Background
The introduction of coronary stents has revolutionized interventional cardiology. However, despite significant improvement over the years, traditional metallic stents have some intrinsic limitations. In fact, their permanent structure hinders surgical myocardial revascularization, physiological vessel remodeling and exposes patients to the risk of stent thrombosis for an indefinite time. Coronary bioresorbable scaffolds (BRS) were developed to overcome some of these limitations of standard metallic stents, especially to address late events after percutaneous coronary interventions (PCI) [
1]. BRS have been introduced in the last years as a novel promising approach to treat coronary stenosis by providing transient vessel support with drug delivery capability without the long-term limitations associated with vessel caging [
2]. This technology has the potential to overcome many of the safety concerns associated with drug-eluting stents, with possible clinical benefits [
3]. Although initial reports from single-arm studies in highly selected patients with simple coronary lesions were reassuring [
4‐
6], recent data from “real-life” registries and randomized controlled trials reported that the rates of scaffold-related are not negligible, also at long-term [
7‐
9].
The aim of this meta-analysis was to evaluate the efficacy and safety of BRS, compared with Everolimus-eluting stents (EES), using the data available from randomized trials, with a focus on long-term outcomes.
Discussion
This is the most comprehensive and updated meta-analysis of randomized studies comparing the long-term outcome after treatment of coronary artery disease with everolimus-eluting BRS or the equivalent metallic stent (EES). Summing up the best clinical evidence available to date, including 5 randomized studies and 5219 patients, we found that: a) BRS was associated with higher rates of TLF compared with EES; b) BRS was associated with higher rates of TV-MI compared with EES; c) BRS was associated with higher rates of DvT compared with EES; d) very-late DvT was higher with BRS compared with EES.
These results are not surprising, as similar trends were reported both in randomized and observational studies [
20,
21]. In particular, a previously published patient-level meta-analysis reported a higher incidence of device thrombosis with the BRS, compared with the equivalent metallic EES [
22]. However, their observation period was limited to 1 year and the studies were heterogeneous with regards to the enrollment of acute coronary syndrome and stable CAD patients [
23]. Similarly, a recent published meta-analysis of RCTs and observational studies had already reported a higher risk for TLF and DvT in BRS-treated patients [
24‐
26]. In this context, our results represent a robust confirmation of the association between use of BRS and a higher rate of DvT, and are the first report of differences in DvT early, late, and very-late after implantation.
The pathophysiology of scaffold thrombosis, and the possible explanations for the increased risk as compared to drug-eluting stents (DES), and particularly the role of the implantation technique [
27,
28] have been previously investigated. The implantation technique was not homogeneous across studies and instructions for use were not systematically followed in all studies. In fact, appropriate sizing of the balloon to be used for pre-dilation was not warranted in all patients enrolled in the Amsterdam Investigator-Initiated Absorb Strategy All-Comers Trial (AIDA). More generally, the BRS-specific implantation protocol, prescribing long inflation times and systematic high-pressure post-dilation with a non-compliant balloon, was not homogeneously adopted in all included studies, despite it was strongly recommended to achieve optimal implantation results [
29‐
31]. In addition, intravascular imaging guiding during BRS implantation has been reported to have a major positive impact on patients’ outcome but was not frequently used across the selected studies [
32‐
34]. Thus, a potential explanation for the observed increased risk of DvT in the randomized trials may relate to suboptimal implantation techniques, rather than to the intrinsic properties of BRS. Findings of this meta-analysis have relevant potential implications. The concern raised about BRS thrombosis, together with the lack of a clear advantage in terms of clinical efficacy, potentially undermines the future development of this promising class of coronary devices. In fact, the added value of the so-called vascular restoration therapy is still waiting for a proof of evidence, while interventional cardiologists have largely experienced the technical challenges in implanting the device, including worse trackability than best-in-class equivalent EES, longer procedural times, larger amounts of contrast medium necessary for successful implantation.
Collectively, the data emphasize the importance of appropriate lesion selection and accurate application of proper implantation technique. As well, a new generation of BRS should warrant a better radial strength, a sleeker endoluminal profile, a smaller footprint, and resorption processes that do not interact with the vessel wall.
Study limitations
Although no large heterogeneity was found between the randomized studies included in the present analysis, it entails possible limitations of the original studies included. There were differences in the study design, patients’ and procedural characteristics. To account for these potential sources of heterogeneity, we used a random effects model for all analyses. Even though the present analysis only included high quality, randomized studies, some potential source for bias may still persist. Unfortunately, a patient level meta-analysis couldn’t be possible because of lack of data. Additionally, in two of the trials, 2-year results had been presented but not have not been published yet [
15,
19]. In addition, since angina recurrence was not systematically reported in the original studies, we could not analyze the impact of BRS on this specific outcome. Moreover, we only focused on the Absorb, as this was the only type of BRS with several randomized studies and reporting long-term outcomes. Hence, our findings may not entirely apply to other BRS platforms. As well, the assessment of publication bias is limited by the small number of trials included, preventing a definitive exclusion of potential small study effect. Finally, further data on the impact of a BRS-specific implantation technique and the role of sizing on DvT are still needed, to confirm that BRS can deliver the same results as DES with the appropriate implantation techniques [
35].
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