Absorb Data Show Bioresorbable Stent Noninferior to Current Standard of Care: ABSORB III and More

October 13, 2015

SAN FRANCISCO, CA — A head-to-head comparison of the everolimus-eluting stent with a bioresorbable scaffold (Absorb, Abbott Vascular) against a conventional everolimus-eluting cobalt-chromium stent (Xience, Abbot Vascular) showed the two devices yielded similar rates of target lesion failure (TLF) at 1 year.

TLF, a composite end point that included cardiac death, target vessel MI, or ischemia-driven target lesion revascularization, occurred in 7.8% of patients who received the "vanishing" stent compared with 6.1% of patients who received the conventional Xience stent (P=0.007 for noninferiority).

Like the primary end point, the individual components of the TLF end point were numerically larger with the Absorb stent but did not reach statistical significance. Regarding other adverse outcomes, device thrombosis occurred in 1.5% of the Absorb-treated patients and 0.7% in patients who received the Xience stent, a difference that was also not statistically significant.

Dr Dean Kereiakes

The study, known as ABSORB III, was presented yesterday at TCT 2015 by co–principal investigator Dr Dean Kereiakes (Christ Heart and Vascular Center, Cincinnati, OH) and published simultaneously in the New England Journal of Medicine[1]. Although the Absorb stent is not yet approved by the US Food and Drug Administration—it is currently available in Europe—Kereiakes made the case for the absorbable scaffold.

"The entire concept, the design of this device, is improved late outcomes," Kereiakes said. "What is undeniable is that there is a durable hazard of device-related events after the very best metal platform [drug-eluting stents] that we have today."

That durable hazard—recorded as either TLF or device-related events—is in the range of 2% to 3% per year as documented in multiple registries, said Kereiakes. The reason for the hazard is believed to be late healing/inflammation, neoatherosclerosis, or stent fracture, and while it is still a "leap of faith," the hope is that a stent that is completely absorbed by the body in the months after opening an occluded artery will prevent these late adverse events.

"There is only one way for a metallic scaffold to respond over time and that's to become narrower," said Kereiakes.

Lots of Data to ABSORB

The ABSORB III study is a large, multicenter, randomized trial with 2008 patients with stable or unstable angina and up to two de novo lesions randomized in 2:1 fashion to the Absorb or Xience stents. In total, 1322 patients received the Absorb stent with bioresorbable scaffold and 686 patients received the Xience stent.

Designed as a noninferiority trial, the 1-year rate of TLF among patients treated with the Absorb stent was noninferior to rates among those who received the Xience stent. Similarly, rates of cardiac death, target vessel MI, and ischemia-driven target lesion revascularization were similar with the two stents. Rates of angina, ischemia-driven target vessel revascularization, and all revascularization, which were tested for superiority, failed to show an advantage of the Absorb stent over the Xience stent.

Safety and Efficacy Outcomes at 1 Year

Outcome Absorb, n=1322 (%) Xience, n=686 (%) P
Target lesion failure 7.8 6.1 0.16
Cardiac death 0.6 0.1 0.29
Target vessel MI 6.0 4.6 0.18
Ischemia-driven target lesion revascularization 3.0 2.5 0.50
Ischemia-driven target vessel revascularization 5.0 3.7 0.18
Patient-reported angina 18.3 18.4 0.93
Definite or probable device thrombosis 1.5 0.7 0.13

Commenting on the results, Kereiakes said the Absorb stent is a first-generation device with relatively thick stent struts (150 μm) and is somewhat trickier for operators to implant. Despite this, results showed the Absorb stent is comparable to the Xience stent, a device that is considered the gold standard.

Regarding the rates of device thrombosis, which occurred twice as frequently with the new stent compared with Xience, he said the ABSORB III researchers conducted an analysis of outcomes in small vessels. If vessels with a reference diameter less than 2.25 mm were excluded, the rates of device thrombosis were 0.9% in the Absorb arm and 0.6% in the Xience arm.

"It's a neck-to-neck, toe-to-toe race with a generation-one device," said Kereiakes. "That's what is really remarkable and makes me really comfortable as an interventionalist putting [Absorb] in."

Interpreting the Results

Dr Dan Simon (University Hospitals Case Medical Center, Cleveland, OH), who was not affiliated with ABSORB III, said advances in technology and its various iterations tend to cost more money, but researchers and clinicians are still learning what the incremental advantages of the Absorb stent might be.

"Clearly, this trial doesn't deliver a message that there is a patient-centered outcome benefit," said Simon, noting that rates of angina were similar between the Absorb- and Xience-treatment arms. "The long and the short of it is that we'll pay a little more for a device that patients are asking for because they are concerned about rigid cages and access to bypass down the line."

In an editorial[2], Dr Robert Byrne (Deutsches Herzzentrum/Technische Universität, Munich, Germany) writes that while ABSORB III was designed in consultation with the FDA, the noninferiority margin used in the trial is large, at 4.5% against the background rate of TLF of 6.0% with the Xience stent. To heartwire from Medscape, Byrne noted that if the margin of noninferiority were narrower, a larger study would have been required.

"This means you have to interpret the clinical significance of the findings with some caution, because most clinicians wouldn't accept this degree of difference between the two stents in their catheterization laboratories," said Byrne.

Like others, Byrne noted the point estimates for the individual components of the primary end point favored the conventional Xience stent, even if just numerically.

"Altogether, we need to have a balance sheet," Byrne told heartwire . "These stents are little bit more technically challenging to implant. They seem to have a slightly higher rate of adverse clinical events, which wasn't significant in this study, and there's going to be a cost differential. You have to put all of things into perspective and you ask yourself, 'Is the hypothesis that these stents are better than conventional stents enough to convince me to use them, or do I need to have tangible evidence in terms of improved late outcomes before I switch to this technology?' "

Byrne, an interventional cardiologist, says Absorb has been available in Europe since 2011 and patient selection remains key, noting those with large amounts of coronary calcification or bifurcation lesions are not good candidates. All things considered, he believes Absorb is a good stent choice in approximately 10% to 15% of patients. As the technology improves, he expects this number to increase.

The ABSORB China Trial

Dr Runlin Gao

Also on Monday, the first of the TCT 2015 late-breaking clinical-trials sessions, Dr Runlin Gao (Chinese Academy of Medical Sciences, Beijing) presented data from ABSORB China, a study designed for regulatory approval and one that included a primary end point of in-segment late loss at 1 year. In the study, 480 patients were randomized to either the Absorb everolimus-eluting stent with the bioresorbable scaffold (n=241) or to the Xience everolimus-eluting cobalt-chromium stent (n=239).

At 1 year, in-segment late loss, the study's primary end point, was 0.19 mm among patients who received the Absorb stent and 0.13 mm for those treated with the Xience stent. Again, this difference was not statistically significant. On quantitative coronary angiography (QCA), in-device mean lumen diameter (MLD), in-device percent diameter stenosis, and in-device late loss were all significantly worse with the Absorb stent, although the same measures assessed "in-segment" were no different between the two stents.

Dr Bernard Chevalier

In addition, Dr Bernard Chevalier (Institut Jacques Cartier, Massy, France) presented 2-year data from the ABSORB II study, a trial that was first presented at TCT 2014 and reported by heartwire at that time.

At 2 years, the rate of device-oriented composite outcomes, which included cardiac death, target vessel MI, and clinically indicated target lesion revascularization, was 7.0% among the patients who received the Absorb stent and 3.0% among those treated with Xience (P=0.07). The rate of target vessel failure, which included cardiac death, MI, and clinically indicated target vessel revascularization, was 8.5% and 6.7% among the Absorb- and Xience-treated patients, respectively (P=0.48).

Taken together, the ABSORB II and ABSORB III studies showed the Absorb stent was noninferior to the Xience stent in terms of TLF, but experts say it is still too early to show any advantage of the Absorb stent. A benefit, if one is to emerge, will likely be observed in the longer term, say the experts.

"The potential benefit you can expect from this technology will take place after the full absorption of the device," said Chevalier. The data at 1 and 2 years, he added, remain reassuring, and he expects to see a benefit of the vanishing scaffold at 3 years and beyond.

To the media, Simon stressed the stent represents an attempt to fill an unmet need for patients. With conventional stents, including the best in class, the 5-year rates of TLF can be as high as 17%, with approximately half of these late events attributed to the stent.

"We have a need to do better for our patients," said Simon.

Kereiakes reports consulting for Harvard Clinical Research Institute, Boston Scientific, Abbott Vascular, Svelte Medical Systems, Janssen, Sanofi, and Ablative Solutions; disclosures for the coauthors are listed on the journal website. Byrne reports speaker fees from Braun Melsungen, Biotronik, and Boston Scientific. Gao reports a research grant from Abbott Vascular. Chevalier is a consultant for Abbott Vascular.

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