Undiscovered pathology of transient scaffolding t1remains a driver of failures in clinical trials

AIM: To statistically examine the released clinical trials and meta-analyses of polymeric bioresorbable scaffolds resuming the main accomplishments in the field with a translation to the routine clinical practice. METHODS: The statistical power in clinical trials such as ABSORB Japan, ABSORB China, EVERBIO II, AIDA, and few meta-analyses by the post hoc odds ratio-based sample size calculation, and the patterns of artery remodeling published in papers from ABSORB A and B trials were evaluated. RESULTS: The phenomenal admiration from the first ABSORB studies in 2006-2013 was replaced by the tremendous disappointment in 2014-2017 due to reported relatively higher rates of target lesion failure (a mean prevalence of 9.16%) and device thrombosis (2.38%) in randomized controlled trials. Otherwise, bioresorbable vascular scaffold (BVS) performs as well as the metallic drug-eluting stent (DES) with a trend toward some benefits for cardiac mortality [risk ratio (RR), 0.58-0.94, P > 0.05]. The underpowered design was confirmed for some studies such as ABSORB Japan, ABSORB China, EVERBIO II, AIDA trials, and meta-analyses of Polimeni, Collet, and Mahmoud with some unintentional bias (judged by the asymmetrical Funnel plot). Scaffold thrombosis rates with Absorb BRS were comparable with DES performed with a so-called strategy of the BVS implantation with optimized pre-dilation (P), sizing (S) and post-dilation (P) (PSP) implantation (RR, PSP vs no PSP 0.37) achieving 0.35 per 100 patient-years, which is comparable to the RR 0.49 with bare-metal stents and the RR 1.06 with everolimus DES. Both ABSORB II and ABSORB III trials were powered enough for a five-year follow-up, but the results were not entirely conclusive due to the mostly non-significant fashion of data. The powered meta-analyses were built mostly on statistically poor findings. CONCLUSION: The misunderstanding of the pathology of transient scaffolding drives the failures of the clinical trials. More bench studies of the vascular response are required. Several next-generation BVS including multifunctional electronic scaffold grant cardiology with a huge promise to make BVS technology great again.