Last Window for BMS Closes as LEADERS-FREE Supports DES in High-Bleeding-Risk ACS

PARIS, France—For acute coronary syndrome patients prescribed just 1 month of dual antiplatelet therapy, treatment with a polymer-free drug-coated stent results in significantly better clinical outcomes when compared with individuals treated with a bare-metal stent, researchers reported today at EuroPCR.

In the ACS substudy of the LEADERS FREE trial, which included patients at high risk for bleeding, the newer stent (BioFreedom, Biosensors International) showed a significantly lower rate of clinically driven target lesion revascularization when compared with a conventional bare-metal stent (Gazelle, Biosensors International). In addition, treatment with the BioFreedom stent, which is currently approved in Europe but not in the United States, was associated with a significantly lower rate of the combined endpoint of cardiac death, MI, and stent thrombosis. 

For lead investigator Christoph Naber (Contilia Heart- and Vascular Center Essen, Germany), who presented the results during a late-breaking session, the findings are strong enough to alter current treatment patterns in ACS patients at a high risk for bleeding. 

“We believe that current guidelines and clinical practice needs to change,” Naber told the media during a press briefing at EuroPCR. The bottom line is that bare-metal stents no longer cut it in these higher-risk ACS patients. While bare-metal stents are believed to be a good choice in ACS patients unable to take sustained dual antiplatelet therapy, the analysis shows the drug-coated stent, coupled with 1 month of DAPT, is a better option. “Bare-metal stents can no longer be recommended,” he said. “The drug-coated stent currently has the best evidence for this indication.”

Results of the analysis were published simultaneously in the European Heart Journal.

LEADERS FREE Showed Advantage of BioFreedom Stent

LEADERS FREE, which was reported by TCTMD and published in the New England Journal of Medicine in 2015, included 2,466 patients at high risk for bleeding and showed that use of the drug-coated stent resulted in significantly better safety and efficacy compared with the bare-metal stent. As designed, the study included older patients (mean age 76 years) and patients with significantly more comorbidities, including kidney failure, and those in need of major surgery or oral anticoagulation.    

Speaking with the media at EuroPCR, Naber explained that the European Society of Cardiology 2015 guidelines for the management of ACS recommend dual antiplatelet therapy for 3 to 6 months in patients at a high risk of bleeding (recommendation IIa, level of evidence A). The BioFreedom device is a polymer-free and carrier-free stent with umirolimus (also known as biolimus A9) coated directly onto the abluminal metal surface of the device.

“The device allows us to avoid late polymeric effects,” said Naber. “The drug is transferred rapidly into the vessel wall—it has a half-life of about 20 days—and we know from the LEADERS FREE trial that dual antiplatelet therapy can be safely shortened to 1 month.”

At 1 year, treatment with the drug-coated stent in the ACS patients resulted in a 59% reduction in the risk of target lesion revascularization and a 52% reduction in the safety endpoint, a composite of cardiac death, MI, and definite/probable stent thrombosis. The safety endpoint was driven by a statistically significant reduction in the risk of cardiac death and MI. Bleeding rates were “remarkably high” in both arms—close to 10%—but not different between the two stents.

Thomas Cuisset, MD (University Hospital, Marseille, France), who commented on the study during the session, said that since the publication of the main LEADERS FREE trial results there have been questions about whether or not it is safe to scale back dual antiplatelet therapy to 1 month in all ACS patients treated with a drug-eluting stent. The study, he pointed out, was not designed to answer that question as it was a trial of two stents, rather than a trial of different short- and long-term dual antiplatelet therapy. 

“The main conclusion from LEADERS FREE is that a drug-coated stent is better than a bare-metal stent in a specific population requiring 1-month dual antiplatelet therapy,” he said. It did not show that short-term dual antiplatelet therapy is a safe option in all ACS patients treated with drug-coated stents. Dual antiplatelet therapy should be tailored not only to the device, but also to individual patient characteristics, said Cuisset.   

In appraising the data, Cuisset said bare-metal stents are no longer the gold standard as a control arm, even in this group of high-bleeding-risk ACS patients, making the results difficult to interpret in the real world. 

For Naber, the positive results with BioFreedom, which is polymer-free, cannot be extrapolated to other drug-eluting devices. He added that clinical trials have not definitively shown that patients treated with other drug-eluting stents can be treated with just 1 month of dual antiplatelet therapy, and that before a head-to-head comparison is done, this treatment course needs to be shown to be safe with drug-eluting stents.

• Naber CK, Urban P, Ong PJ. Biolimus-A9 polymer-free coated stent in high bleeding risk patients with acute coronary syndrome: a LEADERS FREE ACS substudy. Eur Heart J. 2016; Epub ahead of print.

Disclosures:

• Naber reports owning shares in the European Cardiovascular Research Center (CERC), the clinical research organization overseeing the LEADERS FREE study. 

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