Absorb BVS: Safety, Efficacy, and Stent Thrombosis Tackled in Two New Analyses

Two new meta-analyses evaluating the safety and effectiveness of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) suggest the “dissolving” stent is as safe and effective as an existing everolimus-eluting cobalt-chromium stent, although there are some important caveats. 

In the first meta-analysis, published in the March 26, 2016, issue of the Lancet, the researchers pooled data from four randomized trials—ABSORB China, ABSORB Japan, ABSORB II and III—and report that the “patient-oriented” endpoint, a composite of death, MI, or coronary revascularization, was comparable between 2,164 patients who received the Absorb stent and 1,225 individuals who received the Xience stent (both Abbott Vascular).

While the mortality and coronary revascularization rates also were nearly equivalent between patients treated with Absorb and Xience, there was a trend toward a higher rate of MI in the Absorb group.

Definite or probable device thrombosis occurred in approximately twice as many patients treated with Absorb as with Xience, although this difference was not statistically significant.

“There is a clear signal present for an approximate doubling of the rate of scaffold thrombosis compared with the metallic drug-eluting stent, Xience, which I do believe was real, as practiced in these clinical trials,” lead investigator Gregg Stone, MD (Columbia University Medical Center, New York, NY), told TCTMD. “However, the difference in the absolute rate is relatively small, and what we’ve learned from ABSORB III is that most of the excess scaffold thrombosis events are clustered in the very small vessels for which the device isn’t intended.”

Stone said he believes the risk of scaffold thrombosis can be mitigated with an Absorb-specific deployment protocol, one that wasn’t in place when the early trials were conducted. Since those landmark studies, investigators have learned the importance of placing the stent in appropriately sized vessels and preparing the lesion with predilatation and/or lesion modification. Postdilatation with high-pressure, noncompliant balloons and the liberal use of intravascular imaging are also highly encouraged.

“If all these techniques are followed, we believe the scaffold thrombosis rate is similar to the best-in-class Xience metallic, drug-eluting stent,” said Stone. “There is a definite learning curve here, both in terms of technique and experience. It should also be emphasized that nearly all these operators in these randomized trials, particularly ABSORB III, used the device for the first time within the clinical trial setting.”

Overall, the researchers consider the results from the meta-analysis encouraging, said Stone.

Expanded Meta-Analysis

In the second meta-analysis, performed by stone, MD (New York University School of Medicine), and colleagues and published online March 21, 2016, in the International Journal of Cardiology, the researchers analyzed six randomized trials. These included the four studies included in the meta-analysis by Stone and colleagues plus TROFI II, a trial that included STEMI patients who received the Absorb stent within 24 hours of symptom onset, and EVERBIO II, an all-comers study that included ACS patients with complex lesions. 

Overall, 3,738 patients were enrolled in the six studies. Compared with the use of an everolimus-eluting stent, the Absorb stent was associated with similar risks of target lesion and target vessel revascularization, as well as similar rates of death and cardiovascular death. There was a trend toward a higher rate of MI with the Absorb stent (RR 1.35; 95% CI 0.98-1.86).

Like in the Lancet analysis, there was an approximate two-fold higher risk of scaffold thrombosis with Absorb compared with Xience (RR 2.11; 95% CI 0.99-4.47). Bangalore told TCTMD that they tested the association in five statistical models, and only in one model was the increased risk of scaffold thrombosis statistically significant. Moreover, the researchers say the accumulated sample size is too small to make any firm conclusions about the risk of scaffold thrombosis, noting that nearly 60,000 patients would be required to show a 30% increase with Absorb.

Still, Bangalore said that given the numerical increase in scaffold thrombosis with Absorb, physicians need to be careful with the device when implanting.

“It’s good for people to know that we’re dealing with a scaffold that’s very thick,” he said. “It brings us back to the Cypher era where the stent struts were very thick. We know from many of the studies that it does matter how thick the stent struts are when it comes to stent thrombosis. That’s why we have to be careful. With the numerical increase [in scaffold thrombosis], I would say we have to be meticulous in the way we deploy the stents.”

The researchers report that the risk of scaffold thrombosis with Absorb was reduced in clinical trials where operators were more likely to use postdilatation after implantation and in trials with a lower proportion of ACS patients enrolled.

Long Lineage of Studies Analyzing Absorb

Approved for use in Europe, the Absorb BVS system consists of an absorbable polymeric scaffold and polymer, both of which are completely broken down and dissolved within 36 months of implantation. The new data are the latest in a series of reports, including two previous meta-analyses, evaluating the safety and efficacy of the Absorb stent, all of which were reported by TCTMD. And like the latest studies, those earlier meta-analyses also suggested a two-fold higher risk of scaffold thrombosis with Absorb.  

David Cohen, MD (St. Luke’s Mid America Heart Institute, Kansas City, MO), who was not involved in the analyses, told TCTMD the stent thrombosis finding remains “concerning,” even if it is explainable by several factors. Acute and subacute thromboses, which represent the excess of events, are associated with major MIs and high fatality rates. “Even small excesses of those serious events are important to understand and recognize,” said Cohen.

The Absorb stent, he added, is a more challenging device to use and therefore “puts more of a premium on the operator to do everything perfect.” In such cases where not everything can be done perfectly, there is less margin for error with the device compared with conventional DES. And while operators can take steps to mitigate the risks of scaffold thrombosis, Cohen said this highlights the shortcomings of first-generation Absorb bioresorbable scaffold.

“There are things physicians can do to minimize the risks but some of them come with trade-offs, and many of them come with higher costs,” he said. “Part of the job with these devices is to be forgiving. I don’t think it’s entirely fair to point to operator error when a problem happens with the device. Devices have to have a certain amount of forgiveness to account for imperfect operators and imperfect procedures. The more forgiving devices are often superior ones.”

What Does the Future Hold?

Abbott Vascular is currently awaiting a decision from the US Food and Drug Administration (FDA) about device approval. They are seeking an indication for the Absorb stent to improve coronary luminal diameter in patients with ischemic heart disease due to de novo coronary artery disease lesions. The indication would include lesions 24 mm or less in length and vessels with a reference diameter ranging from 2.5 to 3.75 mm.

Two weeks ago, members of the FDA’s Circulatory System Devices Panel voted overwhelmingly in favor of the Absorb stent, with nine of 10 voting members stating they believe the benefits of the dissolving stent outweigh the risks (one panelist abstained from voting on the question of risk versus benefit).

Bangalore said there is promise for the Absorb scaffold, particularly for what can be done down the road. With the scaffold disappearing over time, it leaves physicians future options when treating patients with coronary artery disease. “If we find both the devices are noninferior, that’s something I would take,” said Bangalore, referring to the head-to-head comparison against the best-in-class Xience stent. “I don’t really need the scaffold to be superior. The question right now is, ‘Is it really noninferior?’ Some of the scaffold thrombosis and MI signals would indicate we need to be a bit careful.”

Despite some of the upfront risks, physicians are still waiting for the “payoff” when it comes to bioresorbable stents, added Cohen. The promise of the bioresorbable technology is that it can reduce late vascular consequences associated with a permanent stent, but right now such thinking is purely speculative. “It does make some sense that removing the foreign body will at some point lead to less reaction, but interventional cardiologists have been burned enough by things that made sense that didn’t turn out to be true,” he said.

As for the long-term benefits of what is potentially a “transformative new technology,” Stone said it will take many years to prove in ongoing clinical trials. In the short-term, the device offers practical benefits for patients and physicians. “There just really isn’t any reason to want a permanent metallic device inside a coronary artery that’s not necessary,” he said.

A second-generation bioresorbable scaffold from Abbott—one with considerably thinner stent struts than the current device—is about to start being tested in humans later this year.