Author + information
- Manrique Alvarez, MD and
- Robert J. Applegate, MD∗ ()
- ↵∗Address for correspondence:
Dr. Robert J. Applegate, Section of Cardiovascular Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157-1045.
Over the past decade a fully bioresorbable vascular scaffold (BVS) has gone from bench top to implantation in patients, and has been one of the most extensively studied intra coronary devices ever introduced into clinical practice. The landmark, ABSORB III (A Clinical Evaluation of Absorb BVS, the Everolimus-eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects with de Novo Native Coronary Artery Lesions) trial, comparing BVS to everolimus-eluting cobalt chromium stent (EES), by Ellis et al. (1) led to the U.S. Food and Drug Administration’s approval of the first fully absorbable stent, the Absorb GT1 BVS by Abbott Vascular, in the United States in 2016. However, clinical uptake of BVS in the United States has been slow due to several factors. First, BVS was approved at a time when stent technology and design had matured considerably from the first-generation thick-strutted, stainless steel stents to thinner, more flexible stents with improved polymer and drug delivery, setting a high standard for new device development. Second, concerns of an increase in BVS stent thrombosis emerged recently damping enthusiasm for its use.
Recent observational studies have raised concerns of an increased incidence of BVS thrombosis (scaffold thrombosis [ScT]), a serious and frequently life-threatening complication of percutaneous coronary intervention, when compared with stent thrombosis rates of current generation DES. Capodanno et al. (2) published real-world outcomes from the GHOST-EU (Gauging coronary Healing with BiOresorbable Scaffolding platforms in Europe) registry on nearly 1,200 patients implanted with 1 or more BVS. They showed a cumulative incidence of definite or probable ScT of 1.5% and 2.1% at 30-day and 6-month follow-up, respectively. Similarly, Kraak et al. (3) found a 3.0% rate of definite ScT at 6 months in 135 patients in the AMC Single Centre Real World Percutaneous Coronary Intervention Registry. The AIDA (Amsterdam Investigator-initiated Absorb Strategy All-comers) randomized trial was stopped early amidst safety concerns of an increased rate of ScT compared with metallic EES (4). Finally, observations of an increase in target vessel failure of BVS compared with EES were revealed in the 2-year outcomes of the ABSORB III trial (5), resulting in a Food and Drug Administration safety alert about BVS.
In addition to these studies, a number of randomized clinical trials have also demonstrated increased rates of ScT when comparing ABSORB to EES metallic stents (Xience, Abbott Vascular; or Promus, Boston Scientific). Sorrentino et al. (6) recently published a meta-analysis of seven randomized trials (ABSORB China, ABSORB II, ABSORB III, ABSORB Japan, AIDA [Amsterdam Investigator-initiateD Absorb strategy all-comers], EVERBIO II [Everolimus-Eluting Bioresorbable Scaffolds vs. Everolimus-Eluting and Biolimus-Eluting Stents in CAD Patients], TROFI II [Everolimus-eluting bioresorbable stent vs durable polymer everolimus-eluting metallic stent in patients with ST-segment elevation myocardial infarction]) comparing BVS to EES that included almost 5,600 patients. They found a statistically significant increase in definite or probable ScT, 2.4% versus 0.7% stent thrombosis (p < 0.0001). In addition, the risk of ScT over time was concordant across early (p = 0.04), late (p = 0.07), and very late (p = 0.006) intervals. These findings have stimulated intense interest into the cause of the disproportionate device thrombosis rates between BVS and drug-eluting stents (DES).
The exact mechanism of ScT has not been clearly elucidated although there are likely multiple factors associated. In a recent editorial by Yamajii et al. (7), accompanying the publication of the study by Tanaka et al. (8), they identified at least 3 factors that may influence BVS failure and scaffold thrombosis: the device, the operator (i.e., the procedure and technique), and the lesion (i.e. vessel characteristics, especially the extent of calcification). In addition, several clinical and procedural factors including small vessel size (<2.5 mm), long lesion length, ostial or calcified lesions, minimal lumen diameter post-implantation, malapposition, scaffold thickness, interruption of dual antiplatelet therapy, and reduced left ventricular ejection fraction have been implicated in ScT. Not surprisingly, given the strut thickness of BVS, comparable to first-generation DES (and much thicker than contemporary metallic DES strut thickness), attention has focused on device-specific characteristics leading to incomplete expansion and possible malapposition of BVS as a potential cause of an increase in the rate of ScT, particularly in smaller-caliber vessels. Indeed, incomplete BVS expansion was observed in an imaging-based study of BVS thrombosis (9).
Observational studies by Puricel et al. (10) and Tanaka et al. (8) provided support for the concept of scaffold-vessel mismatch with inadequate stent expansion as a cause of ScT, observing lower rates of scaffold failure and ScT when an optimal implantation strategy focusing on appropriate vessel and BVS sizing and scaffold expansion was used. Nonetheless, the study by Tanaka et al. (8) also raised concerns that an optimal implantation technique may not fully adjust for device failure and ScT as the target lesion failure rate of 6.6% at 1 year in their study using an optimized implantation strategy was still significantly higher than what would have been anticipated for contemporary DES. It is noteworthy that an optimized implantation strategy for BVS was not recommended in the vast majority of patients treated in the randomized trials cited by Sorrentino et al. (6) for initial fears that there would be disruption of the polymeric struts of the BVS if an aggressive post-dilation was performed.
Despite recognition that implantation technique plays a role in ScT, more precise understanding of the interaction of vessel and BVS size and expansion on ScT is lacking. In this issue of JACC: Cardiovascular Interventions, Gori et al. (11) evaluated the timing, incidence, and quantitative coronary angiographic (QCA) findings in 657 consecutive patients treated with BVS between May 2012 and January 2015 in a single-center registry. Twenty-five definite, 2 probable, and 1 possible ScT were identified with incidence of 2.2%, 3.0%, and 4.7% at 30 days, 12 months, and 3 years, respectively. STEMI was the most common presentation of ScT in both early (n = 10) and late (n = 6) groups. Early ScT occurred while the vast majority of patients were on dual antiplatelet therapy, in contrast to only 4 of 14 in the late or very late ScT group.
Gori et al. (11) stratified patients into the “optimal implantation technique” group using patient-level analysis, whereas previous reports did so based on timing of treated patients (before vs. after optimal implantation recommendations were implemented). Key QCA parameters included minimal lumen diameter; reference vessel diameter (RVD); ratio of BVS nominal size and RVD (marker of BVS sizing); residual stenosis; MLD and RVD ratio (marker of vessel expansion); and MLD or nominal, footprint, and scaled residual stenosis (markers of device expansion). Use of an optimal implantation technique was found to be associated with a remarkably lower incidence of ScT in the early and late groups, 3.7% to 0.7% and 4.4% to 0.6%, respectively. Use of an optimal implantation technique was the only independent predictor of early ScT, whereas estimated glomerular filtration rate, treatment of right coronary artery, prior intervention, and BVS length were multivariable predictors of late or very late ScT. QCA revealed that in vessels <2.5 mm and in cases in which a >15% oversized BVS was chosen and incompletely expanded there was a strong association with early ScT. Additionally, in vessels >3.5 mm and in cases in which >15% under sizing of BVS was identified there was an increased risk of late or very late ScT.
What can we learn from this study? There are limitations of this study that should be noted. This study was done retrospectively, with all of the caveats of this type of study: possible selection biases, small cohort sizes among the different BVS sizes, an incomplete description of lesion characteristics such as the extent of calcification, and the absence of information on the potential independent impact of different lesion preparation strategies on the risk of ScT. Moreover, intracoronary imaging was not performed so information concerning scaffold malapposition can only be surmised from their results. However, the findings of Gori et al. (11) support the concept that size matters, with an interaction between vessel size, scaffold size, and appropriate scaffold expansion on the risk of ScT. For the interventionalist choosing to implant BVS, these observations strengthen the importance of using an optimal implantation technique. It is interesting to speculate whether even more aggressive scaffold expansion can ameliorate or even mitigate the relationship of BVS and vessel sizing and its effect on ScT. However, there are physical limits to which the current generation scaffold can be dilated, making very aggressive scaffold expansion problematic. Finally, to the extent that device failure arising during resorption such as scaffold discontinuity plays a role in ScT then an optimal implantation technique will not likely mitigate this type of event.
BVS are one of the latest iterations in stent technology and design. This device continues to be appealing in that it leaves “no metal behind,” with the hope of avoiding long-term device failure, or barriers to surgical revascularization. It is clear, however, that the current first-generation BVS have limitations dictated by the thickness of the polymeric struts that can result in increased rates of ScT compared with metallic DES unless an optimal implantation technique is meticulously followed. Hopefully, and similar to the development history of metallic stents, the fully bioresorbable technology will continue to develop allowing the promise of “no metal left behind” to be realized safely and effectively.
↵∗ 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. Alvarez has reported that he has no relationships relevant to the contents of this paper to disclose. Dr. Applegate has served as a consultant for Abbott Vascular.
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