Polymer-Free Drug-Coated Stent Benefits Hold Up At 2 Years in High-Bleeding-Risk Patients

Patrice Wendling

October 31, 2016

WASHINGTON, DC — The safety and efficacy benefits of the BioSensors BioFreedom polymer-free drug-coated stent (DCS) persist out to 2 years in patients at high risk for bleeding following PCI and treated with only 30 days of dual antiplatelet therapy (DAPT)[1].

"There was no single subgroup that could be identified for which the use of a bare-metal stent was superior to a DCS," Dr Philip Urban (La Tour Hospital, Geneva, Switzerland) said in presenting the LEADERS FREE trial at a late-breaking clinical-trials session here at TCT 2016.

Two-year follow-up in 98% of the 2466 randomized patients showed that the primary safety end point—a composite of cardiac death, MI, or stent thrombosis—occurred in 12.6% of patients treated with the BioFreedom DCS and 15.3% treated with the BioSensors Gazelle bare-metal stent (hazard ratio [HR] 0.80, P=0.039).

This was likely driven by the increased need for repeat revascularization in the bare-metal–stent arm, with 12% of bare-metal–stent and 6.8% of DCS patients undergoing the primary efficacy end point of target lesion revascularization (HR 0.54, P<0.0001), he said.

Rates of very late stent thrombosis were low, at 0.1% in both arms of the study, led by Dr Philippe Garot (Cardiovascular Institute Paris Sud, Quincy, France) and simultaneously published online in the Journal of the American College of Cardiology.

Device-Specific Benefits?

Dr Philip M Urban

Urban observed that high-bleeding-risk patients represent about 20% of cath-lab volume and are poor candidates for guideline-mandated DAPT durations. Current guidelines recommend using either a bare-metal stent and 1-month DAPT or a contemporary DES with "shortened" DAPT.

Advantages of the BioFreedom device are the lack of side effects with no polymer and 98% transfer of the biolimus A9 (a highly lipophilic sirolimus analog) coating into the vessel wall within 30 days, "and that kinetic is a good fit we think for short DAPT," he said.

Overall, only 7.6% of bare-metal–stent and 5.3% of DCS patients were still on DAPT at 2 years (P=0.03), while three-fourths of patients were on single antiplatelet therapy, about 15% were taking no antiplatelet drug, and one-third were on oral anticoagulants.

When asked during the panel discussion whether the favorable DCS outcomes are device-specific or translatable to other polymer-free devices, Urban replied, "Your guess is as good as mine." He added that there are at least four trials under way evaluating <3 months DAPT with slower-eluting stents but that the only available data concerning a rapid-elution device and very short DAPT come from Medtronic's Endeavor zotarolimus-eluting stent, which also seemed to work better than bare-metal stents in the ZEUS trial but had a polymer.

Panelist Dr Dariusz Dudek (Institute of Cardiology, Krakow, Poland) followed up, asking, "Is it justified to use bare-metal stents any longer because we see that the new-generation drug-eluting stents could be better?"

Urban pointed out that the BioFreedom stent, approved in Europe in January 2013, is not yet available in the US, "so in this case there must be some cases for whom a bare-metal stent remains a reasonable option." That said, he hasn't done a bare-metal–stent case in the past year, and his hospital no longer keeps them on the shelf; "For me, bare-metal stents have become unnecessary."

At a press briefing, discussant Dr Dean Kereiakes (Christ Hospital Heart and Vascular Center, Cincinnati, OH) quipped that there's no reason to use a bare-metal stent "unless you're cultivating business." He said there are "outdated US guidelines that have perpetrated the use of bare-metal stents" and looking at ZEUS, LEADERS FREE ACS, and the LEADERS FREE whole trial, "the theme is overwhelming: bare-metal stents have increased stent-thrombosis rates."

Press-briefing moderator Dr Ajay Kirtane (New York-Presbyterian Hospital/Columbia University Medical Center, New York City) countered that with the BioFreedom device not available here, "in the US population, it's a little bit irresponsible right now to say that there's no reason or role for bare-metal stents."

Commenting to heartwire from Medscape, Kirtane said the guidelines have changed to a minimum 3 months of DAPT for high-bleeding-risk patients with a DES, "so the number of people who fall into that window are fewer, but there is still a role for [bare-metal stents for] some of these folks. I have a patient in the hospital right now who requires a surgery whom we had this very discussion about, and I think as a clinician it's good to have other options on the table than drug-eluting stents."

Persistent Bleeding, Thrombotic Events

Urban stressed that the balance of thrombosis and bleeding is particularly important in this poorly studied patient group and that "these patients suffer from a persistently high incidence of major bleeding and coronary thrombotic events."

At 2 years, the significant difference favoring the DCS over the bare-metal stent remained for coronary thrombotic events (8.2% vs 10.6%, P=0.045) but was not present for major bleeding (8.9% vs 9.2%, P=0.95).

Both events occurred at roughly the same rate and drove 1-year mortality up to 27%, compared with just 6% among patients with neither adverse event.

In multivariate analysis, correlates associated with the primary safety end point were congestive heart failure, multivessel disease, the number of implanted stents, and use of a bare-metal stent. For major bleeding, predictors were planned oral anticoagulants and serum creatinine >150 µmol/L.

To make matters more complex, age >75 years and anemia predicted both outcomes, "stressing the difficulty there is in trying to tease out strategies to address one or the other of these two problems in this patient group," Urban told the media.

"Identification of predictors of both the composite primary safety event and major bleeding may help design future trials of DAPT duration of high-bleeding-risk patients," he concluded.

The study was sponsored by Biosensors Europe. Urban reported consulting for Biosensors. Garot reported no relevant financial relationships. Disclosures for the coauthors are listed in the paper. Dudek reported having no relevant financial relationships. Kereiakes reported that within the past year he or his spouse had received consultant fees or honoraria from or served on the speakers' bureau for Harvard Clinical Research Institute, Boston Scientific, Abbott Vascular, Micell Technologies, Sino Medical Sciences Technology, Caliber Therapeutics, and Svelte Medical Systems and had equity in Ablative Solutions. Kirtane reported that within the past year he or his spouse had received grant support or a research contract with Medtronic, Boston Scientific, Vascular Dynamics, St Jude Medical, Abiomed, Abbott Vascular, and Eli Lilly.

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org, follow us on Twitter and Facebook.

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