This article is more than 5 years old. Information may no longer be current.
LEADERS FREE II: Superior safety, efficacy in drug-coated stent vs. BMS with 30 days of DAPT
SAN DIEGO — A drug-coated stent had superior safety and efficacy regarding death, MI and target lesion revascularization at 1 year compared with a bare-metal stent, according to data presented at TCT 2018.
The drug-coated stent (BioFreedom, Biosensors International) assessed in this trial was part of the pivotal trial to support the device registration decision in the United States, Mitchell W. Krucoff, MD, professor of medicine at Duke University School of Medicine and member in the Duke Clinical Research Institute, said during the press conference.
“This stent is commercially available in the European theater, but currently is not available for patients in North America,” Krucoff said during the press conference.
Objectives of the LEADERS FREE II trial were to reproduce and generalize the findings from the LEADERS FREE trial in a single-arm design.
As Cardiology Today’s Intervention previously reported, the LEADERS FREE trial found that the polymer-free drug-coated stent maintained better safety and efficacy compared with bare-metal stents at 2 years in patients at high risk for bleeding.
For the LEADERS FREE II study, a unique cohort of 1,148 patients with high bleeding risk was enrolled and compared in a propensity-matched analysis to the bare-metal controls arm (n = 1,189) from the LEADERS FREE trial. The primary safety and efficacy endpoints were the same as the original trial, which was a composite of cardiac death and MI at 1 year and clinically driven target lesion revascularization at 1 year, respectively.
Patients enrolled in the trial had a mean high bleeding risk criteria of 1.74 per patient.
The primary safety endpoint occurred in 12.3% of patients assigned the BMS vs. 8.6% assigned the drug-coated stent (risk difference = –3.7%; 95% CI, –6.6 to 1.4; HR = 0.67; 95% CI, 0.51-0.88; P for noninferiority < .0001; P for superiority = .0025).
Both components of the primary safety endpoint were statistically significant in favor of the drug-coated stent, Krucoff said at the press conference.
There was no significant difference in the secondary safety endpoints of all-cause death (P = .21), definite and probable stent thrombosis (P = .63), acute and subacute stent thrombosis (P = .87) and late stent thrombosis (P = .75).
“There was no sign of any safety concern for the DCS platform with 30 days of DAPT,” Krucoff said.
The primary efficacy endpoint occurred in 9.3% of patients assigned BMS in the control group and 6.1% in patients assigned drug-coated stents (difference = –3.2%; 95% CI, -5.5 to –0.7; HR = 0.63; 95% CI, 0.45-0.87; P for superiority = .0111).
The secondary efficacy endpoints of urgent target lesion revascularization (P = .022), target vessel revascularization (P = .006) and any revascularization (P = .014) were all consistent with the primary effectiveness endpoint findings, Krucoff said.
During 12 months of follow-up, bleeding risk of varying levels were similar in both groups.
“This identified a high bleeding risk group just like in LEADERS FREE,” Krucoff said. “By enrolling more than half of the patients in North America, this supports the generalizability of the findings of both studies in patients on both sides of the Atlantic,” Krucoff said. – by Darlene Dobkowski
Reference:
Krucoff MW, et al. Late-Breaking Clinical Trials 1. Presented at: TCT Scientific Symposium; Sept. 21-25, 2018; San Diego.
Disclosures: The study was funded by Biosensors International. Krucoff reports he received grant/research support and consultant fees/honoraria from Abbott Vascular, Biosensors, Boston Scientific, CSI, Medtronic, OrbusNeich and Terumo.
Perspective
Back to Top
The biolimus stent is an interesting stent. It is a little bit different because it is a drug-coated stent, but there is no polymer coating on the stent itself.
Having said that though, the stent appears to be safe and to have advantages that so far we have not necessarily seen in other stents were not well proven. That is specifically in reference to this study. They were able to use only 30-day DAPT in the patients with high bleeding risk, then they were able to stop that and they still had great outcomes at 1 year for this stent. That is an advantage for patients who are on oral anticoagulation who are elderly, who have renal failure or who have previous bleeding conditions or the tendency to bleed. With this stent, they only need DAPT for 1 month, so therefore, they can reduce their bleeding risk, but yet at 1 year, they still had a very safe outcome. They also had good outcomes in terms of what we expect from other DES in terms of reduced re-narrowing or restenosis.
This is one of many second- and third-generation DES showing improved outcomes. They are getting better with their strut thickness and design. It is very important that we know now that smaller struts are safer. Secondly, if we have less inflammatory response from the stent or the polymer, then that is safer too for patients. Finally, if that is true, then maybe we do not have to use DAPT as long, and therefore, we can use these stents in more patients.
The researchers’ major goals of the study and the presentation is that it is a safe stent and will the FDA approve it. This gives them good evidence that it is a safe stent that they could approve and would then be in the armamentarium with other stents that are out there.
Why would someone use it? They want it to be used in patients in general because it is a safe and effective drug-coated stent, and then secondly, it may also even be better than other stents or at least it has evidence that it can be very safe in these high bleeding risk patients.
We see them quite a lot, particularly in the elderly. Atrial fibrillation is so prominent in all our populations and anticoagulation is so important to them, so if we can find stents where we have fewer antithrombotic drugs on board, then hopefully they can have their stent without the risk for increased bleeding.
The only other concern is that there was a little bit higher stent thrombosis rate than we are used to seeing at the 1% range. There are a couple of factors there, one is that this particular stent is different in that we have not seen biolimus in the other stents before. They say that there are features of it that make it safer. That remains to be seen, but because it is just applied directly on that stent with no polymer or anything to mete out the absorption over time — it is all gone within 30 days — that may be part of the reason that they had a higher stent thrombosis rate. That is something that is of concern and needs to be further looked into to make sure that it is safe.
Perspective
Back to Top
This is a very important study because we are starting to see these high bleeding risk patients more in our practice. The population is aging and the comorbidities are going up. Many times, these patients are turned down for bypass surgery because of their comorbidities.
We need to see more studies that include those patients. That’s going to require a push on the clinical community, not the industry because the industry has obvious reservations about that. These patients die from all types of causes. As a clinical community, we’re going to have to push to do more studies in this population.