Bioresorbable scaffolds in acute coronary syndrome: A promising alternative to drug-eluting stents or a step too soon?

Abstract

Bioresorbable scaffolds (BRS) represent a promising innovation in interventional cardiology, offering the potential to restore native arterial physiology while delivering drug-elution benefits. However, their role in acute coronary syndrome remains uncertain, given the higher thrombotic risk and lesion complexity in this population. This editorial reviews the current evidence surrounding bioresorbable scaffold use in acute coronary syndrome, particularly considering recent findings from Li et al in the World Journal of Cardiology, which suggest that contemporary bioresorbable scaffold platforms may provide mid-term outcomes comparable to drug-eluting stents under optimal procedural conditions. Despite these encouraging signals, this editorial emphasizes that the early experience with first-generation BRS was associated with increased thrombosis and target-lesion failure, particularly during the resorption phase. Newer-generation bioresorbable scaffold designs, coupled with refined implantation techniques and imaging guidance, have shown promising results, however, large, randomized controlled trials and long-term follow-up are essential to substantiate their clinical efficacy and safety. We advocate for a selective, evidence-driven approach to bioresorbable scaffold use in acute coronary syndrome, confined to low-complexity lesions in well-equipped centers with experienced operators. Robust randomized controlled trials, comprehensive imaging data, and transparent reporting are crucial to define the role of BRS in acute coronary syndrome and guide future clinical practice.

Key Words: Bioresorbable vascular scaffold; NeoVasc; Magnesium-based scaffold; Thrombosis; Pre-dilation; Sizing; Post-dilation

Core Tip: Bioresorbable scaffolds aim to provide temporary coronary support with drug delivery while ultimately restoring a device-free artery. In acute coronary syndrome, evidence remains cautious: First-generation polymeric scaffolds showed increased thrombosis during the resorption phase, and newer platforms require rigorous implantation discipline. The study by Li et al discussed here used the NeoVas sirolimus-eluting poly-L-lactic acid scaffold and reported comparable mid-term outcomes to drug-eluting stents, with reduced inflammatory biomarkers at 1 month. These signals are hypothesis-generating; definitive adoption requires randomized trials with imaging and long-term follow-up.

This editorial refers to “Medium-to-long term outcomes of bioresorbable scaffold treatment in patients with acute coronary syndrome” by Li et al, 2025; https://doi.org/10.4330/wjc.v17.i11.109287.

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INTRODUCTION

The urgent question today and the one central to the paper by Li et al[1] in the World Journal of Cardiology is whether modern Bioresorbable scaffolds (BRS) used with contemporary implantation technique, can safely and durably match modern drug-eluting stents (DES) in the high-risk setting of acute coronary syndrome (ACS). The available data is encouraging but not yet definitive. The extent to which modern BRS can match contemporary DES in ACS appears to depend on advances in scaffold design, careful patient and lesion selection, and optimal procedural technique.

BRS embody a compelling concept in contemporary interventional cardiology: To provide the temporary vessel support and drug delivery benefits of metallic DES while ultimately restoring a native, device-free arterial physiology. This technology promises to overcome the long-term limitations of permanent metallic implants by eliminating late stent thrombosis, allowing side-branch access, reducing imaging artefacts, and preserving future surgical options[2,3]. Early clinical experience suggests that, when implanted with meticulous lesion preparation, accurate sizing, and optimized post-dilatation under imaging guidance, contemporary BRS may achieve early outcomes comparable to modern DES in selected low-risk lesions[2,4]. The first generation of scaffolds was associated with increased thrombosis and target-lesion failure (TLF) during the resorption phase, and although these risks appear to be reduced with newer designs, definitive evidence from large, adequately powered randomized trials is lacking[2]. Given the inherently higher thrombotic and procedural risks associated with ACS and the current lack of comprehensive long-term evidence confirming the sustained safety and efficacy of BRS, their role in this setting should be considered exploratory rather than established. At present, BRS use in ACS is best regarded as a developing area of investigation; appropriate for carefully selected patients, managed by experienced operators, and ideally conducted within the framework of structured clinical research or prospective registries. This evolving context sets the stage for examining whether emerging data can substantiate the promise of BRS as a viable alternative to conventional DES in the management of ACS.

Recent observational data from Li et al[1] add to this evolving evidence base. In their single-center cohort of 128 ACS patients followed for up to three years, outcomes after implantation of a sirolimus-eluting BRS were broadly comparable to those achieved with a contemporary metallic DES, with no statistically significant difference in device-oriented composite endpoints at final follow-up. Interestingly, early post-procedural reductions in systemic inflammatory biomarkers (interleukin-6, C-reactive protein, tumor necrosis factor-α, and matrix metalloproteinase-9) were more pronounced in the bioresorbable scaffold group, suggesting a potentially more favorable short-term biological response[1].

In Li et al’s cohort study[1], the bioresorbable device was the NeoVas sirolimus-eluting bioresorbable scaffold, a poly-L-lactic acid (PLLA)-based polymeric platform. In earlier clinical descriptions of NeoVas, the total strut thickness is reported as 170 μm (160 μm backbone plus 10 μm coating/polymer layer), underscoring that favorable signals were achieved with a polymeric scaffold rather than a resorbable metal device[5] despite the general shift in the field toward thinner metallic scaffolds. This distinction is important because resorbable metallic scaffolds (e.g., magnesium-based systems) differ substantially in material properties and mechanical behavior from polymeric PLLA-based scaffolds, and outcomes across these categories should not be conflated.

The present study’s modest sample size, incomplete follow-up, and non-randomized design mean these findings should be interpreted as hypothesis-generating rather than definitive. The authors’ report nonetheless reinforces the notion that, under carefully controlled procedural conditions and with judicious patient selection, newer-generation bioresorbable platforms can achieve acceptable mid-term safety in ACS; an encouraging signal that warrants confirmation in larger, imaging-guided randomized trials.

THE EVIDENCE LANDSCAPE: WHAT WE KNOW AND WHAT REMAINS UNSETTLED

Large pooled analyses and randomized controlled trials (RCTs) of the early polymeric BRS (notably absorb) provided data on a time-varying hazard of device-related complications, concentrated in the period up to about 3 years (the scaffold resorption window), after which event rates tended to converge with metallic DES[3]. BRS events rose within the resorption period before stabilizing thereafter; an observation that focused the field on mechanistic drivers (strut thickness, under-expansion, malapposition) and on solutions rooted in implantation technique and device engineering[3].

Randomized long-term data have reinforced caution. The large ABSORB IV 5-year randomized trial experience reported higher TLF with BRS despite improved technique; device-thrombosis excess was concentrated early and through the first 3 years[3]. Similarly, the Amsterdam Investigator-initiated Absorb Strategy All-comers Trial’s 5-years follow-up confirmed an excess of device thrombosis with BRS vs DES[6]. This high-quality data explains why clinical practice retreated from routine BRS use and why regulatory and guideline positions remain conservative.

Yet not all BRS are the same. New-generation platforms with thinner struts, alternative resorbable metals (magnesium, iron), ultrathin polymer designs, and refined drug-elution schemes have reported encouraging mid-term outcomes in early human studies and first-in-human series[7]. The BIOMAG (DREAMS 3G) magnesium scaffold program and pooled NeoVas (sirolimus-eluting polymeric) data show comparable short- and mid-term angiographic and clinical performance in selected low-complexity lesions, although sample sizes remain modest and follow-up short compared with the classical DES evidence base[8]. Thus, the pendulum may be swinging toward cautious optimism, but the data remains preliminary and selective.

For clarity, “newer-generation BRS” includes two distinct trajectories: (1) Updated polymeric PLLA-based scaffolds (e.g., NeoVas) that retain a polymer backbone but incorporate design/drug-delivery refinements; and (2) Resorbable metallic scaffolds, most commonly magnesium-based systems, which represent a different material platform with distinct mechanical and degradation characteristics. Signals of safety/efficacy must therefore be interpreted within each platform type rather than pooled as a single category.

THE UNIQUE CHALLENGE OF EVALUATING BRS IN ACS

ACS presents a higher thrombotic status, more thrombus burden, and frequently more complex lesion morphology than stable coronary artery disease. These factors amplify any device-related susceptibility to thrombosis or malapposition. Consequently, ACS is the setting in which BRS must prove at least non-inferior to DES on both safety and efficacy. Trials and registries that include ACS patients are therefore necessary, but they require meticulous procedural technique [intravascular imaging, lesion preparation, correct scaffold sizing, and systematic post-dilatation (PSP)] and careful adjudication of events[9]. Observational series like the one by Li et al[1] can be hypothesis-generating but are prone to selection bias unless they transparently report device selection criteria, PSP adherence, intravascular imaging use, and complete follow-up.

Most randomized evidence shows a reproducible early- and mid-term safety signal (specifically higher device thrombosis and TLF) with first-generation polymeric bioresorbable vascular scaffolds during the resorption window. This evidence includes ACS patients in subgroup analyses and in the Amsterdam Investigator-initiated Absorb Strategy All-comers Trial substudy[10]. Newer devices and registries offer promising early and mid-term safety. Magnesium scaffolds show encouraging results in non-ST elevation ACS populations; however, evidence is either nonrandomized or from smaller RCTs that are not ACS-specific[8,11].

Adding to this body of evidence, a meta-analysis pooling data from five studies (two RCT and three observational cohorts) encompassing 1758 patients with ACS (BRS n = 917; DES n = 841) with a median follow-up of 24 months, provides further insight into comparative outcomes. The analysis demonstrated a higher incidence of TLR and device thrombosis among patients treated with BRS compared with those receiving DES. However, when TLR events attributable to thrombosis were excluded, the difference between groups was no longer statistically significant, indicating that scaffold thrombosis was the principal driver of the observed safety and efficacy gap. Importantly, no significant differences were found in all-cause mortality, cardiac death, target-vessel myocardial infarction, or overall TLF, suggesting that beyond thrombosis-related events, mid-term outcomes between the two devices are broadly comparable[12].

TECHNIQUE MATTERS: PSP IS NOT OPTIONAL

Good results with BRS correlate tightly with high-quality implantation and lesion preparation, correct scaffold sizing, and systematic PSP[9]. The absence of a PSP-adherence analysis or its components (balloon sizes/pressures, imaging guidance) makes it difficult to interpret single-center ACS BRS series. When implantation is optimized, outcomes are better; when technique is imperfect, the risk of scaffold thrombosis and target lesion failure increases, a point that has been validated repeatedly. Thus, any claim of equivalence between BRS and DES must be accompanied by detailed PSP data[9,13]. The study at hand[1] is strengthened by its strict adherence to PSP protocols, ensuring that the findings reflect the optimal performance of the BRS technology when best practices are rigorously followed.

INTERPRETING SHORT-TERM BIOLOGICAL SIGNALS IN TERMS OF INFLAMMATORY BIOMARKERS

The observed early decline in inflammatory biomarkers in patients treated with BRS, as reported by Li et al[1] provides an interesting physiological signal consistent with the theoretical appeal of a more biocompatible and transient vascular implant. Reduced levels of interleukin-6, C-reactive protein, tumor necrosis factor-α, and matrix metalloproteinase-9 within the first month after implantation may reflect less vessel wall irritation or procedural inflammation compared with metallic DES. A key limitation is the timing of biomarker assessment; such short-term biochemical responses should be interpreted with caution, as 1-month signals cannot be assumed to predict late scaffold-related risk during the resorption window (approximately the first 3 years for first-generation polymeric bioresorbable vascular scaffold) or very-late thrombotic events. Acute fluctuations in systemic inflammatory markers in ACS are strongly influenced by the underlying ischemic event, reperfusion injury, and procedural variables, and therefore may not represent a direct measure of device compatibility. Moreover, without further imaging data such as serial Optical Coherence Tomography or Intravascular Ultrasound demonstrating scaffold apposition, neointimal maturation, and resorption dynamics, these biomarker findings remain hypothesis-generating rather than confirmatory. Ultimately, long-term clinical outcomes and mechanistic imaging endpoints remain the definitive determinants of true biocompatibility and vascular healing. Within this context, the reported biomarker trends are best viewed as supportive preliminary evidence rather than proof of a durable biological advantage.

DEFINING THE EVIDENCE NEEDED TO CHANGE THE PRACTICE

The findings from the study by Li et al[1] should be viewed as part of a larger, incremental effort to redefine the clinical boundaries of BRS in ACS. They illustrate that, under optimal procedural conditions, contemporary BRS platforms can achieve acceptable medium-term outcomes even in patients traditionally considered at highest risk. Yet they also highlight the persistent evidence gap between encouraging physiological or biomarker signals and the level of proof required to alter clinical practice.

From a translational perspective, the central question is whether early biological signals such as reduced systemic inflammatory markers translate into improved endothelial healing and fewer scaffold-related adverse events during the resorption phase. From a clinical trial perspective, the current evidence underscores the need for adequately powered randomized studies in acute coronary syndrome populations with mandatory intracoronary imaging, standardized implantation technique, and long-term follow-up. From a practical implementation perspective, any potential benefit of BRS must be weighed against their procedural complexity, including the requirement for meticulous lesion preparation, accurate sizing, routine post-dilatation, and strict adherence to best-practice implantation protocols.

To influence current clinical practice, a multifaceted approach is required, starting with the need for large-scale, RCTs of use of BRS in ACS. These trials must incorporate modern BRS platforms, ensure stratification based on lesion complexity, and implement robust PSP and intravascular imaging protocols. Furthermore, research must extend follow-up periods beyond the typical resorption window, with this longer observation needing to include prespecified imaging schedules and the collection of patient-reported outcomes to fully understand long-term device performance. Enhanced transparency is also crucial for advancing the field, which involves openly sharing details on operator experience, adherence to PSP guidelines, lesion-level outcomes (especially concerning the use of hybrid devices), and independent adjudication of clinical events. Finally, head-to-head comparisons of various BRS technologies; specifically evaluating polymeric vs magnesium vs iron platforms; are necessary to distinguish between effects attributable to the device's material properties and those resulting from the implantation technique.

CONCLUSION

Routine use of BRS in ACS is premature. They are not a proven substitute for modern DES in the high-risk, heterogeneous ACS population. Their use should remain highly selective, confined to low-complexity lesions and experienced centers with meticulous procedural standards, including intravascular imaging and systematic PSP. While promising signals exist from new platforms and refined techniques, caution is mandated. BRS adoption must be strictly evidence-driven, occurring exclusively within large-scale RCTs or rigorously managed registries, not unselected routine use. Future progress hinges on robust data collection to definitively prove if theoretical advantages translate into reproducible clinical benefits for ACS patients.

ACKNOWLEDGEMENT

The author gratefully acknowledges Fathima Aaysha Cader [MBBS, MD, MRCP (United Kingdom), MSc (Oxon)] for her thorough revision of the English language and style.