Bioresorbable Scaffolds Stumble While Current DES Hold Strong

Tricia Ward


November 11, 2016

At the recent Transcatheter Cardiovascular Therapeutics (TCT) meeting, a common "complaint" voiced during presentations on stents with bioresorbable polymers and stents that dissolve entirely was that results for current-generation permanent polymer drug-eluting stents (DES) are so good that it's difficult to show meaningful differences with the new technologies. The data so far suggest that bioresorbable-polymer stents are on par with durable-polymer DES, but the promise of the bioresorbable vascular scaffold showed signs of collapse.

ABSORB II Misses the Mark

The US Food and Drug Administration (FDA) approval of the Absorb bioresorbable vascular scaffold (BVS) (Abbott Vascular; Santa Clara, California) has been controversial given the more complex implant procedure and trends toward higher rates of stent/scaffold thrombosis compared with current DES.[1] The pro-BVS argument was that any early disadvantages would be offset by long-term gains, including improved vasomotion, with the ABSORB II 3-year results, touted as a test of that proof of concept. However, the BVS did not pass the test and failed to meet the mechanistic co-primary endpoint of superior vasomotor reactivity compared with an everolimus-eluting stent (EES). More concerning was the higher late lumen loss and scaffold thrombosis seen with the bioresorbable platform.

Medscape spoke to cardiologists experienced with these devices for their reaction. When ABSORB III data were presented at TCT in 2015, Dean J. Kereiakes, MD (Christ Hospital Heart and Vascular Center, Cincinnati, Ohio), said that "the entire concept, the design of this device, is improved late outcomes."

[Current-generation DES] made the job so easy that interventionalists have become sloppy

In a phone interview, Dr Kereiakes's responded to the disappointing ABSORB II data by saying, "At the very least, this pushes the time course back for potential benefit," noting that the device was still present at 2-3 years. He said that the limitations are in large part explained by this being a first-generation device that may become obsolete in the next couple of years. Dr Kereiakes remains optimistic about the technology as a whole, based on the 5-year optical coherence tomography data.[2] "If I get a stent," he said, "I want my artery to look like that."

In an email to Medscape, Dr Robert Byrne (Deutsches Herzzentrum Munich, Munich, Germany) also mentioned the longer-than-anticipated resorption timeframe to explain the ABSORB II findings. "In our practice, we have seen patients at 3-year follow-up with scaffolds that are clearly still visible on intravascular imaging. I don't know if benefit would be detectable if a 5-year time point were chosen or if an imaging modality other than QCA [quantitative coronary angiography] were used. However, this is something of a moot point in view of the poorer clinical outcomes."

Poor implantation technique was blamed as a major contributor to the worse outcomes. Dr Kereiakes went so far as to say that current-generation DES have "made the job so easy that interventionalists have become sloppy." How could poor implantation be tied to late events at the time of intraluminal scaffold dismantling (ie, when the stent resorbs)? "If you have endothelial coverage of the device, it remains endoluminal; but if you don't, they [the struts] can fall into the lumen," he explained.

Azeem Latib, MB BCh (San Raffaele Hospital, Milan, Italy) described the ABSORB II 3-year findings as "disappointing to say the least, and also a little bit worrisome as regards late events." He, too, thought that poor technique including underexpansion was the probable cause of late events when the struts dissolve/dismantle. He questioned whether QCA was the best way to measure vasomotion because there was surprising evidence of improvement in the metallic stent arm. The endpoint was assessed by angiographic measurements of the vessel wall diameter in the stented region before and after the administration of a vasodilator (nitrate), and comparing these values with preimplantation measurements. "In the future, we may need to consider using intracoronary imaging," added Dr Latib.

He is personally reassured by the Milan 4-year experience implanting BVS; they have not seen late events or any warning signals. "If there are late events despite good technique, then you could say there is something wrong with the technology...I don't think we're quite there." He explained that at his institution they call all patients with BVS on a quarterly basis to see how they're doing and that they are vigilant about technique and the liberal use of intracoronary imaging at the end of the procedure.

How will the latest findings inform discussions with patients? Dr Latib will tell his patients that it may take longer than 3 years to see advantages for bioresorbable stents, and he will discuss extending dual antiplatelet therapy (DAPT) beyond 1 year. In ABSORB II, the patients with late or very late scaffold thrombosis were not on DAPT. Dr Kereiakes continues to enroll patients in ABSORB IV, which mandates high-pressure post dilatation. When consenting patients, he discusses the fact that the risk for thrombotic events may be slightly higher, requiring longer use of DAPT.

Both Drs Latib and Kereiakes want to see more long-term data on the BVS and anticipate earlier-than-planned unblinding of ABSORB III to address some of the concerns. They are also optimistic that next-generation investigational bioresorbable stents with smaller struts and a more rapid resorption profile may have better outcomes.

In-Stent Restenosis: Leave No Metal Behind

Bioresorbable stents were assessed for in-stent restenosis (ISR) in the RIBS VI registry, which compared BVS with matched historical controls treated with EES. The data showed that the regular DES had better angiographic results than the bioresorbable scaffold in a complex patient population treated with an aggressive implantation technique.

Undeterred, lead investigator Fernando Alfonso, MD, PhD, is pursuing the RIBS VI scoring study which will implant BVS after preparation of the ISR lesion with a scoring balloon. Both Drs Byrne and Kereiakes remain convinced that the "leave no metal" behind strategy is the future of ISR management.

"The implantation of multiple stent layers is clearly not desirable, and observational data and clinical trial experience point towards an excess of late adverse events in patients treated with a stent-in-stent approach," wrote Dr Byrne, citing data from ISAR-DESIRE 3[3] among others. But he is not persuaded that bioresorbable stents will meet this need "in a setting where full expansion of the scaffold might be difficult to achieve...our preferred option—assuming that the mechanical integrity of the original stent is intact (ie, no fracture)—is to treat these patients with drug-coated balloon angioplasty."

Bioresorbable Polymers and the Healing Hypothesis

Suggestions that permanent polymers may be linked to delayed healing, increased inflammation and neoatherosclerosis (new atherosclerosis inside the stent) fueled the development of stents with bioresorbable polymers. At TCT, the BIO-RESORT study comparing two such stents—the FDA-approved SYNERGY™ stent (Boston Scientific; Marlborough, Massachusetts), and the CE-mark Orsiro stent (Biotronik; Bülach, Switzerland)—against a permanent polymer zotarolimus-eluting stent ZES did not show any difference between the three platforms.

TRANSFORM-OCT used optical coherence tomography imaging to compare stent coverage and neoatherosclerosis for the SYNERGY stent and a durable-polymer ZES. The results were similar for both stents at 3 months when the bioresorbable polymer was still around, and at 18 months when it was long gone. The optical coherence tomography images revealed excellent coverage for both stents and similarly low rates of neoatherosclerosis (percentage of frames with in-stent lipid-laden neointima). The presenter, Giulio Guagliumi, MD (Papa Giovanni XXIII, Bergamo, Italy), concluded that "it remains unclear whether longer-term follow-up may reveal differential healing characteristics of contemporary DES."

Dr Byrne thinks that the two studies confirm prior data that stents with bioresorbable polymers are comparable to current technologies in the short term. "Whether late adverse events—many related to neoatherosclerosis—can be reduced remains to be assessed by following these patients long-term. In my opinion, a timeline of follow-up of at least 5 years is required. In fact, for otherwise healthy patients affected by coronary disease in middle age, even longer-term outcomes are what matter," he wrote.

Non-stent-related Outcomes Poorer in Women and Minorities

Of course, stent type is not the only factor affecting patient outcomes. Dr Guagliumi postulated that optimal medical therapy with high-intensity statins might be key for limiting neoatherosclerosis and may explain the good results of TRANSFORM-OCT.

To continue just putting metal into patients' coronary arteries cannot be the best we can do.

Seeing the patient picture beyond the stent was addressed in PLATINUM Diversity, a novel observational trial that enrolled an enriched all-comers cohort of women and minorities undergoing PCI. After adjustment for baseline differences among the populations, outcomes were worse for women and minorities compared with a historical control population of white men. However, lead investigator Wayne Batchelor, MD (Tallahassee Memorial Healthcare, Tallahassee, Florida), noted that stent thrombosis and target vessel revascularization were comparable among the three groups, suggesting that any differences in outcomes are unrelated to the stent technology.

With that in mind, Medscape asked whether current-generation DES are good enough and whether research dollars would be better invested in other strategies to improve outcomes. Dr Kereiakes commented that many people said the same thing about the NASA space project. Dr Latib was also in favor of continuing the pursuit for better stent technology. "To continue just putting metal into patients' coronary arteries cannot be the best we can do."

Follow Tricia Ward on Twitter: @_triciaward

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Editor's Note: An earlier version of this article incorrectly stated that the durable-polymer stent in BIO-RESORT and TRANSFORM-OCT was an everolimus-eluting stent; in fact it was a zotarolimus-eluting stent

Disclosures: Dr Kereiakes is a consultant for Abbott Vascular, Boston Scientific Corporation, and Svelte Medical Systems, Inc., and serves on the scientific advisory board of HCRI, Ablative Solutions, Inc., Boston Scientific Corporation, and Abbott Vascular. Dr Byrne has received lecture fees from B. Braun Melsungen, AG; Biotronik; and Boston Scientific; and institutional research grants from Heart Flow and Boston Scientific. Dr Latib reported no relevant financial relationships.


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