LEADERS FREE: Polymer-Free DES Maintains Superior Safety, Efficacy Over BMS at 2 Years

WASHINGTON, DC—Among patients at high risk for bleeding, 2-year results of a novel, polymer-free drug-coated stent (DCS) show sustained superiority with regard to safety and efficacy compared with a BMS when both were followed by 1 month of DAPT.

The findings reflect what was presented at 1 year for the LEADERS FREE trial at TCT 2015, but questions have lingered as to whether longer-term results would show sustained benefit with the newer device.

The 2-year results are “one more nail in the coffin of BMS,” said Dean J. Kereiakes, MD (Christ Hospital, Cincinnati, OH), in an email to TCTMD, echoing a phrase he used a year ago after seeing similar findings for DES versus BMS in a propensity-matched analysis of the DAPT Study. Even since then, “use of BMS has been buoyed up by fear of liability created by the ‘myth’ of shorter DAPT duration requirement that has been perpetuated by outdated practice guidelines,” added Kereiakes, who was not involved in the study.

Study presenter Philip M. Urban, MD (LaTour Hospital, Geneva, Switzerland), used the same expression, telling TCTMD that these results are “the [final] nail in the BMS coffin.” That’s despite the recent results of the NORSTENT trial, which found no difference in the primary endpoint of death/nonfatal spontaneous MI between modern BMS and DES at 5 years in patients with stable or unstable coronary artery disease but saw significantly reduced revascularization rates for DES. Urban said that even though the BMS patients in NORSTENT received 9 months of DAPT, the findings do not “contradict LEADERS FREE at all.”

“If you take more complicated patients, sicker patients, then an active stent does better with short DAPT, which is the only real reason why you want to use a BMS in the first place,” Urban observed. “I just don't see why anyone would still want to use a bare-metal stent. They're falling off the shelves in Europe fast. Many hospitals don't have any anymore or just a couple.”

Superiority Sustained

The trial originally randomized 2,466 patients with high bleeding risk scheduled for PCI to received either the BioFreedom DCS (n = 1,239) or the Gazelle BMS (n = 1,227; both Biosensors International) plus 1 month of DAPT. The 2-year results confirm superiority for both the primary safety endpoint (cardiac death, MI, or stent thrombosis) and the primary efficacy endpoint (clinically driven TLR).

Outcomes at 2 Years

There were no differences in major bleeding between the DCS (8.9%) and BMS arms (9.2%; P = 0.95), and BMS patients were slightly more likely to report a coronary thrombotic event (8.2% vs 10.6%; P = 0.045). Congestive heart failure, multivessel disease, number of stents, and stent type were factors associated with the primary safety endpoint events; planned oral anticoagulation and raised plasma creatinine were associated with bleeding events; and age > 75 years and low hemoglobin were linked with both endpoints.

All-cause mortality (13.1% vs 13.8%; HR 0.94; 95% CI 0.75-1.17) and cardiac mortality (6.6% vs 6.9%; HR 0.94; 95% CI 0.69-1.28) were also similar between the DCS and BMS groups at 2 years.

In the year since the first LEADERS FREE results were presented, Urban said the perception of BMS use among interventional cardiologists has changed. “It's a process because it was quite a lot to swallow for the interventional community,” he explained. “They had to grasp the concept of an active stent with only one month [DAPT], which is a bit of a shocker in a way, and then try and understand who these high bleeding risk patients are. . . . It's definitely having an impact and the company is selling a lot more of these stents than it was a year ago, but I think it will still continue to increase somewhat over the next year or two.

‘Irresponsible’ to Say BMS Have No Role

In a press conference, Neal Kleiman, MD (Houston Methodist DeBakey Heart and Vascular Institute, TX), admitted he was surprised by the LEADERS FREE results at 1 year but “less surprised” and “delighted” by the 2-year findings. “The one thing that is in contrast to the other trials we’re seeing is higher ischemic event rates,” he said. “But remember when you select a group at high risk for bleeding you are also selecting a group that is [also] at high risk for thrombotic events.”

Amidst all the excitement for this device, moderator Ajay Kirtane, MD, SM (NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, NY), noted that although the results seen with the BioFreedom DCS—which received European CE Mark approval in January 2013—are appealing, it is not yet available in the United States. The US Food and Drug Administration gave Investigational Device Exemption to its manufacturer in 2014 for a feasibility trial, which is still ongoing and will require 3 months of DAPT after implantation.

“In the US population, it’s a little bit irresponsible right now to say that there's no reason or no role for bare-metal stents,” Kirtane said. “I don't say we don’t use them at all, . . . but there is a very, very small niche for it.”

In agreement, panelist Paul Teirstein, MD (Scripps Clinic, La Jolla, CA), noted that while he can’t remember using a BMS within the last year, he “would probably” use one if treating a patient who needed another operation in 3 weeks.

High-Risk Population Allows for Different Perspective

As for the patient population at high-risk for bleeding, Urban said it’s likely these individuals will appear more often in trials going forward. “In fact, I'm aware of 10 trials looking at DAPT durations of 3 months or less that are actually ongoing . . . with four on high-bleeding risk patients,” he told TCTMD. “So within the next 2 or 3 years we'll be learning a lot more.”

Specifically, Urban said, it will be interesting to investigate whether “the rapid drug elution from the stent into the wall is an important parameter or [if it’s] just something that's there and doesn't really matter. . . . Whether a stent that elutes over a period of 3 months is safe with 1-month DAPT, somehow it's a disconnect to me. You're still hitting the vessel with drugs, but you're already pulling out. But maybe it's perfectly safe. We'll see.”

Kleiman asserted that this is “clearly a population that needs something better than what we have, unlike the other populations that we've seen.”

“The key,” said Kirtane, “is that [we need] to do studies in this patient population because it informs routine clinical practice. That's the biggest take home, and . . . it can’t be overemphasized how important that is.”

Image credit: Biosensors International.