A review of bioresorbable scaffolds: hype or hope?

INTRODUCTION

Bioresorbable scaffolds (BRSs) are considered a major advance in the field of percutaneous coronary intervention.(1) They are designed to overcome the drawbacks of metallic drug-eluting stents (DESs), which include chronic local inflammatory reaction, absence of physiological coronary vasomotion, late stent thrombosis and the prevention of future coronary artery bypass surgery at the same site.(2-5) The Absorb Bioresorbable Vascular Scaffold (BVS; Abbott Vascular, Santa Clara, CA, USA), one of the most extensively evaluated BRSs, has been subjected to numerous studies. This review will critically analyse the potential safety, efficacy and complications of BRSs.

POTENTIAL BENEFITS OF BIORESORBABLE SCAFFOLDS

The BRS system works in three phases to achieve vascular reparative therapy: revascularisation, restoration and resorption. In the revascularisation phase, the BRS is intended to mimic the characteristics of the metallic DES (i.e. scaffold deployment with minimum recoil, provision of high radial strength and controlled release of an antiproliferative drug). Subsequently, in the restoration phase, vasomotion of the vessel is re-established, and there is a transition from active to more passive support. The resorption phase is characterised by the degradation and metabolism of the scaffold.(6)

The BRS offers unique advantages that are not found in a metallic DES: (a) The restoration of coronary vasomotion is one of the main benefits. The BRS allows recovery of the endothelial function and a significant increase in the luminal diameter of the scaffold segment in response to vasoactive agents.(7) The vessel recovers the ability to respond to physiological stimuli, which may translate into reduced anginal episodes and a better functional capacity than when the metallic DES is used. (b) In contrast to the metallic DES, the BRS has the potential for late lumen enlargement, starting at the resorption phase. Multimodality imaging has documented late lumen enlargement among patients in the ABSORB Cohort A and Cohort B trials.(7-9) (c) Following the resorption phase, BRS struts are replaced by neointima, which resembles the thick fibrous cap of a de novo atherosclerotic lesion.(10,11) The BRS may offer security in terms of stabilisation of a vulnerable plaque and possibly also prevent acute coronary syndrome, although further studies are necessary to determine whether this potential effect can be achieved. (d) After complete resorption, no foreign body is left in the vessel. Hence, the risks of very late stent thrombosis are potentially eliminated. (e) The BRS is relatively more transparent than the metallic DES and facilitates serial noninvasive imaging (coronary computed tomography and magnetic resonance imaging). (f) In patients needing repeat revascularisation, the BRS may permit surgeons to carry out an anastomosis of bypass grafts at distal segments.

USE IN CLINICAL PRACTICE

The first BRS used in humans was the Igaki-Tamai stent (Kyoto Medical Planning Co Ltd, Kyoto, Japan).(12) Made from poly-L-lactide monofilament, the Igaki-Tamai stent is a coil stent that has a zigzag helical design and is self-expandable when heated. The stent struts disappear within three years. Immediate and six-month results suggested the safety and efficacy of the novel Igaki-Tamai stent.(12) Its main drawbacks are the need for an 8-French guiding catheter for stent delivery, the absence of antiproliferative drug elution, and the use of a heated contrast dye that may result in vessel wall injury. Further research and development of this stent was interrupted by the evolution of the DES. However, the long-term clinical outcomes of the Igaki-Tamai stent are reassuring(13) and lay the foundation for studies on various BRSs.

The most extensively studied BRS to date is the BVS. It is composed of a balloon-expandable poly-L-lactide scaffold (150-µm thick), which degrades completely in 2–3 years, and a thin, bioabsorbable poly-D, L-lactide coating for controlled release of everolimus. Radiopaque platinum markers at each end of the scaffold enable clear visualisation on imaging. The BVS was first evaluated in the ABSORB clinical trials (Cohorts A and B) and showed encouraging results.(14,15) Subsequently, a number of single-arm studies and a few randomised controlled studies were published.

The other BRS that has been evaluated in clinical studies is the DESolve® Scaffold (Elixir Medical Corporation, Sunnyvale, CA, USA).(16) Similar to the BVS, it is composed of a poly-L-lactide scaffold and elutes either antiproliferative myolimus (first-generation) or novolimus (second-generation). In comparison to other BRSs, the DESolve Scaffold is believed to have a wider range of expansion, with reduced risk of strut fracture and self-correction of minor malapposition.

CURRENT SUPPORTIVE EVIDENCE

The vast majority of data that supports the use of the BRS in humans comes from studies using the BVS. The first-generation BVS (BVS 1.0) was tested in a series of 30 patients from the ABSORB Cohort A study.(14) Although the cohort demonstrated encouraging long-term outcomes,(7,17) the first-generation BVS demonstrated a slightly higher rate of acute and late recoil.(18,19) To overcome this limitation, the strut design and the polymer’s manufacturing process was modified in the revised version (BVS 1.1). This was tested in 101 patients from the ABSORB Cohort B study. Alteration of the scaffold design led to a significant improvement in the immediate and medium-term outcomes of this novel second-generation BVS.(15) This paved the way for the conduct of a randomised controlled trial comparing the BVS with the metallic DES. A five-year follow-up study on the same cohort of patients (i.e. Cohort B) yielded low rates of restenosis and major adverse cardiac events.(20) To date, there have been six randomised trials that compared the BVS with the DES. The various studies are illustrated in Table I.

Table I

Randomised trials of the Absorb Bioresorbable Vascular Scaffold (BVS).

ABSORB II was the first randomised controlled trial comparing the Absorb BVS with the XIENCE V cobalt-chromium everolimus-eluting stent (CoCr-EES; Boston Scientific, Marlborough, MA, USA). The co-primary endpoints of this study were the assessment of vasomotion at three years and the difference between the minimum lumen diameter after the index procedure and at three years. In the interim one-year analysis, the Absorb BVS showed a similar clinical outcome as the CoCr-EES.(21) However, the study was not adequately powered for clinical endpoints. The two-year follow-up data from this trial was reported at the Transcatheter Cardiovascular Therapeutics 2015 conference. Although the patient-oriented composite endpoint did not differ between the two groups, target lesion failure (a composite of cardiac death, target-vessel myocardial infarction and clinically indicated target-lesion revascularisation) was significantly higher in the BVS group (BVS 7.0% vs. CoCr-EES 3.0%; p = 0.07).

ABSORB III(22) evaluated the relative safety and efficacy of the Absorb BVS versus the CoCr-EES in patients with coronary artery disease. The primary endpoint was target lesion failure (a composite of cardiac death, target-vessel myocardial infarction or ischaemia-driven target-lesion revascularisation) at one year. Target lesion failure occurred in 7.8% of patients in the Absorb group and 6.1% of patients in the CoCr-EES group (p = 0.007 for non-inferiority; p = 0.16 for superiority).(22) Despite the performance of the Absorb BVS being comparable to that of the CoCr-EES, there were some concerns. The overall device thrombosis rate was reported to be higher in the Absorb group than in the CoCr-EES group (1.5% vs. 0.7%), although the difference was not significant. In comparison to the CoCr-EES group, the rate of subacute device thrombosis was significantly greater in the Absorb group.(22) One of the important limitations of the ABSORB III study was its inability to examine low-frequency events such as cardiac death and device thrombosis. Clinical follow-up in this trial will be performed for five years and the results are awaited.

An overview of all trials on BVS showed no significant difference in one-year outcomes between the BVS and CoCr-EES for most endpoints. A pooled meta-analysis of four randomised trials showed similar results for both the BVS and CoCr-EES in patient- and device-oriented composite endpoints at one year.(27) The BVS was developed to circumvent the limitations of the metallic DES, which are evident after one year of implantation. Imaging evidence supports the novel attributes of the BVS,(7,8) but improved late clinical outcomes are required to definitively show the superior benefit of the BVS, as compared to the metallic DES. Hence, the results are not expected to become obvious until 3–5 years after implantation, and there is a need to wait for the clinical outcomes of ongoing large-scale randomised trials (e.g. ABSORB IV).

Data from multiple single-arm trials have provided reassurance of the safety and efficacy of the BVS. Interim analysis of the ABSORB EXTEND study revealed low rates of major adverse cardiac events and scaffold thrombosis at one year.(28) Although the majority of studies on the BVS have been on stable patients and simple lesions, with better understanding of the BVS and improved operator expertise, it is now being used in complex lesion subsets. There is data on the application of the BVS in acute coronary syndrome,(21,26,28,29) bifurcation lesions,(30,31) left main disease,(32,33) chronic total occlusion,(34) calcific lesions,(35) in-stent restenosis(36) and multi-vessel disease.(37)

IMPLANTATION TECHNIQUE

The design and properties of the BVS are different from that of the metallic DES. Hence, appropriate technique for BVS implantation is vital for procedural success and clinical outcomes. A consensus has been reached on the optimal implantation procedure, and the key points are listed as follows.(38,39)

DRAWBACKS AND CONCERNS

The drawbacks of the BRS are related to the mechanical properties of the scaffold structure and the technique of stent implantation. The higher strut thickness limits deliverability and increases non-laminar flow, and the higher crossing profile restricts its use in difficult anatomical settings. The strut thickness of the BRS may result in more frequent side-branch occlusions and contribute to periprocedural myocardial infarction.(40) Early causes of BRS failure include scaffold dislodgement, acute recoil and scaffold thrombosis. Scaffold dislodgement has principally been reported in lesions that are not adequately predilated and on the second insertion of the same scaffold.(41) Early scaffold thrombosis reported in the GHOST-EU registry(37) suggests that there is scope for improvement in terms of lesion selection and optimisation of BRS implantation. Acute recoil of the BRS is another important drawback related to improper stent implantation technique.(42)

Very late stent thrombosis events are not expected in view of complete resorption of the BRS. However, such events have been documented in the literature and may indicate delayed healing, with the need to continue dual antiplatelet therapy beyond the first year.(43) There is no convincing data or evidence in favour of shortening the duration of dual antiplatelet therapy in BRS-implanted individuals. Neoatherosclerosis, scaffold restenosis and acquired coronary aneurysm are the other late causes of BRS failure.(44,45)

CONCLUSION

The concept of the BRS is logical and attractive. The short- and medium-term results are encouraging, but its long-term safety remains unknown. Therefore, more randomised long-term clinical data will be required to determine whether the theoretical advantage of the BRS can translate into routine practice. The superiority of the BRS over the second-generation DES has not been proven. Use of the BRS can be considered in a carefully selected group of individuals (e.g. young patients, lesions without significant calcification and tortuosity, long lesions, multi-vessel disease and lesions with spontaneous coronary artery dissection), with strict adherence to an optimal implantation technique.