Author + information
- Stephen G. Ellis, MD∗ ()
- ↵∗Address for correspondence:
Dr. Stephen G. Ellis, Cleveland Clinic, Department of Cardiovascular Medicine, Desk J2-3, 9500 Euclid Avenue, Cleveland, Ohio 44195-0001.
With great excitement nearly a decade ago, a number of interventional thought and industry leaders embraced the concept of a bioresorbable scaffold (BRS) in an attempt to attenuate the truly long-term consequences of drug-eluting stent (DES) placement in coronary arteries, namely an approximately 2% per year rate of target lesion failure extending beyond year 1, perhaps forever. This late risk was attributed to the permanent presence of a metallic and often polymer “irritant,” hence the thinking that if the device went away, so would the problem. Both polymer and metallic devices were designed and tested, initially limited by inflammation and poor vessel support, but eventually evolving into devices that gained nearly world-wide regulatory approval.
However, close inspection of the results of current-generation devices has raised legitimate concerns about their propensity toward thrombosis (1). Current thinking attributes this risk in the best studied device by far, the Abbott Vascular Absorb scaffold (BVS) (Abbott Vascular, Santa Clara, California), to both the device itself and how it has been implanted (2).
There appear to be 2 phases of risk: early in small vessels and later in large vessels. Due to its sizeable strut width (2× strut size compared with metallic stents in order to match their radial strength), the scaffold acts more like a snowshoe than a cross country ski on soft snow and typically poorly “scores” and embeds into the vessel wall when implanted like a current DES. Amplifying this problem is that the scaffold also has a rectangular shape and excessive height when compared with current DES, thus protruding from the vessel wall and engendering blood flow turbulence, with the result being a 2× risk of device thrombosis versus DES during the first 6 to 12 months after implantation seen consistently in early studies. Post hoc analysis suggest that this problem can be ameliorated by high pressure and somewhat oversized balloon (1.1 to 1.25:1) post-dilation, but this needs prospective confirmation (3,4).
As the device begins to lose its structural rigidly after 6 to 12 months, the late risk phase ensues. Here, if the device has not been well apposed to the vessel wall at implantation (sometimes not so easy to tell with routine angiography), then without having been embraced by and healed into the vessel wall, it can collapse and draw endothelial and wall fragments into the lumen (“dismantling”)—another stimulus for thrombosis. Presumably, a better implantation technique will alleviate this problem, too, but the only studies for which we have long-term follow-up in sizable numbers of patients were performed before these implantation issues were understood.
Beyond this, of course, is the fact that the “value proposition” of the entire concept—that patients will see better outcomes after the device resorbs (∼3 years for the Absorb scaffold)—has really yet to be tested, because so few patients have been followed in controlled comparative studies beyond 3 years.
In this issue of JACC: Cardiovascular Interventions, we now have a report of a carefully performed study with a newer BRS, the Fantom device (REVA Medical, San Diego, California), from Cohort A of the Fantom II (Safety & Performance Study of the FANTOM Sirolimus-Eluting Bioresorbable Coronary Scaffold) study (5). This device is made from a different polymer than the Absorb BVS (a polycarbonate copolymer of tyrosine analogs vs. PLLA), has somewhat thinner but still rectangular struts (125 μm vs. 157 μm), reabsorbs over 1.5 to 2 years and elutes sirolimus instead of everolimus. Unlike some BRS, it does not require refrigeration, and unlike the Absorb BVS, it can be expanded above nominal size by 0.75 to 1.0 mm without risk of fracture. In the Fantom I study, 7 patients underwent device delivery and were followed with intravascular ultrasound and optical coherence tomography for 4 months with satisfactory results (6). The Fantom II study’s focus was principally on efficacy at 6 months as assessed by quantitative coronary angiography–determined late loss in 117 patients with relatively simple anatomy and clinical presentation (typical for early DES studies.) The rate of major adverse cardiovascular events was also evaluated, but the study really wasn’t well-powered to assess this unless the results were awful.
From this study, Abizaid et al. (5) report apparently encouraging results: using a technique characterized by relatively frequent post-dilatation (76%, with a 10% oversized balloon at a mean pressure of 16.6 atm) and nearly uniform use of intravascular imaging, in-device late loss of 0.25 ± 0.40 mm with 85% angiographic follow-up, major adverse cardiovascular events in 2.9% and scaffold thrombosis in 0.9% of patients. There were also 4 device delivery failures (3.3%).
What should we make of these results?
Sirolimus has proven to be an effective antirestenosis agent when given in an appropriate dose, so the efficacy results are as expected, but reassuring. Recall that provision of mean and SD of late loss really doesn’t tell the whole story, however, because clinical restenosis only occurs at the far “tail” of the late loss cumulative distribution curve, when late loss exceeds about 1 mm. No such curve was provided. However, the binary restenosis rate of 2% suggests this should not be a problem, at least in the type of patients studied. Regarding the failure to deliver patients, 4 of 121 sounds a bit high, but without provision of details, it’s hard to know what to conclude.
Of course, given the history of BRS before it, the real question is one of safety over time. The thinner struts than the Absorb device, fairly aggressive use of post-dilatation, frequent use of intravascular imaging and reabsorption within 2 years provides hope that the risk of device thrombosis may be acceptable. With 9-month follow-up, Cohort B will provide some information, but will hardly be definitive.
In short, these results should provide impetus for a larger and more definitive study. In the meanwhile, the 1 year ABSORB IV study results will likely either provide a death knell or new life for that device, and perhaps the long term findings from earlier ABSORB trials (II, III, Japan, and China) will tell us if the long-term value proposition of BRS remains worth pursuing.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Dr. Ellis has been a consultant for Abbott Vascular, Boston Scientific, and Medtronic; and has received research funding from Abbott Vascular and Boston Scientific.
- Colombo A.,
- Ruparelia N.
- Arroyo D.,
- Cook S.,
- Puricel S.
- Ellis S.G.,
- Gori T.,
- Steffenino G.,
- et al.
- Abizaid A.,
- Carrié D.,
- Frey N.,
- et al.
- de Ribamar Costa J.,
- Abizaid A.,
- Chamie D.,
- Lansky A.,
- Kochman J.,
- Koltowski L.