In the wake of two-year results from the ongoing multicenter ABSORB III trial, the jury’s still out on the relative merits of the Absorb™ everolimus-eluting bioresorbable vascular scaffold (BVS) versus the Xience metal drug-eluting stent (DES).
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Although outcomes were comparable for the BVS and DES between years 1 and 2, patients receiving the BVS had an overall elevated risk of adverse outcomes at year 2 compared with patients receiving the DES. So reported ABSORB III investigators on March 18 at the American College of Cardiology’s (ACC) Annual Scientific Session. The elevated risk with the BVS appears to be attributable to placement of the bioresorbable scaffold in vessels that were smaller than currently recommended, notes Cleveland Clinic’s Stephen Ellis, MD, lead investigator of ABSORB III.
“A key take-home is that this bioresorbable device shouldn’t be used in very small vessels,” says Dr. Ellis. “These results show that the BVS is generally comparable to the Xience DES when the device is placed in appropriately sized vessels using appropriate procedural techniques. Beyond that, we don’t yet have firm data to suggest whether it’s as good as or better than a contemporary second-generation DES.”
He adds that definitive word on this broader question may not come until results start emerging from the ABSORB IV trial, which is currently enrolling patients.
The ACC presentation follows publication of one-year results from the ABSORB III trial in New England Journal of Medicine in late 2015, which showed the BVS to be noninferior to the DES on the study’s primary end point — target lesion failure as measured by a composite of cardiac death, target lesion MI and ischemia-driven target lesion revascularization — at 12 months.
The new results show that the two treatment arms remained statistically similar for the primary end point during the period between years 1 and 2; however, at the end of year 2, the BVS was associated with a significantly higher risk of target lesion failure (10.9 percent) compared with the DES (7.8 percent) among the trial’s 2,008 patients, who were randomized to BVS or DES therapy on a 2:1 basis.
The difference at year 2 was driven primarily by target vessel MI, which occurred in 7.3 percent of BVS recipients versus 4.9 percent of DES recipients. Rates of cardiac death, ischemia-driven target vessel revascularization and device thrombosis were not significantly different between treatment arms.
The ABSORB III investigators believe some of the adverse outcomes observed in the BVS group may be due to inconsistencies in adherence to study protocols and the procedural techniques used for BVS placement.
They reported that 19 percent of patients in the trial received treatment for vessels smaller than the size range (2.5 to 3.75 mm in diameter) recommended by the study protocol and by FDA-approved labeling for the BVS device. These patients had significantly poorer outcomes than the rest of the study sample, and a subanalysis excluding these patients demonstrated the BVS to be noninferior to the DES on the primary end point at two-year follow-up.
Dr. Ellis explains that the study protocol initially allowed clinicians to determine vessel size based on visual assessment from coronary angiography, which is less precise than quantitative coronary analysis. This accounted for the inclusion of the patients with inappropriately small vessels.
Likewise, the protocol did not specify the use of procedural techniques that have subsequently been shown to improve outcomes with the BVS. “As time went on, data accumulated from various sources to suggest that after we deliver the bioresorbable device to the vessel wall, we should post-dilate it,” he explains. “So during ABSORB III we began to suggest to investigators that they post-dilate.” Yet only about 63 percent of BVS recipients in ABSORB III received post-dilatation.
These recommendations were underscored by a “Dear Doctor” letter issued by the FDA at the time of the ABSORB III presentation at the ACC meeting. That letter reminds operators using the BVS to follow instructions in FDA labeling to avoid its use in small vessels and to adhere to the label’s recommended implantation methods.
Dr. Ellis notes that post-dilatation has been mandated in the new ABSORB IV trial, for which he serves as co-principal investigator. “In ABSORB IV we say that post-dilatation should be performed at high pressure — at least 16 to 18 atmospheres — and the balloon-to-scaffold ratio ought to be at least 1.1 to 1 unless the scaffold appears to be oversized after initial implantation,” he says. “We’re following the moniker PSP — P for predilatation (which we’ve always championed), S for appropriate sizing, and the second P for adequate pressure with post-dilatation.”
These more rigorous protocols are why Dr. Ellis believes ABSORB IV will end up yielding the definitive word on the BVS. “I expect the final word on early safety to come from the one-year results of ABSORB IV, which will likely be reported two years from now,” he says. “The question of whether the bioresorbable device confers a benefit likely won’t be definitively answered until seven years after ABSORB IV recruitment ends — which means early 2025.”
The need for lengthy follow-up stems in part from the fact that the bioresorbable scaffold doesn’t fully dissolve in most patients until year 3. “The value proposition of the BVS is that once the device is fully dissolved after three years, there will be better outcomes,” Dr. Ellis says. “But there are as yet no long-term data from large studies to show that.”
He adds that while three-year results from ABSORB III are expected in fall 2017, they will share the same protocol caveats as the two-year results.
In the meantime, Dr. Ellis says the BVS device, which in July 2016 became the first bioresorbable scaffold approved by the FDA, is a reasonable option for patients who meet the current recommended criteria of appropriately sized vessels (2.5 to 3.75 mm), short lesions, and the absence of unstable angina or acute coronary syndrome.
“The most ideal patient would be a young individual with a longer LAD lesion who you don’t want to send for open-heart surgery out of concern that stenting a large segment of the LAD would block operative access for a future surgery,” he says, noting that other scenarios would be appropriate as well.
He points out that newer-generation bioresorbable scaffolds designed for use in vessels smaller than 2.5 mm are in development, but enrollment in definitive U.S. trials is only beginning. “That means they’re at least three to four years from market approval,” he says.
ABSORB III is funded by Abbott Laboratories, which markets both the Absorb BVS and Xience devices.
Image of the Absorb™ BVS courtesy of Abbott Laboratories.