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Biodegradable Stent Case Study Regulations

Boston Scientific (NYSE:BSX) is looking to terminate its Renuvia bioresorbable coronary stent program, according to a Minneapolis Star Tribune report.

The move comes after new clinical studies of Abbott‘s (NYSE:ABT) Absorb bioresorbable stent indicated that use of the device resulted in a higher risk of serious adverse events compared to metal stents.

Marlborough, Mass.-based Boston Scientific said that while the bioabsorbable plastic stents do “show promise”, the company will be focusing on different areas of development.

“We’ve just decided strategically that there are bigger problems to deal with, and more socially impactful problems, like stroke, like heart failure, that need our attention. And it is better to invest in those things that will have bigger impacts than to try and overcome the technical challenges [of bioresorbable stents] in the short term,” global chief medical officer Dr. Ian Meredith told the Star Tribune.

So far, Abbott is the only medical device company in the US to have won approval for a completely bioresorbable stent with its Absorb GTI BVS device.

While the market for such stents was expected to reach the billions by 2021, data on heightened adverse events associated with the Absorb stent have damaged those prospects. A study released this month backed up earlier data, released in March, which showed increased rates of adverse events at 2-years with the Absorb when compared against metallic drug-eluting stents.

“The current findings … provide evidence beyond any reasonable doubt that Absorb BVS is inferior to new-generation [metal stents made by Abbott] on both efficacy and safety throughout 2 years. It cannot be anticipated that the potential long-term benefits of the current version of Absorb BVS will offset the excess in adverse events reported during the first 2 years,” wrote authors of a Lancet comment piece published earlier this month, according to the Star Tribune.

Data from the recent study, also published in Lancet this month, reported that while mortality rates were similar between Absorb and metal-stent patients, those treated with the Absorb showed statistically significantly higher rates of blood vessel blockage and subsequent heart attacks.

Boston Scientific is still set to release 6-month results from a trial of its Renuvia at the Transcatheter Cardiovascular Therapeutics meeting later this year, and while data looks solid, the company is still planning on cutting support for the program, according to the report.

“You have to ask the question, do we actually put the effort into studying this in much more complex patients, many of whom are at higher risk of events anyway, against a background of literature from all over the world showing consistently that this strategy is associated with worse outcomes? We think it doesn’t make sense to do this, and … we should put our energies into treating bigger problems affecting the human race in the 21st century,” Meredith told the Star Tribune.

Filed Under: Business/Financial News, Cardiovascular, Research & Development, Stents, VascularTagged With: Abbott, Boston Scientific

Abstract

Background

The aim of this study was to compare the safety and efficacy of biodegradable-polymer (BP) drug-eluting stents (DES), bare metal stents (BMS), and durable-polymer DES in patients undergoing coronary revascularization, we performed a systematic review and network meta-analysis using a Bayesian framework.

Methods and results

Study stents included BMS, paclitaxel-eluting (PES), sirolimus-eluting (SES), endeavor zotarolimus-eluting (ZES-E), cobalt–chromium everolimus-eluting (CoCr-EES), platinium–chromium everolimus-eluting (PtCr-EES), resolute zotarolimus-eluting (ZES-R), and BP biolimus-eluting stents (BP-BES). After a systematic electronic search, 113 trials with 90 584 patients were selected. The principal endpoint was definite or probable stent thrombosis (ST) defined according to the Academic Research Consortium within 1 year.

Results

Biodegradable polymer-biolimus-eluting stents [OR, 0.56; 95% credible interval (CrI), 0.33–0.90], SES (OR, 0.53; 95% CrI, 0.38–0.73), CoCr-EES (OR, 0.34; 95% CrI, 0.23–0.52), and PtCr-EES (OR, 0.31; 95% CrI, 0.10–0.90) were all superior to BMS in terms of definite or probable ST within 1 year. Cobalt–chromium everolimus-eluting stents demonstrated the lowest risk of ST of all stents at all times after stent implantation. Biodegradable polymer-biolimus-eluting stents was associated with a higher risk of definite or probable ST than CoCr-EES (OR, 1.72; 95% CrI, 1.04–2.98). All DES reduced the need for repeat revascularization, and all but PES reduced the risk of myocardial infarction compared with BMS.

Conclusions

All DESs but PES and ZES-E were superior to BMS in terms of ST within 1 year. Cobalt–chromium everolimus-eluting stents was safer than any DES even including BP-BES. Our results suggest that not only the biodegradability of polymer, but the optimal combination of stent alloy, design, strut thickness, polymer, and drug all combined determine the safety of DES.

Bare metal stents, Drug-eluting stents, Biodegradable polymer drug-eluting stents, Meta-analysis

See page 1098 for the editorial comment on this article (doi:10.1093/eurheartj/ehu037)

Introduction

Drug-eluting stents (DESs) compared with bare metal stents (BMS) have reduced the need for repeat revascularization,1–3 and have largely replaced BMS in the treatment of coronary artery disease. However, concerns have been raised regarding the potential for late stent thrombosis (ST) with DES related to delayed healing of vessel wall.4,5 Studies have suggested that a reaction to the durable polymer (DP) containing the drug may trigger continued inflammation and late ST.6–8 Therefore, developments in newer generation of DES have been focused on biocompatible polymer, biodegradable-polymer (BP) DESs, and polymer-free DESs.

Recent meta-analyses have shown improved safety as well as efficacy of newer-generation DESs.9–11 However, the major limitations of the previous meta-analyses were that the proportion of patients with newer-generation DES were relatively small and thus comparisons had restricted statistical power. Furthermore, BP-DESs were not included in the analyses. Although BP-DESs have yet to receive approval in the USA, they are widely used across the world including Asia and Europe. In this study, we compared clinical outcomes of various types of coronary stents to assess their safety and efficacy. Specifically, we analysed (i) whether DES increases or decreases the risk of ST compared with BMSs, (ii) whether different DP-DESs are vulnerable to ST in the long-term clinical follow-up, (iii) the safety and efficacy of newer-generation DP-DESs and BP-DESs compared against each other and against BMS. A systematic literature review of randomized controlled trials (RCTs) comparing coronary stents was performed, and the data from the review were the basis of a multiple-treatments network meta-analysis using a Bayesian framework.12

Methods

Eligibility criteria

We included RCTs comparing two or more coronary stents in patients undergoing percutaneous coronary intervention. Study stents were restricted to those approved by regulatory bodies of both Korea (Ministry of Food and Drug Safety) and Europe (CE mark) and included the following stent types: (i) BMS, (ii) paclitaxel-eluting stents (PESs, Boston Scientific), (iii) sirolimus-eluting stent (SES, Cordis), (iv) endeavor zotarolimus-eluting stents (ZES-E, Medtronic), (v) cobalt–chromium everolimus-eluting stents (CoCr-EES, Abbott Vascular and Boston Scientific), (vi) platinum–chromium everolimus-eluting stents (PtCr-EES, Boston Scientific), (vii) resolute zotarolimus-eluting stents (ZES-R, Medtronic), (viii) BP biolimus A9-eluting stents (BP-BES, Biosensors and Terumo), and (ix) BP everolimus-eluting stents (BP-EES, Boston Scientific). After the initial analysis, the protocol was amended to exclude BP-EES from the study, because the sample size and the event numbers in the only study that tested BP-EESs were very small.13 We excluded studies (i) comparing two stents with different stent design within the same category described above,14 (ii) in which specific type of DESs was not pre-defined and the choice among available DES was left to the investigators' discretion (for example, BMSs vs. any DESs),15,16 and (iii) published in a language other than English.17 No restrictions were imposed on study period, sample size, or publication status as well as patient or lesion criteria. Thus, studies with exclusive enrollment of patients with acute myocardial infarction (MI) or with bypass grafts were also included in the meta-analysis.

Data sources and searches

We performed an electronic search of the PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and relevant websites (www.crtonline.org, www.clinicaltrialresults.com, www.tctmd.com, www.cardiosource.com, and www.pcronline.com) were also searched from the inception of each database to March 2013 (search terms described in Supplementary material online, Table S1). The electronic search strategy was complemented by manual review of reference lists of included articles. References of recent reviews, editorials, and meta-analyses were also examined. Two individual investigators (S.H.K. and W.H.L.) performed screening of titles and abstracts, identified duplicates, reviewed full articles, and determined their eligibility. Disagreement between reviewers was resolved by discussions. The most updated data for each study were searched manually, and chosen for abstraction. Data extraction was done by one reviewer (S.H.K.), and subsequently cross-checked by a second reviewer (W.H.L.).

Risk of bias assessment

The quality of eligible RCTs was assessed using the Cochrane Collaboration's tool for assessing the risk of bias.18 Both manuscript and protocol, if available online, were reviewed for relevant information on quality. Risk of bias was assessed by one reviewer (K.P. or D.Y.K.), and cross-checked by a second reviewer (S.H.K.).

Study outcomes and definitions

The principal safety endpoint was definite or probable ST defined according to the Academic Research Consortium (ARC) within 1 year.19 If a study reported the incidence of ST in a way other than the ARC consensus (such as protocol-defined ST), the results were not included in the analysis. Other safety endpoints included definite ST, all-cause death, cardiac death, and MI. Efficacy endpoints were target lesion revascularization (TLR) and target vessel revascularization (TVR). Outcomes within 1 year as well as long-term outcomes (>1 year) were evaluated. For each clinical outcome, the most inclusive definitions were abstracted if possible, e.g. all-cause MI rather than target vessel-related MI, all TLR rather than ischaemia-driven or clinically driven TLR.

Data synthesis and analysis

A Bayesian random effects model for multiple treatment comparisons was constructed to compare clinical outcomes of different stent types. We used Bayesian extension of the hierarchical random-effects model proposed by Lumley for networks of multi-arm trials.20