DENVER, CO — New 3-year and 30-day results of trials of the everolimus-eluting, bioresorbable vascular scaffold (Absorb BVS, Abbott Vascular) in the ABSORB III and ABSORB IV trials highlight limitations of the device compared with Abbott’s metal Xience everolimus-eluting stent and potential lessons learned as the first generation of the nonmetal stent technology fails to show an advantage over current stents[1].
In early September, Abbott announced that it was halting worldwide marketing of Absorb, due to reportedly anemic sales. But it’s reasonable to assume that the disappointing 3-year data in ABSORB III and other studies would put a damper on the BVS’s future prospects in any case.
“The original idea was that by removing the permanent implant, the cage, the irritant, that the 2% per year rate of target lesion failure [TLF] that has been seen with all DES after year 1—extending out at least to year 5, and probably beyond—would be mitigated” with a BVS, said co–principal investigator Dr Stephen G Ellis (Cleveland Clinic, OH) here at TCT 2017.
“The value proposition then was that any early excess events perhaps engendered by thicker struts would be offset by better long-term results,” he added.
Although, as previously reported by theheart.org | Medscape Cardiology, ABSORB III at 1 year did meet its primary end point of noninferiority of the BVS for a composite of cardiac death, target vessel MI (TVMI), or ischemia-driven target lesion revascularization (TLR), clinical outcomes at 3 years, the approximate time of complete scaffold bioresorption, paint a different picture.
Between the reporting of the 1- and 2-year results of ABSORB III, case reports began to emerge of very late scaffold thrombosis, “and by the time we reported the 2-year outcomes of ABSORB III, the market had passed its verdict,” Ellis said.
The 3-year clinical outcomes he reported for the first time here will give investigators insight into the excess early risk associated with the use of the BVS and the trajectory of adverse events, but they can’t answer the question of whether patients who receive bioresorbable vascular devices will do better once the scaffolds have vanished compared with patients who receive metallic stents, he noted.
The ABSORB III results were also published online in the Journal of the American College of Cardiology.
ABSORB III
The ABSORB III investigators enrolled 2240 patients with up to two de novo lesions in epicardial vessels, and of the group, 2008 were randomized on a 2:1 basis to receive either the Absorb BVS or Xience stent.
As noted, the trial met its primary end point of noninferiority for TLF at 1 year. The investigators also planned to follow patients in this trial and in the similar ABSORB IV trial with data pooled to test for superiority.
The 3-year rate of TLF with the BVS was 13.4%, compared with 10.4% for the Xience, yielding a hazard ratio that approached but did not quite reach statistical significance favoring the stent (hazard ratio [HR] 1.31, P=0.056).
However, an analysis of 3-year clinical events showed that the BVS was associated with both a higher rate of TVMI than the Xience (8.6% vs 5.9%, respectively; HR 1.47, P=0.03) and of TVMI related to device thrombosis (1.9% vs 0.6%; HR 1.13, P=0.02).
The risk of device thrombosis at 3 years was also threefold higher with Absorb compared with Xience, at 2.3% vs 0.7%, respectively (HR 3.12, P=0.01). In fact, all of the thrombosis events with Xience occurred within the first year following implantation and plateaued early on, whereas the thrombosis events in the BVS arm continued to climb over 3 years.
Significantly more patients in the BVS arm required revascularization (16.4% vs 12.7%, P=0.04), including ischemia-driven target vessel revascularization (11.6% vs 7.7%, P=0.01) and ischemia-driven TLR related to device thrombosis (2.2% vs 0.7%, P=0.02).
In all, 19% of patients in ABSORB III received devices in vessels that were smaller than those specified in the protocol, and these patients had generally poor outcomes, Ellis noted. In an analysis stratified by vessel size, they found that in patients with reference vessel diameters smaller than 2.25 mm, 5% of those who received the BVS had device thrombosis, compared with 1.5% of those who received the Xience. For patients with reference vessels of 2.25 mm diameter or greater, the respective rates of device thrombosis were 1.75% vs 0.5%.
Although neither comparison was statistically significant, the trends seen suggest that the use of the scaffold in small vessels is inadvisable, a finding supported by the Food and Drug Administration in an updated letter to providers issued October 31, the same day as the presentation[2].
The FDA issued the update to a previous March 18, 2017 letter to healthcare providers based on the new ABSORB III results that “continue to show an increased rate of major adverse cardiac events and BVS scaffold thrombosis in patients receiving the Absorb GT1 Bioresorbable Vascular Scaffold when compared with patients treated with the approved metallic Xience drug-eluting stent,” a statement from the agency noted.
The agency’s recommendations for healthcare providers outlined in its previous letter “remain unchanged,” the statement notes. “Although healthcare providers with available inventory may continue to implant the BVS, they should carefully consider its safety and effectiveness and only use it if they believe it is in the best interest of their patients.
“While Abbott Vascular has discontinued sales of BVS, the manufacturer will continue to monitor patients currently enrolled in the ABSORB III and ABSORB IV US clinical studies for 5 years following BVS implantation,” the FDA writes. “Patients enrolled in these studies will be followed through standard practice and care after 5 years.”
ABSORB IV
The ABSORB IV trial was an attempt to improve results with the Absorb BVS by using more rigorous PCI techniques and allowing treatment of patients who were excluded from ABSORB III but might have benefit from a BVS, such as those with troponin-positive non-ST-elevation ACS, who tend to have softer lesions, said Dr Gregg W Stone (Columbia University, New York).
In this study, patients were randomly assigned to either Absorb BVS or Xience. The patients had either stable ischemic heart disease or ACS, including troponin-positive ACS. Patients with up to three target lesions were eligible; previous ABSORB trials allowed a maximum of two target lesions.
A total of 1288 patients in the Absorb arm and 1302 in the Xience arm completed 30-day follow-up. Rates of TLF at 30 days by intention to treat, the primary end point, were 5.0% in the Absorb arm vs 3.7% in the Xience arm. The difference was 1.29%, with a one-sided 0.025 upper boundary of the confidence interval of 2.89%, just squeezing in under the noninferiority margin of 2.9%, meaning that for this end point Absorb was noninferior to Xience.
As in ABSORB III, significantly more patients in the BVS arm than in the stent arm required revascularization of any kind (1.5% vs 0.6%, P=0.03), ischemia-driven revascularization (1.4% vs 0.6%, P=0.046), and ischemia-driven target vessel revascularization and TLR (P=0.003 and 0.01, respectively).
In addition, the rate of nonperiprocedural MI was higher with Absorb (0.8% vs 0.2%, P=0.049), and there was a trend toward higher device thrombosis with the BVS, although this fell just short of statistical significance.
Compared with ABSORB III, efforts to reduce the number of very small vessels treated paid off in lower device thrombosis rates for both the BVS and the Xience, Stone noted.
“These data, which are largely consistent with those from earlier ABSORB trials, emphasize the need for advancements in device technology and standardized technique to further improve the early safety profile of BVS,” Stone said.
Avoiding Dismantling
In a briefing prior to his presentation of the data in an oral session, Ellis said that the early device thrombosis seen with the BVS may be related to the design and thickness of the struts, which is approximately double that of contemporary drug-eluting stents.
Later device thrombosis events may be related to the phenomenon known as dismantling. If the device is not well-embedded in the vessel wall, when the device begins to lose its structural integrity as it is designed to do, it can flop into the lumen, dragging tissue with it, “and that’s inherently thrombogenic,” Ellis said.
Dr Wayne Batchelor (Southern Medical Group Tallahassee, FL), who was not involved in the ABSORB trials but was an invited discussant at the briefing, told theheart.org | Medscape Cardiology that while the idea of bioresorbable stents is appealing, there’s still a long way to go.
“I think we’re going to have to see a significant design change that’s real,” he said, a thin-strutted stent that can be shown with imaging techniques to be well opposed and well implanted, avoiding any dismantling.
“In order to get the long-term outcomes, we’re going to need some kind of signal, in terms of a surrogate end point, that’s showing a positive effect,” he said.
Should that ideal stent become available, validation will require clinical trials enrolling large numbers of patients and following them for a long period of time, he told theheart.org | Medscape Cardiology.
In an editorial accompanying the ABSORB III results[3], Dr Spencer B King III (Emory University, Atlanta, GA) and Dr Bill D Gogas (Saint Joseph’s Heart and Vascular Institute, Atlanta, GA) urge that investigators continue trying to perfect BVS anyway.
“The reason to persevere is not because of any expectation that scaffolds can beat metal stents in the intermediate term but the concern that metal stents will begin to produce significant adverse events many years after implantation. That will have to become a demonstrated reality rather than a hypothetical speculation for bioresorbable scaffolds to replace metal stents. For the time being, although the ABSORBing scaffold has vanished, we believe that improved disappearing technologies will eventually reappear; whether they will be competitive with current and future coronary stents remains questionable,” they write.
The ABSORB trials are supported by Abbott Vascular. Ellis disclosed consultant and research funding in the last 12 months from Abbott Vascular, Boston Scientific, and Medtronic. Stone is chair of the ABSORB global clinical trial program (uncompensated) and a consultant to Reva. Batchelor has disclosed serving as an advisor or consultant and served on speaker’s bureaus for Abbott Laboratories and Cordis. King and Gogas reported no relevant financial relationships.
For more from theheart | Medscape Cardiology, follow us on Twitter and Facebook.
Tidak ada komentar:
Posting Komentar