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

Oct 30, 2016
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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:
10/30/2016
Date Published:
10/30/2016
Date Updated:
10/30/2016
Original Posted Date:
10/14/2015
References

Contribution To Literature:

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

Description:

This trial sought to compare the safety and efficacy of the biolimus-eluting BioFreedom drug-coated stent (DCS) with the Gazelle bare-metal stent (BMS) in patients at high risk for bleeding post–percutaneous coronary intervention (PCI).

Study Design

Patients were randomized to either Biofreedom DCS (n = 1,221) or Gazelle BMS (n = 1,211).

  • Total number of enrollees: 2,432
  • Duration of follow-up: 2 years
  • Mean patient age: 75.7 years
  • Percentage female: 30%

Other salient features:

  • Non−ST-segment elevation myocardial infarction (NSTEMI)/STEMI: 26%
  • Multivessel disease: 63%
  • Number of stents per patient: 1.6
  • Mean stent diameter: 3 mm
  • Need for triple therapy at discharge: 33%; only 9.5% were on DAPT beyond 30 days; the rest were on single APT; 33% were also an an anticoagulant

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 DAPT for other medical (nonfinancial) reasons

Principal Findings:

  • Primary safety endpoint: Cardiac death, MI, stent thrombosis at 1 year for DCS vs. BMS: 9.4% vs. 12.9%, p for noninferiority < 0.001; p for superiority = 0.005
  • Primary efficacy endpoint at 1 year: target-lesion revascularization (TLR): 5.1% vs. 9.8%, p < 0.0001
  • Cardiac death: 4.2% vs. 5.3%, p = 0.19
  • MI: 6.1% vs. 8.9%, p = 0.01
  • Stent thrombosis: 2.0% vs. 2.2%, p = 0.7

Secondary outcomes at 1 year for DCS vs. BMS:

  • All-cause mortality: 8% vs. 9%, p > 0.05
  • Bleeding (BARC 1-5): 18.1% vs. 19.1%, p = 0.55
  • Significant bleeding (BARC 3-5): 7.2% vs. 7.3%, p = 0.96

Outcomes at 2 years for DCS vs. BMS:

  • Cardiac death, MI, stent thrombosis for DCS vs. BMS: 12.9% vs. 15.3%, p = 0.039
  • TLR: 6.8% vs. 12.0%, p < 0.001
  • MI: 7.4% vs. 10.1%, p = 0.04
  • Stent thrombosis: 2.1% vs. 2.3%, p = 0.76
  • BARC 3-5 bleeding: 8.9% vs. 9.2%, p = 0.95

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 2 years of follow-up, with similar rates of stent thrombosis. A higher benefit was noted in patients presenting with acute coronary syndrome, no renal failure on admission, lower CRUSADE risk scores, and in those not anemic/requiring transfusion during admission.

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 higher at 1 year than typically seen with second-generation everolimus-eluting stents. There did 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 that are typically excluded from stent trials. If further validated, this stent could be of great clinical utility.

References:

Garot P, Morice MC, Tresukosol D, et al., on behalf of the LEADERS FREE Investigators. Two-Year Outcomes of High Bleeding Risk Patients After Polymer-Free Drug-Coated Stents. J Am Coll Cardiol 2016;Oct 30:[Epub ahead of print].

Presented by Dr. Philip Urban at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2016), Washington, DC, October 30, 2016.

Urban P, Meredith IT, Abizaid A, et al., on behalf of the LEADERS FREE Investigators. Polymer-Free Drug-Coated Stents in Patients at High Bleeding Risk. N Engl J Med 2015;373:2038-47.

Presented by Dr. Philip M. Urban at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2015), San Francisco, CA, October 14, 2015.

Keywords: Acute Coronary Syndrome, Drug-Eluting Stents, Myocardial Infarction, Percutaneous Coronary Intervention, Renal Insufficiency, Stents, Stroke, Thrombocytopenia, Thrombosis, Transcatheter Cardiovascular Therapeutics, Stainless Steel


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