Two-Year LEADERS FREE Data Presented for BioSensors' BioFreedom Drug-Coated Stent

October 30, 2016—The 2-year results from LEADERS FREE were reported at TCT 2016, the 28th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in Washington, DC, and simultaneously published online by Philippe Garot, MD, et al in the Journal of the American College of Cardiology.

The randomized LEADER FREE clinical trial, which is dedicated to high bleeding risk patients treated with 1 month of dual-antiplatelet therapy (DAPT), found that the polymer-free BioFreedom drug-coated stent (DCS; Biosensors International Group, Ltd.) remained both significantly safer and more effective than the comparator bare-metal stent (BMS) used in the trial. The 1-year LEADERS FREE results, which were presented at the TCT 2015 meeting, demonstrated superior safety and efficacy of DCS at 1 year.

The TCT press release stated that the background of the study is that patients with a high bleeding risk comprise approximately 20% of patients treated by PCI, but they are usually excluded from trials of devices and antithrombotic drug regimen. Current recommendations for high-risk patients are 1 month of DAPT after BMS implantation and a “shortened” DAPT regimen after DES (usually a minimum of 3–6 months). 

LEADERS FREE examined the use of 1 month of DAPT for both the biolimus A9-eluting BioFreedom DCS and the BMS. The BioFreedom device releases biolimus A9 into the vessel wall over a period of 4 weeks without the use of a polymer to aid drug delivery.

As summarized by TCT, the prospective double-blind randomized study enrolled 2,466 patients with high bleeding risk during PCI. At 68 centers in Europe, Asia, and Canada, patients were randomized 1:1 to receive either a DCS (n = 1,221) or a BMS (n = 1,211). The primary safety endpoint was a composite of cardiac death, myocardial infarction (MI), or stent thrombosis. The primary efficacy endpoint was clinically driven target-lesion revascularization (CD-TLR). 

The LEADERS FREE investigators found that 97.7% (1,193) of surviving DCS patients and 98.3% (1,191) of surviving BMS patients had follow-up data available for analysis at 2 years. The primary safety endpoint at 2 years was 12.6% for DCS compared to 15.3% for BMS (hazard ratio [HR], 0.8; 95% confidence interval [CI], 0.64–0.99; P = .039). The results for the primary efficacy endpoint of CD-TLR at 2 years were 6.8% for DCS versus 12% for BMS (HR, 0.54; 95% CI, 0.41–0.72; P < .0001).

Major bleeding occurred in 8.9% DCS and 9.2% BMS patients (P = .95), and a coronary thrombotic event (MI and/or stent trombosis) in 8.2% of DCS and 10.6% of BMS patients (P = .045). 

Confirming the relative importance of both thrombotic and bleeding events, subsequent mortality was 27.1% at 1 year after a major bleed, and 26.3% at 1 year after a thrombotic event, noted the investigators.

In the TCT announcement, LEADERS FREE lead investigator Philip M. Urban commented, “The 2-year results from the LEADERS FREE trial clearly show that the use of a polymer-free biolimus A-9–coated stent was both significantly safer and more effective than a BMS for patients at high risk of bleeding treated with a 1-month course of DAPT.” 

Dr. Urban, who is Director of Invasive Cardiology at La Tour Hospital in Geneva, Switzerland, continued, “These patients suffer from a persistently high incidence of bleeding and coronary thrombotic events, both of which are associated with a high and similar mortality over a one-year period. Therefore, identification of predictors of both the composite primary safety event and major bleeding may help design future trials of DAPT duration for this population.”