A novel drug-coated stent halved the need for repeat revascularization and had a superior safety profile, compared with a bare-metal stent, in patients with a high risk of bleeding in the LEADERS FREE trial.

The results could mean that these typically older, sicker patients in whom dual antiplatelet therapy is contraindicated because of hemorrhage risk now have a wider range of revascularization options, said lead investigator Dr. Philip Urban.

“Patients who have a high risk of bleeding during percutaneous coronary intervention (PCI) are often excluded from stent and drug trials but constitute a rapidly growing proportion of PCI candidates, and they suffer high event rates,” said Dr. Urban, director of interventional cardiology at La Tour Hospital in Geneva. As the life expectancy increases, the implications are profound because roughly one-fifth of all PCI patients globally could be candidates for this type of treatment.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, which was sponsored by the Cardiovascular Research Foundation. The results also were published online (N Engl J Med. 2015 Oct 14. doi: 10.1056/NEJMoa1503943).

“I hope these results will change practice as early as next week in Europe and elsewhere,” he said. The device is currently CE marked in Europe and is available in some parts of Asia. A clinical trial for the device is currently in the preliminary stages in the United States.

The current standard for PCI in patients at high risk for hemorrhage is to use bare-metal, instead of drug-eluting, stents. Although this protocol lowers the potential risk for bleeding and other complications often caused by extended dual antiplatelet therapy (DAPT), it exposes these patients to a higher risk of restenosis.

Rather than use a drug delivery polymer, the Biolimus A9-coated BioFreedom (Biosensors International) is polymer free and uses a stainless steel stent microstructured to hold a proprietary lipophilic drug on its outer surface. The drug is absorbed by the body within a month of placement.

The first of its kind, the double-blinded LEADERS FREE trial randomly assigned 2,466 PCI patients at high risk for bleeding to receive either the test stent or the standard platform Gazelle bare-metal stent. The procedures were performed at nearly 70 participating sites around the world, excluding the United States. More than half of all patients were accessed transradially, which was preferable to transfemoral access, according to Dr. Urban, because of the lower associated bleeding rates.

All patients were given 1 month of antiplatelet therapy after their intervention: about two-thirds of each group received DAPT and one-third received triple antiplatelet therapy. All were then switched to aspirin alone for 1 year.

At 390 days, there was nearly a 50% reduction in the need for repeat revascularization in the 1,221 patients receiving the drug-coated stent (5.1%), compared with 1,221 receiving the bare-metal stent (9.8%), with the difference reaching statistical significance for superiority for this primary efficacy endpoint (P < .001 for superiority).

Patients in the study arm also had a 29% reduction in risk of cardiac death, myocardial infarction, or stent thrombosis, the primary safety endpoint. At 390 days, these events occurred in 9.4% of the drug coated–stent patients, compared with 12.9% of the controls, a statistically significant difference for both noninferiority (P < .0001) and superiority (P = .005).

The study was done in patients typically excluded from such a trial, although, according to Dr. Urban, the PCI procedures performed were no more complex than usual. More than half the patients, three-quarters of whom were men in their mid- to late-70s, also had a range of comorbidities such as diabetes, kidney disease, and atrial fibrillation. Patients taking anticoagulants, those who had experienced a stroke within the past year, those expected to have major surgery within the year, and those who had undergone cancer treatment within the past 3 years also were included.

Bleeding events in the year following did not differ significantly between groups: 18.1% in the study group and 19.1% of controls had BARC 1-5 bleeding; 13.9% in the test arm and 14.7% of controls had BARC 2-5 events; and 7.2% in the study group and 7.3% of controls experienced BARC 3-5 events.

In the past, Dr. Urban had theorized that the trial would help to quantify not only risk for hemorrhage, but also the thrombotic risk in this patient population. In an interview, Dr. Urban said that, while the stent thrombosis rate was nearly identical in both groups in the trial, “the safety advantage of the drug-coated stent was especially apparent in the more thrombotic milieu.”

LEADERS FREE was underwritten by Biosensors International, maker of the BioFreedom stent. Dr. Urban and several of his coinvestigators disclosed relationships with device makers, including Edward Lifesciences, Terumo, Abbott Vascular, and Quest Medical.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

TCT: Novel drug-coated stent bests bare-metal in patients at high bleeding risk