Drug-eluting bioresorbable vascular scaffolds proved to be noninferior to best-in-class drug-eluting stents at one year for target lesion failure in a randomized clinical trial. The data were sufficient to earn the support of a U.S. FDA advisory panel, but will “as good” be good enough to win over cardiologists and payers?
The multicenter, randomized controlled clinical trial ABSORB III was designed to evaluate the safety and effectiveness of a device that potentially offers the benefits of a stent without its permanence. Sponsored by Abbott Vascular, the trial enrolled 2,008 patients at 193 sites with stable or unstable angina and relatively simple coronary lesions to be treated with either Abbott’s everolimus-eluting polymer scaffold (Absorb) or its everolimus-eluting cobalt-chromium stent (Xience). One-year results, unveiled in late 2015, met the bar set by the FDA for noninferiority for the primary endpoint.
The one-year rate of target lesion failure, defined as the composite of cardiac death, target vessel myocardial infarction (MI) or ischemia-driven target lesion revascularization, totaled 7.8 percent for Absorb and 6.1 percent for Xience (N Engl J Med 2015;373:1905-1915). The 1.7 percentage point difference was within the prespecified noninferiority margin. Xience also edged out Absorb on death from any cause, any MI, any revascularization and definite or probable device thrombosis. The two devices more or less tied for patient-reported angina.
“The fact that it is numerically different by a nonsignificant degree is not surprising,” says Dean J. Kereiakes, MD, medical director at the Christ Hospital Heart and Vascular Center in Cincinnati and a co-principal investigator in ABSORB III. At least at the outset, first-generation bioresorbable scaffolds may be handicapped compared with the latest-generation drug-eluting stents. To provide radial strength equivalent to a metal stent, the polymer-based scaffold requires relatively thicker struts—150 microns vs. less than 100 microns for Xience—plus another 7 microns for the coating that elutes everolimus. “I thought a wider, thicker strut would be associated with greater incidence of periprocedural MI. It wasn’t.”
The two devices virtually tied for MI during a procedure. But the one-year rate of device thrombosis was twice as high with Absorb, at 1.5 percent vs. 0.7 percent with Xience.
“Bioresorbable scaffolds, with devices now being first generation, are somewhat thicker strut devices compared with current contemporary drug-eluting stents and for that reason they are prone to a slightly higher rate of stent thrombosis unless they are implanted really well,” says Gregg Stone, MD, of Columbia University Medical Center in New York City and ABSORB III study chair. “I do believe you can overcome most of any increased risk, but it does require a little bit more attention to operator technique.”
Lessons & learning curves
The one-year results gave researchers insights about the device’s learning curve and other physician factors. The average operator in the trial deployed two scaffolds in the trial, Stone says, and the device’s deployment technique and profile differ from metallic stents. “You can be a moderately high-volume operator and be surprised when you put the device in by its profile,” Kereiakes says. “It is not a big deal for those of us who have tried all types of devices, basically test-pilot devices, but it is very different from putting the Xience stent in.”
Kereiakes, Stone and co-principal investigator Stephen G. Ellis, MD, of the Cleveland Clinic, reviewed every case of scaffold thrombosis and identified some common themes, many related to deviations from the study protocol. For instance, 20 percent of the lesions in patients enrolled in ABSORB III were below the 2.5 mm lower limit for the reference vessel diameter, according to Stone.
“That is really where the stent thromboses clustered, which is not surprising given that when you have a very thick strut device and you put it in a very small vessel, you magnify any of these space-occupying concerns with the technology,” Stone says. “If you look at the larger vessels, the ones for which the device was intended, then the stent thrombosis rates and the overall outcomes were very similar between Absorb and Xience.”
The study recommended that operators use high-pressure postdilation with a noncompliant balloon, with the goal of 10 percent or less residual stenosis. Instead, in the cases