NeoHexa stent at five years: Sirolimus power meets real-world endurance

Abstract

The drug-eluting stent, which combines a mechanical scaffold with the localized release of an antiproliferative drug to prevent in-stent restenosis caused by excessive tissue growth, represents a pivotal advancement in percutaneous coronary intervention. In this continually advancing field, establishing long-term efficacy and safety data is paramount. While excellent short-term results are now expected, the true clinical value of a drug-eluting stent is determined by its durability, its ability to maintain vessel patency and prevent adverse cardiac events for many years after implantation, especially in the complex, high-risk patients encountered in real-world practice. The retrospective study by Trehan et al, published in World Journal of Cardiology, provides a much-needed, long-term lens through which to view the performance of the NeoHexa sirolimus-eluting stent in an all-comer real-world Indian population. Here, we will discuss the recent progress in studying the long-term efficacy and safety of sirolimus-eluting stent.

Key Words: Stent; Safety; Outcome; Cardiovascular disease; Sirolimus-eluting stent

Core Tip: The retrospective study by Trehan et al provides critical five-year real-world evidence for the NeoHexa sirolimus-eluting stent, demonstrating exceptional long-term durability in a complex, all-comer patient population. With a remarkably low rate of major adverse cardiac events and target lesion revascularization, the findings underscore the stent's sustained safety and efficacy.

This editorial refers to "Five-year mean follow-up of NeoHexa sirolimus eluting coronary stent: A retrospective evaluation of long-term safety and efficacy" by Trehan et al, 2026; https://doi.org/10.4330/wjc.v18.i2.114636.

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INTRODUCTION

The advancement in interventional cardiology is not merely for incremental improvements in stent technology but for robust, long-term data that validates these devices in the unpredictable real-world clinical practice. The retrospective study by Trehan et al[1] published in World Journal of Cardiology, provides a much-needed, long-term lens through which to view the performance of the NeoHexa sirolimus-eluting stent (SES) in an all-comer real-world Indian population. This cohort is characterized by high acute coronary syndromes (ACS) prevalence and more advanced disease at initial presentation.

THE PHARMACOLOGICAL FOUNDATION: PRECISION MAMMALIAN TARGET OF RAPAMYCIN INHIBITION

Central to the performance of any drug-eluting stent is its pharmacologic agent. In the case of NeoHexa, this is sirolimus, a macrolide antibiotic derivative with potent immunosuppressive and antiproliferative properties[2]. Sirolimus’s mechanism of action, inhibiting the mammalian target of rapamycin (mTOR), is uniquely suited to cardiovascular applications[3,4]. By blocking mTOR, sirolimus arrests the cell cycle in the G1 phase[5], effectively halting the proliferation and migration of vascular smooth muscle cells that drive neointimal hyperplasia and subsequent in-stent restenosis[2,6,7].

This targeted cytostatic action, as opposed to the cytotoxic effect of earlier drugs like paclitaxel, provides a more favorable safety profile[8]. As illustrated in recent molecular studies, this mechanism prevents the inflammatory cascade and vascular remodeling that typically leads to late stent failure[9-12]. The NeoHexa stent features a cobalt-chromium alloy platform with 60 μm strut thickness, a biodegradable polymer, and designed to release sirolimus over 28 days (60% within 7 days). Unlike permanent polymers, which may induce chronic inflammation, the biodegradable nature of this platform facilitates more natural vessel remodeling[13]. Sirolimus released from NeoHexa stent suppresses the initial hyper-proliferative response while allowing for eventual vessel healing. This elegant pharmacological strategy underpins its beneficial outcome in interventional cardiology[14,15].

CLINICAL OUTCOMES AND COMPARATIVE EFFICACY

The findings of this study are undoubtedly encouraging. Reporting a remarkably low cumulative major adverse cardiac event (MACE) rate of 4.32% and a target lesion revascularization (TLR) rate of 1.76% over a mean follow-up of more than five years is a testament to the durable synergy between the stent platform and its sirolimus coating. The superior performance of NeoHexa in this all-comer population suggests that modern ultra-thin strut platforms combined with bioresorbable coatings may mitigate the long-term “catch-up” phenomenon seen in earlier generations.

Though cross-trial comparisons require caution due to population differences, NeoHexa’s 5-year MACE and TLR compare favorably when compared to other contemporary SES (Table 1)[1]. For example, 5-year MACE rates of 17.4% for CYPHER in the SORT OUT IV trial[16]. Ultimaster stent showed a TLR of 9.4% at 5-year post follow up in the CENTURY II study. Ischemia-driven TLR of 5.9% for Orsiro in the BIOFLOW V trial[17], while 5-year TLR of 9.4% for Ultimaster stent in the CENTURY II study[18]. These outcomes hold particular significance given the study’s population, which included a high proportion of patients with ACS (81.9%) and a substantial number with multivessel disease (58.1%). While the original study did not report outcomes by ACS subtype (e.g., acute ST-segment elevation myocardial infarction vs non-ST-segment elevation myocardial infarction), this gap highlights the need for finer subgroup analyses in future studies.

Table 1 5-year outcomes of NeoHexa vs contemporary drug-eluting stents.

Stent system	Ref.	5-year major adverse cardiac event	5-year target lesion revascularization	Key feature
NeoHexa	Trehan et al[1]	4.32%	1.76%	Biodegradable polymer
Orsiro	BIOFLOW V	8.0%-18.0%	5.9%	Ultrathin struts (60 μm)
Ultimaster	CENTURY II	N/A	9.4%	Bioresorbable coating
CYPHER	SORT OUT IV	17.4%	N/A	Durable polymer
MiStent	DESSOLVE I/II	15.1%	3.5%	Crystalline sirolimus
XIENCE	SPIRIT II	8.0%-15.0%	4.0%-6.0%	Cobalt-chromium everolimus-eluting stents

N/A: Not applicable.

Contemporary drug-eluting stents, particularly newer-generation sirolimus- and everolimus-eluting platforms, have demonstrated good long-term efficacy and durability, with 5-year MACE rates ranging from approximately 8%-18% and TLR rates of approximately 3%-6%[16,19,20], depending on patient risk and lesion complexity. These outcomes reflect substantial advances in stent design, polymers, and drug delivery, but event accrual continues over time, especially in complex and ACS populations. The NeoHexa stent’s 5-year outcomes appear favorable and suggest durable clinical performance, while underscoring the need for direct comparative trials to contextualize these findings against contemporary drug-eluting stents benchmarks.

SUBGROUP INSIGHTS AND PATHOPHYSIOLOGICAL PREDICTORS

The true depth of this analysis is revealed in its subgroup explorations. The stark contrast in MACE rates between diabetic and non-diabetic patients (8.8% vs 2.9%) is a powerful reminder that the patient’s underlying pathophysiology remains a dominant predictor of long-term outcome. This finding aligns with recent evidence suggesting that hyperglycemia-induced neoatherosclerosis can bypass the protective effects of drug elution[21-24]. This may stem from exaggerated inflammation, endothelial dysfunction, and neoatherosclerosis due to hyperglycemia, which can impair vessel healing and amplify restenosis despite mTOR inhibition by sirolimus[25,26].

This finding underscores the critical importance of aggressive secondary prevention and holistic patient management. Conversely, the lack of a significant difference in MACE between ACS and non-ACS subgroups (relative risk = 1.19, 95%CI: 0.47-3.04; P = 0.82) is reassuring, highlighting the stent's applicability in both elective and urgent scenarios. As shown in Figure 3 of the study[1], the Kaplan-Meier curve for MACE-free survival demonstrate a gradual but slow increase in event rates over time, reinforcing the need for sustained patient monitoring.

METHODOLOGICAL CONSIDERATIONS AND FUTURE DIRECTIONS

Naturally, as with any retrospective, single-center analysis, the results must be interpreted within the context of its methodological constraints. The retrospective design and lack of angiographic follow-up limit insights into asymptomatic restenosis. The inability to include 124 of 864 initially eligible patients (14.4% loss) due to loss to follow-up introduces the possibility of selection bias. The reported TLR rate of 1.76% reflects clinically driven revascularization, and the absence of systematic angiographic follow-up means that cases of asymptomatic restenosis could have been missed and the true angiographic restenosis rate may be higher.

To address these uncertainties, future investigations should employ intravascular imaging techniques such as optical coherence tomography or intravascular ultrasound to visualize the quality of the neointimal bridge[27-31]. A sensitivity analysis assuming worst-case scenarios (e.g., if all lost patients had MACE) would test the robustness of the 4.32% MACE rate. Furthermore, the lack of a direct control group limits definitive comparative conclusion.

CONCLUSION

In summary, the work by Trehan et al[1] delivers a strong and positive message about the long-term viability of the NeoHexa SES. It successfully bridges a gap in the evidence by providing a five-year perspective from a real-world setting. While the retrospective design advises a degree of caution, the consistently low event rates and high clinical success rate are promise. For now, it offers clinicians reassuring evidence of durable performance when using this stent in their daily practice. Continued monitoring of diverse patient cohorts remains essential to refine stent selection in the era of personalized interventional cardiology. Future studies should focus on prospective, multicenter designs with protocol-mandated imaging to validate these findings and explore NeoHexa’s efficacy in high-risk subgroups like diabetics.