By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SYNOPSIS: In the longest-term randomized, controlled study of coronary bioresorbable vascular scaffolds to date, the Absorb bioresorbable vascular scaffold was outperformed by its metallic drug-eluting stent counterpart.
SOURCE: Serruys PW, Chevalier B, Sotomi Y, et al. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): A 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet 2016;388:2479-2491.
In the world of coronary revascularization, the intuitive appeal of a bioresorbable vascular scaffold (BVS), a device that helps open a vessel but then disappears over time, is hard to overstate. The first generation of such devices is represented by Abbott Vascular’s everolimus-eluting poly(L-lactide) scaffold known as Absorb, which was approved in Europe in December 2010 but did not gain FDA approval until July 2016. Early data with this device are encouraging, but mixed, with an increase in adverse events. Because the real advantage of such devices is expected years down the road, after scaffold resorption, longer-term data have been eagerly anticipated.
Enter the three-year publication of data from the ABSORB II trial, a randomized comparison of the Absorb resorbable scaffold with the everolimus-eluting Xience metallic drug-eluting stent (DES). In this trial, 501 patients were randomized 2:1 to treatment of their coronary lesions with the Absorb or Xience devices. The trial was designed to play to the reputed strengths of the bioresorbable scaffold, with a primary endpoint of superiority of Absorb in terms of vasomotor reactivity as assessed at planned invasive angiography at three years. The co-primary endpoint was non-inferiority of angiographic late lumen loss. The trial design presumed that the Absorb vessels, after disappearance of the scaffold, would exhibit similar lumen gain but better vessel mechanics compared to those with the permanent metallic Xience stent.
The designers missed on both counts. Vasomotor reactivity was not statistically different between groups at three years, in large part because the metallic stent vessels performed better than expected. Late lumen loss was greater in the Absorb group compared with Xience (0.37 mm vs. 0.25 mm, giving a P non-inferiority of 0.78). Three-year measures of minimal lumen diameter, percentage stenosis, and in-device primary restenosis favored Xience, and all met statistical significance. Similarly, measurements by intravascular ultrasound showed a higher minimal lumen area in the Xience group as compared with Absorb (5.38 mm² vs. 4.32 mm²; P < 0.0001). Assessments of angina and the results of planned exercise stress testing were not different between the groups.
Although the trial was not powered for clinical endpoints, it nevertheless reported a two-fold increase in device-oriented clinical events with Absorb as compared with Xience (10% vs. 5%; P = 0.04), driven primarily by target-vessel myocardial infarction (MI). Of particular concern: At the three-year mark, there were eight definite scaffold thrombosis events in the Absorb group, of which six were “very late” — more than one year after deployment. By contrast, MIs in the Xience group were peri-procedural exclusively (these also were statistically greater among Absorb patients), with no definite or probable stent thrombosis events (P = 0.03 for scaffold/stent thrombosis) out to three years.
The authors concluded that the Absorb scaffold did not meet its co-primary endpoint of superior vasomotor reactivity and non-inferior late luminal loss at three years compared to a metallic stent with the same anti-restenotic drug. Investigators highlighted the need for future studies to examine aspects of optimal implantation technique, including the use of intravascular imaging.
At first glance, this trial appears to reflect very negatively on the Absorb bioresorbable vascular scaffold. Indeed, in this trial of relatively non-complex coronary lesions, the three-year measures of vasomotion and late lumen loss — exactly where a bioresorbable scaffold might be expected to shine — came out in favor of the metallic DES. In addition, although the number of patients and events were small, this trial echoed the results of several prior studies that have suggested an increase in scaffold thrombosis compared to conventional stents. Worse, the majority of these events were very late, past 12 months where one might expect the resorbable scaffold to demonstrate an advantage.
Although these data may serve to temper what might otherwise be unbridled enthusiasm for this technology, the conclusions are not all one-sided. One perspective applied by the authors is that the trial was performed early in the experience with this scaffold, between late 2011 and mid-2013, and that implantation technique was suboptimal. Indeed, the recent U.S. debut of the device has stressed meticulous implantation measures that are not uniformly performed with metallic stents and were not followed in this trial — vessel preparation with pre-dilatation sized 1:1 to the vessel, using intravascular imaging and high-pressure, post-dilatation oversized relative to the vessel. This is not just spin — available data suggest that the bioresorbable scaffold simply does not result in the same lumen gain as metallic stents when such meticulous preparation is not followed. Indeed, in ABSORB II, the lumen gain from the initial procedure was significantly less in the Absorb group as compared to Xience, and this was a major contributor to the lumen difference at three years. Following updated implantation recommendations could yield a different and more positive result for BVS. Whether the added time and expense of optimal implantation techniques are worthwhile for a majority of patients — when a less resource-intensive approach yields excellent results with metallic stents — is an open question. Even with the apparently suboptimal technique used in this trial, results with the BVS were overall very good, and event rates were reassuringly low.
An important and often-forgotten part of the equation here is duration of dual antiplatelet therapy (DAPT). With metallic stents, the safety of shorter and shorter DAPT duration has been the clear trend. Current U.S. and ESC guidelines recommend six months of DAPT after elective PCI with metallic stents, and multiple studies have suggested safety of three months or even less. The thicker struts of the Absorb scaffold, along with other factors, leads most experts to suggest that the optimal duration of DAPT with this technology is significantly longer than with metallic stents. This area will require further study, but for now many are recommending a full year or even more of DAPT post-implant for the Absorb.
For now, the Absorb BVS has its best available data in younger patients with non-complex disease in vessels larger than 2.5 mm. Whether the long-term promise of this technology will be realized with current or future iterations of the device, in concert with greater experience with patient and lesion selection and implantation technique, remains to be seen.