Surgery, Interventions and ACS

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

< Back to Listings