Biodegradable stents overcome some problems associated with other drug-eluting stents (DES), but advancements in newer durable polymers may give them a run for the money. Bioresorbable scaffolds, which have yet to be approved in the U.S., may be the next disruption facing the market.
Here now, gone tomorrow?
Over the years, stents—first bare-metal, then durable polymer DES and biodegradable polymer DES—have been designed and redesigned to address shortcomings of predecessor technologies. The increased risk of restenosis and revascularization with bare-metal stents, for instance, inspired DES. But the polymer coatings on the latter were thought to trigger inflammatory responses that may contribute to late and very late stent thrombosis, giving durable polymer DES an edge for efficacy but not for long-term safety.
Enter biodegradable stents, whose polymer coatings are designed to be bioabsorbed over time to provide the efficacy of a durable polymer DES and the safety of a bare-metal stent. But in the rat-a-tat world of stent innovation, new iterations with more biocompatible durable polymers, metal alloys and other platforms are challenging biodegradable stents.
“If you look at the first-generation biodegradable stents, it is a leap forward,” says Sripal Bangalore, MD, director of research at the Cardiac Catheterization Laboratory and director of the Cardiovascular Outcomes Group at New York University School of Medicine in New York City. “Technology has advanced faster in the durable polymer arena.”
Bangalore and colleagues performed a mixed treatment meta-analysis to compare the safety and efficacy of biodegradable polymer DES with bare-metal and first- and newer-generation durable polymer DES (BMJ online Nov. 8, 2013). Based on results from 126 randomized trials, they found that biodegradable stents beat first-generation durable polymer stents but not newer generation durable polymer stents for target vessel revascularization.
They concluded that among the newer generation durable polymer stents, cobalt-chromium everolimus-eluting stents offered the best safety and efficacy profile. Their findings were supported in another meta-analysis of 89 trials that concluded biodegradable stents had higher one-year and long-term rates of definite stent thrombosis compared with cobalt-chromium everolimus-eluting stents (J Am Coll Cardiol 2014;63:299-307).
“The concept of the disappearing polymer is questionable in this modern day of stents,” Bangalore says.
From here to eternity
Stenting places a permanent device in coronary arteries for what should be a temporary bridge during healing. As a foreign body, the stent and struts contribute to potential late complications such as thrombosis that then require dual antiplatelet therapy. Its cage structure, designed to prevent early recoiling, remains there for life, interfering with the dynamic physiologic function of the vessel wall.
“You will go in your grave with a piece of metal in your coronary artery,” says Patrick W. Serruys, MD, PhD, of the Thoraxcenter at the Erasmus Medical Center in Rotterdam, the Netherlands. The biological process of restenosis, on the other hand, subsides with time and ceases after a few months. “Since the biological factors of restenosis are operational only for six months, why don’t we put in something that is transient?”
That transient device is the bioresorbable scaffold, he says, which is designed to cover the vessel wall and slowly dissolve over time to be replaced by normal tissue. More than a dozen companies have developed or are developing bioresorbable scaffolds, with two reaching postmarket status in Europe. Those include Abbott Vascular’s everolimus-eluting Absorb and Elixir Medical’s DESolve novolimus-eluting bioresorbable scaffolds. Absorb received CE Mark in 2012 and DESolve in 2013.
Evaluations of the first-generation Absorb device revealed in-stent late luminal loss of 0.44 mm, mostly attributed to reduction in the stent area (Lancet 2008; 371: 899–907). But there was also plaque regression and resumption of pharmacologically induced vasomotion in the scaffolded area. In the second-generation design, which was tested in ABSORB cohort B, Serruys and colleagues found signs of healing, with tissue growth increasing between six months and two years (Circ Cardiovasc Interv 2012 Oct;5:620-632). ABSORB cohort B was designed to test the safety and performance of the Absorb device.
Between two and three years, they reported indications of advanced bioresorption, substantial plaque reduction, no change in late luminal loss and an increase in scaffold area (EuroInterventions online Dec. 3, 2013). The cohort B group had a three-year major adverse cardiac event rate of 10 percent with no scaffold thrombosis and a binary restenosis rate of 6 percent.
Benefits with diversity
The technology has its drawbacks, though. Tensile strength is an issue with polymer devices, operators may need a guidewire to advance the device in a coronary artery and they must carefully inflate the balloon, Serruys says. “It is breakable if you exert too much pressure.”
Dean J. Kereiakes, MD, medical director of the Christ Hospital Heart & Vascular Center and Linder Research Center in Cincinnati and co-principal investigator of ABSORB III, adds that exposure during a procedure may compromise the device. Study protocol mandates an operator discard a device after 15 minutes if it has not yet successfully crossed a lesion. “The reason behind that is the possibility that polymer hydration may reduce the integrity of stent retention and might predispose to stent dislodgement from the delivery system,” he explains.
ABSORB III is a noninferiority trial enrolling about 2,250 patients with up to two de novo native coronary artery lesions in up to two separate vessels who will be randomized for treatment with either the Absorb drug-eluting scaffold or Abbott’s XIENCE stent. Abbott will use the safety and efficacy results in filings with the FDA.
In Europe, interventional cardiologists have been treating more complicated patient populations than are specified in the pivotal ABSORB III study. But Kereiakes does not envision it being as broadly applicable, although he describes its promise as “huge.”
“Several of my European colleagues are trying to use the bioresorbable vascular scaffold platform as a workhorse type device,” he says. “Workhorse in my mind means basically almost every lesion, every day. I don’t think that the current platform is physically capable. It is not as flexible and deliverable.”
Positive results from ABSORB III may give Abbott ammunition for ABSORB IV, which Kereiakes says will be a superiority trial enrolling more complex patients. The trial, if successful, would not only potentially broaden the patient pool in the U.S. but it also would provide evidence to support reimbursement. Anecdotally, some patients in countries where the devices are approved are so eager to be treated with a dissolving scaffold that they pay out of pocket.
Ultimately, the U.S. market may include a mix of stents and scaffolds, and the biodegradable stent may share a seat at the table. Kereiakes also participates in EVOLVE II, Boston Scientific’s pivotal trial to evaluate Synergy, a DES with a bioabsorbable coating. He sees an opportunity for biodegradable stents in the short term and possibly filling other niches in the longer term to treat lesions that are not amenable to bioresorbable scaffolds, or in cases where scaffolding won’t be reimbursed.
“Metal platform devices will not go away,” Kereiakes predicted. “They will continue to be a significant portion of what we do in the future.”