The Pitfalls and Challenges
Most of the existing literature on BRS is limited to their utility in simple Type A lesions. The interventionalists thus remain skeptical regarding their applicability in complex lesions more commonly encountered in real world practice. The delivery of BRS in calcified and complex lesions is relatively difficult given the stent size and strut thickness. A recent study reported higher strut malapposition with BRS used in fibrocalcific plaques.43 Additionally, the relatively lower radial strength of BRS could plausibly limit their expansion in heavily calcified lesions. Given the high profile of these scaffolds, adequate lesion preparation with rotablation or noncompliant scoring balloons might be obligatory to expand their use in complex lesions per some authors.44 Indeed, the limited expansion of BRS precludes aggressive post-dilation, which makes adequate lesion preparation and vessel sizing imperative. Improved BRS expansion has been previously noted following 1:1 balloon:vessel pre-dilation.43 The restricted distensibility of everolimus-eluting BRS may require IVUS, OCT or quantitative coronary angiography (QCA) for precise measurement of maximal distal and proximal coronary luminal reference diameters (Dmax) to accurately size the stent and thus avoid over or undersizing of the device with subsequent incomplete strut apposition.24,45
The chronic scaffold recoil noted with ABSORB Version 1.0 in Cohort A trial occurs secondary to loss of radial strength during resorption and is not observed with non-absorbable DES. Likewise, the in-vivo resorption of the scaffold and its mechanical strength do not have a linear relationship.38 This might make the decline in device’s mechanical performance with minimal resorption or changes in stent mass unpredictable. Conversely, the DREAMS magnesium based scaffold showed better conformability with superior strut apposition in the BIOSOLVE-I trial though with other limitations noted above.42 The other notable limitation of polymer (PLLA) based BRS is the lack of radio-opacity, which obligates the use of radiopaque markers.
Special Populations and Future Directions
Besides long calcified lesions, data is also sparse for use of BRS in treatment of in-stent restenosis (ISR). The BRS might prove attractive for ISR and avoid multiple metallic layers of scaffolds and polymers in a coronary artery thereby plausibly reducing chronic inflammation and neointimal hyperplasia.46 Likewise, clinical studies have neither included bifurcation lesions with side branches ≥ 2 mm in diameter, evaluated the “kissing balloon” technique nor is there sufficient data to recommend the use of BRS in chronic total occlusions or coronary artery bypass grafts.24
Furthermore, BRS will need critical analysis in various higher risk subgroups including diabetics, elderly as well as individuals presenting with ACS in larger sample size studies with longer prospective followups. In a propensity match analysis of ABSORB BRS (from Cohort B and Extend Trials) and everolimus DES (from SPIRIT trials), no significant difference in outcomes was noted amongst diabetic patients treated with either platform.47
The pace of scaffold resorption can vary depending on the PLLA manufacturing process. Thus, every device needs to be tested appropriately for in-vivo biocompatibility. This is important since previously published literature has demonstrated the influence of scaffold’s molecular weight on the degree of inflammation,48 which could further influence the neointimal response. Additionally, with varying absorption times, the ideal resorption duration of scaffolding remains to be elucidated. On the basis of previously published IVUS study that showed negative vascular remodelling for up to six months8 an ideal scaffold should provide protection against negative remodelling for at least six months though this merits further confirmation.
The current generation of DES has demonstrated improved outcomes with especially reduced rates of both late and very late ST.49 Indeed, emerging literature involving recent post-hoc analysis of pooled data from major trials demonstrated no adverse thrombotic events after earlier discontinuation of DAPT. This poses several questions for emerging technology as BRS including feasibility of designing adequately powered trials to prove the superiority of BRS over currently available DES.50 Whether BRS would further reduce DAPT requirements, lower stent fracture complications and even improve coronary vasomotor function over long term remains to be demonstrated in larger clinical and in-vivo physiological studies. Future pre-clinical studies focused on extensively studying pathophysiological underpinnings of BRS mechanisms are imperative. Furthermore, the real clinical implications of vasomotor restoration phenomenon would need further evaluation.
Of note, the various physiological benefits of BRS are not expected until late (likely after first year) and thus longer follow-ups would be needed to elucidate favourable contributions over their metallic counterparts. Indeed, in a recent serial tomographic evaluation of BRS form ABSORB Cohort B, the in-scaffold loss was noted to be stable after one year in contradistinction to everolimus stent from SPIRIT II trial (increase from 0.17 mm at six months to 0.33 mm at years years).51,52 This was accompanied by significant luminal enlargement between one and three years (6.35 mm2 at one year and 6.81 mm2 at three years, p < 0.001) in case of BRS.16