Systematic Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Oct 26, 2018; 10(10): 165-186
Published online Oct 26, 2018. doi: 10.4330/wjc.v10.i10.165
Undiscovered pathology of transient scaffolding t1remains a driver of failures in clinical trials
Alexander N Kharlamov
Alexander N Kharlamov, Department of Interventional Cardiovascular Biomedicine, De Haar Research Foundation, Amsterdam 1069CD, The Netherlands.
Alexander N Kharlamov, Research Division, Transfiguration Clinic, Yekaterinburg 620078, Russia
Author contributions: Kharlamov AN was the only author who comprehensively contributed to the analysis and writing.
Conflict-of-interest statement: The author does not have any conflict of interest to report.
Open-Access: This article is an open-access article, which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Alexander N Kharlamov, MD, Academic Research, Doctor, Lecturer, Department of Interventional Cardiovascular Biomedicine, De Haar Research Foundation, Keurenplein 41, Box G9950, 1069CD Amsterdam, The Netherlands. akharlamov@dhrfpro.com
Telephone: +31-87-7842273
Received: March 27, 2018
Peer-review started: March 28, 2018
First decision: May 2, 2018
Revised: May 21, 2018
Accepted: August 26, 2018
Article in press: August 27, 2018
Published online: October 26, 2018
Processing time: 212 Days and 19.2 Hours
ARTICLE HIGHLIGHTS
Research background

Bioresorbable vascular scaffold (BVS) initially had incredible success in the first ABSORB studies in 2006-2013, but was consequently deemed a failure due to reported relatively higher rates of target lesion failure (TLF) and device thrombosis in randomized controlled trials. However, BVS performs as well as the metallic drug-eluting stent (DES) with a trend toward some benefits for cardiac mortality.

Research motivation

The exploration of the insights in statistics of the relevant studies has a potential to discover the main obstacles of the BVS research and development preventing major cardiovascular events and therefore improving clinical outcomes adapting the technology in routine clinical practice.

Research objectives

The overarching objective was to supplant the perils of the current standard of care with the polymeric bioresorbable scaffolds.

Research methods

We evaluated the statistical power in clinical trials such as ABSORB Japan, ABSORB China, EVERBIO II, AIDA, and meta-analyses by the post hoc OR-based sample size calculation, and the patterns of artery remodeling published in papers from ABSORB A and B trials.

Research results

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). ST rates with Absorb BRS were comparable with DES performed with a strategy of the BVS implantation with optimized pre-dilation (P), sizing (S), and post-dilation (P) (PSP) implantation 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.

Research conclusions

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.

Research perspectives

The biology of transient scaffolding remains mostly unknown. The thin-strut scaffolds and stents with advanced mechanical features are able to partly solve the problem of device thrombosis. Nevertheless, the unclear mechanism of related complications challenges the further development of the technology. Future research must be focused on both bench and bedside studies of vascular biology and pathology of the transient scaffolding in order to understand which mechanism is a leading source of the troubles that we face in routine clinical practice with bioresorbable scaffolds.