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Patients with neoatherosclerosis (NA) observed at 3-7 years after percutaneous coronary intervention showed worse outcomes.
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Stents with NA at 3-7 years after implantation showed more stent failure.
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NA at very late phase after stenting may help identify high-risk patients.
Abstract
Background
Clinical significance of neoatherosclerosis (NA) observed at very late phase remains undetermined. We sought to investigate the association between NA observed by optical coherence tomography (OCT) 3–7 years after stenting and subsequent clinical outcomes.
Methods
We investigated previously implanted stents without stent failure in the institutional OCT database at Tsuchiura Kyodo General Hospital. Qualitative and quantitative OCT analyses were performed. In patient-based analysis, major adverse cardiac events (MACE) included all-cause death, non-fatal myocardial infarction, and clinically driven revascularization. MACE-free survival rate was compared between patients with any stent showing NA (NA group) and those without NA (non-NA group). In stent-based analysis, the stent failure including target-lesion revascularization and stent thrombosis after the belated OCT examination were assessed.
Results
A total of 187 patients with 308 stents undergoing belated OCT examination 3–7 years after implantation were investigated. Median duration from implantation to the belated OCT was 4.8 (3.8-5.8) years and NA was identified in 48 stents (15.6%) in 36 patients (19.3%). In patient-based analysis, during the median of 2.9 (2.1-3.6) years after belated OCT, MACE occurred in 9 patients (25.0%) with at least one stent showing NA (NA group) and 9 patients (6.0%) without NA (non-NA group) (p=0.002). Cox regression analysis revealed that NA was an independent predictor of MACE [hazard ratio (HR) 4.14 (1.58- 10.8), p=0.004]. In stent-based analysis, 7 stent failures were documented (stents with NA 10.0% vs. stents without NA 0.8%, p<0.01). NA was a significant predictor of stent failure [HR 9.17 (1.67- 50.3), p=0.011] at OCT examinations.
Conclusions
NA observed by OCT 3-7 years after implantation was associated with subsequent worse clinical outcomes in both patient-based and stent-based analysis.
Ten-year clinical outcomes of first-generation drug-eluting stents: the Sirolimus-Eluting vs. Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) VERY LATE trial.
7-Year outcomes of a randomized trial comparing the first-generation sirolimus-eluting stent versus the new-generation everolimus-eluting stent: The RESET Trial.
. Previous optical coherence tomography (OCT) studies consistently showed that very late stent thrombosis is attributable to neoatherosclerosis (NA) as well as malapposed or uncovered struts [
Optical coherence tomography findings in patients with coronary stent thrombosis: a report of the PRESTIGE Consortium (Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort).
]. NA was originally defined in pathological studies as atherosclerotic changes of neointima observed within the stented segments and characterized by accumulation of lipid-laden foamy macrophages, necrotic core formation, or calcification within neointima [
, which may occur in months to years following stent implantation, whereas atherosclerosis in native coronary arteries develops over decades. In clinical practice, intracoronary imaging modalities including coronary angioscopy and OCT enabled in-vivo assessment of NA [
In-stent yellow plaque at 1 year after implantation is associated with future event of very late stent failure: The DESNOTE Study (Detect the Event of Very late Stent Failure From the Drug-Eluting Stent Not Well Covered by Neointima Determined by Angioscopy).
. In particular, OCT has been used for the identification of neoatherosclerotic change such as lipid-laden neointima, macrophage infiltration, and plaque rupture, because of the high-resolution image quality of approximately 10-20 µm [
Appearance of lipid-laden intima and neovascularization after implantation of bare-metal stents extended late-phase observation by intracoronary optical coherence tomography.
]. In previous studies, NA observed by coronary angioscopy at 1 year or by OCT at more than 12 months after implantation were reported to be associated with subsequent clinical events, which may suggest the clinical implication of morphological assessment of neointima long-term follow-up after stenting [
In-stent yellow plaque at 1 year after implantation is associated with future event of very late stent failure: The DESNOTE Study (Detect the Event of Very late Stent Failure From the Drug-Eluting Stent Not Well Covered by Neointima Determined by Angioscopy).
The impact of in-stent neoatherosclerosis on long-term clinical outcomes: an observational study from the Kobe University Hospital optical coherence tomography registry.
. Nevertheless, there is a paucity of literature regarding clinical significance of NA observed after longer duration of more than 3 years. The current study aimed to investigate the prognostic value of NA observed in stents after a very long-term duration of the median of 4.8 years after implantation.
Methods
Study population
The institutional OCT database at Tsuchiura Kyodo General Hospital included OCT examinations between October 2012 and December 2019. A search was performed to identify previously implanted stents without stent failure requiring immediate revascularization (Fig. 1). We defined the belated OCT examination as an OCT observation performed at between 3 and 7 years after stent implantation. In general clinical practice of the institution, invasive angiography was performed as a part of an institutional registry study to examine the long-term healing status of coronary stents for whom informed consent was obtained or at physicians’ discretion based on the institutional consensus for the indication which included the need for the cessation of antiplatelet therapy for non-cardiac surgery or high-bleeding-risk procedures, chest discomfort suggestive of angina, or inconclusive findings on noninvasive tests of myocardial ischemia. Thereafter, OCT was performed based on the operators’ discretion for the evaluation of neointimal findings including NA within the stents. Stents requiring revascularization based on the belated coronary angiography or those causing myocardial ischemia at the time of the coronary angiography were excluded from the subsequent analysis as described below. We enrolled all stent types including bare-metal stent (BMS), 1st-generation DES, and 2nd-generation DES. Exclusion criteria were: (1) stents implanted within a stent, (2) in-stent restenosis inducing myocardial ischemia or requiring revascularization, (3) stents with poor OCT image quality, (4) stents in bypass grafts, (5) stents in patients with hemodialysis, and (6) the absence of clinical follow-up data more than 1 year after the belated OCT examination. In patient-based analysis, we defined NA group as patients with at least one stent with lipid-laden neointima which met inclusion criteria. The study protocol was approved by the ethics committee of Tsuchiura Kyodo General Hospital and conformed to the Declaration of Helsinki statement on research involving humans. Informed consent for the institutional OCT database registration and potential future analysis of the data were provided by all participants after a complete explanation of the protocol and potential risks related to imaging before catheterization.
Fig. 1Study population. From the institutional database of 2,943 OCT examinations, we selected 308 stents in 187 patients who underwent belated OCT examinations 3–7 years after stent implantation for the final analysis. For patient-based analysis, patients were divided into two groups: patients with NA in ≥1 observed stent meeting inclusion criteria (NA group) and patients without NA in any stent (non-NA group).
Frequency-domain OCT system (C8-XRTM or ILUMIEN OCT Intravascular Imaging System, Abbott Vascular, Santa Clara, CA, USA) were used in the present study. Techniques for the acquisition of OCT image have been described elsewhere [
Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the international working group for intravascular optical coherence tomography standardization and validation.
Safety and feasibility of a new non-occlusive technique for facilitated intracoronary optical coherence tomography (OCT) acquisition in various clinical and anatomical scenarios.
. All cross-sectional OCT images were analyzed at 0.1-mm intervals excluding the overlapped segments. Qualitative OCT analysis included the presence of lipid-laden neointima, macrophage, thrombus, and plaque rupture within the stents. Lipid was characterized by a signal-poor region with overlying signal-rich band on OCT [
Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis.
. In the present study, lipid-laden neointima was defined as the presence of lipid within the neointima which precluded visualization of stent strut behind the lesion in more than 3 continuous frames (0.3 mm) (Fig. 2) [
Tissue characterization of in-stent neointima using optical coherence tomography in the late phase after bare-metal stent implantation–an ex vivo validation study.
Ex vivo assessment of neointimal characteristics after drug-eluting stent implantation: Optical coherence tomography and histopathology validation study.
]. NA was defined as a stent with lipid-laden neointima. Macrophage accumulation was defined by OCT as signal-rich, distinct, or confluent punctate regions that exceeded the intensity of background speckle noise that shows frame-by-frame variability of signal but does not preclude strut visibility. Quantitative OCT measurement included lipid length, lipid arc, minimum lumen area (MLA) at the stented segment, minimum stent area (MSA), and stent mal-apposition. As for strut apposition, we measured the distance between the center of blooming artifact and luminal surface, and when the distance was greater than strut thickness, the strut was considered malapposed. Strut apposition was determined at 0.1-mm intervals throughout the stent excluding the segment with side branches or stent overlap. Stents with any malapposed strut was defined as malapposed stent. Inter- and intra-observer variability for the diagnosis of NA were assessed.
Fig. 2The definition of NA on OCT. Cross-sectional OCT images were analyzed at 0.1-mm intervals for qualitative and quantitative assessment except for the segments with overlapping stent. A representative image of lipid-laden neointima on OCT is shown. Lipid-laden neointima was characterized as signal-poor region within the intima which precluded the visualization of underlying stent struts (white arcs) in >3 contiguous frames (0.3 mm), which was differentiated from macrophage infiltration showing signal-rich region accompanied by background speckle noise that shows frame-by-frame variability of signal. NA was defined as having lipid-laden neointima. Lipid length was measured as a length of segments that met the definition of lipid-laden neointima.
The median clinical follow-up period after the belated OCT examination was 2.9 (2.1- 3.6) years. Clinical outcome data were obtained by reviewing patients’ medical records or telephone interview. Laboratory data obtained within a month before the belated OCT examination were used for the analysis. In patient-based analysis, major adverse cardiac events (MACE) included all-cause death, non-fatal myocardial infarction (MI), and clinically driven revascularization. MACE-free survival rate was compared between patients with any stent showing NA (NA group) and those without NA (non-NA group). In stent-based analysis, the stent failure including target-lesion revascularization and stent thrombosis after the belated OCT examination were assessed. Scheduled revascularizations were indicated based on the findings of the belated OCT examination and revascularizations within 3 months after the belated OCT examination were disregarded as adverse events. Cumulative incidence of stent failure was compared between stents with NA and those without.
Statistical analysis
Data were analyzed on per-patient and per-stent basis. Categorical variables were presented as counts and proportions, and comparisons between groups were performed using the chi-square test or Fisher's exact test depending on the data distribution. Continuous variables showing a normal distribution were expressed as mean ± standard deviation, and compared by means of Student's t-test. Non-normally distributed continuous variables were expressed as median (25-75th percentile), and the Mann-Whitney U test was used to compare groups. Inter- and intra-observer variability for the diagnosis of NA were estimated by means of kappa coefficient (k). Survival curves were depicted using Kaplan-Meier estimates and compared with the log-rank test. Univariable and multivariable Cox proportional hazard models were determined to identify the predictors of adverse events after the belated OCT examinations. Variables showing a p-value less than 0.10 were entered for the forward stepwise regression analysis to optimize the multivariable model. All statistical analyses were performed with SPSS 22.0 (SPSS Inc., Chicago, IL, USA) or R version 3.5.0. A p-value less than 0.05 was considered statistically significant.
Results
Patient and stent characteristics
Our OCT database included a total of 2,943 OCT examinations in 2,097 patients. From a total of 2,180 stents in 1,103 patients identified in the registry, we selected 353 stents in 217 patients which underwent belated OCT examination at between 3 and 7 years after stent implantation for further investigation. After exclusions, final dataset included a total of 308 stents in 187 patients (Fig. 1), which accounted for 5.2% of all the stents (n=5890) implanted in the institution during the same period in which the study stents were implanted. NA was observed in 48 stents (15.6%) from 36 patients, who were categorized into NA group. Remaining 260 stents without NA included 9 stents from NA group patients and 251 stents from non-NA group patients. The baseline patient characteristics according to NA or non-NA groups at the time of belated OCT examination are summarized in Table 1 [
]. Low-density lipoprotein (LDL) cholesterol level was significantly higher in NA group than in non-NA group (p=0.001), whereas no significant difference was observed in the prevalence of statin or ezetimibe use. There was no significant difference in type of statin, type of anti-hypertensive drugs, or type of anti-diabetic treatment between the two groups. Stent characteristics are summarized in Table 2. No significant differences were observed between the two groups in lesion location and the baseline clinical presentation at the time of stent implantation. The majority of the stents was 2G-DES and there was no significant difference in the prevalence of each stent type. Stent length was greater in the NA group than in the non-NA group. Stent age, which indicated the duration from the index PCI to the belated OCT examination, was 4.8 (3.9-5.8) years in the total cohort and was greater in the NA group than in the non-NA group.
Five-year optical coherence tomography in patients with ST-segment-elevation myocardial infarction treated with bare-metal versus everolimus-eluting stents.
The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study.
Five-year optical coherence tomography in patients with ST-segment-elevation myocardial infarction treated with bare-metal versus everolimus-eluting stents.
The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study.
Five-year optical coherence tomography in patients with ST-segment-elevation myocardial infarction treated with bare-metal versus everolimus-eluting stents.
The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study.
Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis.
Tissue characterization of in-stent neointima using optical coherence tomography in the late phase after bare-metal stent implantation–an ex vivo validation study.
Ex vivo assessment of neointimal characteristics after drug-eluting stent implantation: Optical coherence tomography and histopathology validation study.
Five-year optical coherence tomography in patients with ST-segment-elevation myocardial infarction treated with bare-metal versus everolimus-eluting stents.
The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study.
Tissue characterization of in-stent neointima using optical coherence tomography in the late phase after bare-metal stent implantation–an ex vivo validation study.
Ex vivo assessment of neointimal characteristics after drug-eluting stent implantation: Optical coherence tomography and histopathology validation study.
Five-year optical coherence tomography in patients with ST-segment-elevation myocardial infarction treated with bare-metal versus everolimus-eluting stents.
The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study.
Association between coronary atherosclerosis progression and in-stent neoatherosclerosis in patients with ST-elevation myocardial infarction at five-year follow-up.
Safety and feasibility of a new non-occlusive technique for facilitated intracoronary optical coherence tomography (OCT) acquisition in various clinical and anatomical scenarios.
Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis.
Tissue characterization of in-stent neointima using optical coherence tomography in the late phase after bare-metal stent implantation–an ex vivo validation study.
Ex vivo assessment of neointimal characteristics after drug-eluting stent implantation: Optical coherence tomography and histopathology validation study.
Five-year optical coherence tomography in patients with ST-segment-elevation myocardial infarction treated with bare-metal versus everolimus-eluting stents.
OCT findings of stents were summarized according to the presence or absence of NA in Table 2. Thrombus and macrophage accumulation were more frequently observed in stents with NA than in those without NA, whereas no significant differences were observed in the prevalence of stent mal-apposition, MLA, and MSA between the two groups. Plaque rupture was not detected within the stented segment of the present study. Inter- and intra-observer variability for the diagnosis of NA was k= 0.89 and k= 0.93, respectively.
Clinical outcomes
In patient-based analysis, during the median follow-up period of 2.9 (2.1- 3.6) years after the belated OCT examination, 18 MACEs (9.6%) occurred in the total cohort. The details of MACEs are shown in Table 3. Significantly higher MACE rate was observed in the NA group than in the non-NA group during the follow-up observation, which was mainly attributed to more target vessel revascularizations in the NA group. In the NA group, two non-fatal MIs occurred in non-target vessels whereas no MI was observed in the non-NA group. Non-fatal MI and target vessel revascularization were significantly more frequent in the NA group than in the non-NA group, whereas only non-significant trend was observed toward more frequent non-target vessel revascularization in the NA group as compared with the non-NA group. In Kaplan-Meier analysis, MACE-free survival rate was significantly worse in the NA group than in the non-NA group (Fig. 3A). Univariable and multivariable Cox proportional hazard models were exercised to identify the predictors of MACE (Table 4). In univariate analysis, NA group was a significant predictor of MACE. In multivariable model adjusted with age and diabetes, NA group remained an independent predictor of MACE.
Table 3Patient-based and stent-based adverse events during clinical follow-up.
Patient-based adverse events
Overall
NA group
Non-NA group
p-value
N
187
36
151
Clinical follow-up after OCT examination, year
2.9 [2.1-3.6]
3.1 [2.6-3.6]
2.8 [2.0-3.6]
0.27
MACE
18 (9.6)
9 (25.0)
9 (6.0)
<0.01
All-cause death
4 (2.1)
1 (2.8)
3 (2.0)
0.58
Non-fatal MI
2 (1.1)
2 (5.6)
0 (0.0)
0.04
TVR
8 (4.3)
5 (14.0)
3 (2.0)
<0.01
Non-TVR
6 (2.7)
3 (8.3)
3 (2.0)
0.09
Stent-based adverse events
Overall
Stents with NA
Stents without NA
p-value
N
308
48
260
Stent failure
7 (2.3)
5 (10.0)
2 (0.8)
<0.01
Restenosis requiring revascularization
7 (2.3)
5 (10.0)
2 (0.8)
<0.01
Stent thrombosis
0 (0.0)
0 (0.0)
0 (0.0)
1.00
Values are presented as median (interquartile range) or absolute numbers (%).
Fig. 3Event-free curves for patient-based and stent-based analysis. Kaplan-Meier analysis revealed a significantly worse MACE-free survival in the NA group than in the non-NA group in patient-based analysis (A). Kaplan-Meier analysis showed a significantly worse survival free from stent failure in stents with NA than in stents without NA of stent-based analysis (B).
In stent-based analysis, a total of 7 stent failures consisted of 7 clinically-driven revascularizations for stent restenosis (2.3%) and no stent thrombosis was documented. The prevalence of stent failure was significantly greater in stents with NA than those without NA (Table 3). Kaplan-Meier analysis revealed a significantly lower event-free survival rate in stents with NA as compared with those without NA (Fig. 3B). In univariable Cox proportional hazard analysis, NA and MLA were significant predictors of stent failure whereas stent type was not associated with the events. In multivariable analysis, NA remained an independent predictor of stent failure with adjustment with MLA (Table 5). Non-target vessel revascularizations were numerically more frequent in the NA group than in the non-NA group, which did not reach statistical significance (Table 3).
Table 5Univariable and multivariable Cox proportional hazard models for stent-based adverse cardiac events.
The current study investigated the clinical outcomes of patients with NA observed on OCT examination performed at very late phase between 3 and 7 years after implantation. Major findings of the present study were as follows: 1) NA was observed in 15.6% of non-restenotic stents on the belated OCT performed 3–7 years after implantation; 2) patients with NA 3-7 years after stent implantation showed worse clinical outcomes during the follow-up period of 2.9 years after the belated OCT examinations in comparison with patients who had no NA within the stents; 3) stents with NA 3-7 years after stent implantation showed more target lesion revascularization due to in-stent restenosis after the belated OCT examinations as compared with stents without NA.
Neoatherosclerosis 5 years after implantation
Since the clinical registries of stent thrombosis observed by OCT revealed that NA was one of the major mechanisms of stent thrombosis [
Optical coherence tomography findings in patients with coronary stent thrombosis: a report of the PRESTIGE Consortium (Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort).
], there has been increasing interest in NA as a potential therapeutic target for secondary prevention after stent implantation. Although the development of NA is reportedly associated with multiple factors [
. Nevertheless, the data on the incidence of NA at very late phase of more than 3 years are still limited. In a previous OCT study, prevalence of NA was compared in a prospective manner between BMS (n=32) and DES (n=32) at 5 years from implantation as a sub-study of a randomized trial comparing clinical outcomes in ST-segment elevation MI patients and the prevalence of NA was 25.8% in BMS and 16.1% in DES respectively, which were not statistically different [
Five-year optical coherence tomography in patients with ST-segment-elevation myocardial infarction treated with bare-metal versus everolimus-eluting stents.
]. Their results were consistent with the current study showing 15.6% of NA at the median age of 4.8 years which showed no significant association with stent types such as BMS and 2G-DES. In previous studies, DES was reported to develop NA earlier than BMS [
. It is speculated that dysfunctional endothelial coverage induced by the anti-proliferative effects of the eluted drugs contribute to the accelerated development of NA after DES implantation [
]. In addition, polymer coating may promote chronic inflammation which may contribute to NA. Although the delayed healing process and inflammation may last for several years after DES implantation, the endothelial function may recover shortly after complete elution of the drug, which may result in non-significant difference in the prevalence of NA between BMS and DES at 5 years.
NA and clinical outcomes
As NA increases over time, it is speculated that the clinical significance of NA may increase as the stent becomes older. However, the clinical significance of NA has not been fully elucidated. Kuroda et al. investigated a total of 314 stents in 175 patients which underwent follow-up OCT examinations more than 1 year after implantation [
The impact of in-stent neoatherosclerosis on long-term clinical outcomes: an observational study from the Kobe University Hospital optical coherence tomography registry.
]. They revealed that having a stent with NA at follow-up OCT examination was associated with MACE consisting of cardiac death, myocardial infarction, and TLR, as well as stent thrombosis, and suggested a potential implication of NA as a high-risk marker for subsequent events. However, as they included various age of stents at OCT examinations, it was not clarified if NA at any timing might be clinically relevant. The current study limited the duration of the belated OCT between 3 and 7 years in order to investigate the clinical significance of NA observed at very late phase more than 3 years. Consistently with the result shown by Kuroda et al., the current study demonstrated that the patients having a stent with NA had more frequent MACE as compared with those without NA, although the event-free survival curves seemed to diverge later than those in the previous report [
The impact of in-stent neoatherosclerosis on long-term clinical outcomes: an observational study from the Kobe University Hospital optical coherence tomography registry.
]. In addition to the target vessel revascularization, non-target vessel revascularizations, physically non-related to the stents with NA, were numerically more frequent in the NA group than in the non-NA group (8.3% vs. 2.0%, p=0.09). Taniwaki et al. reported that NA observed at 5 years was associated with angiographical progression of non-target lesions from the baseline angiography immediately after implantation, which revealed a close link between the in-stent neoatherosclerotic change and de novo atherosclerosis in the belated lesions, suggesting pan-vascular inflammation [
The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study.
]. Unlike previous clinical trials, LDL cholesterol by itself was not a significant predictor of MACE in the present study. In the current cohort, most patients (173/187, 93%) received lipid-lowering therapy using statins and the LDL cholesterol levels were both low in the NA group and the non-NA group with the median value of 94 mg/dl and 82 mg/dl, respectively. A previous meta-analysis of large clinical trials regarding the impact of lipid-lowering on cardiovascular outcomes estimated 21% proportional reduction of adverse vascular events per mmol/l in 5 years [
]. Therefore, the non-NA group in the present study may have 6.5% lower risk of MACE as compared with the NA group in 5 years based on the difference in LDL cholesterol level of 12 mg/dl between the groups. However, the impact of LDL cholesterol level on the outcomes could not be detected in 187 patients which is much smaller than previous large trials. In addition to the stented segments, previous studies showed that the presence of in-stent NA was associated with the progression of native coronary atherosclerosis in the non-culprit sites outside of stents [
The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study.
Association between coronary atherosclerosis progression and in-stent neoatherosclerosis in patients with ST-elevation myocardial infarction at five-year follow-up.
The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study.
] investigated 88 patients enrolled in the SIRTAX-LATE OCT study undergoing belated OCT examination at 5 years and found that patients with NA within a stent had greater lumen reduction on angiogram in untreated, native coronary artery from baseline to the belated OCT examination, which may indicate the susceptibility to pan-vascular atherosclerosis due to patient-based risks in addition to the local atherosclerotic change in patients with neoatherosclerosis. Corroborating the previous studies, the current study showed a non-significant trend toward more frequent non-target vessel revascularization in patients with NA than in the non-NA group (8.3% vs. 2.0%, p=0.09).
Limitations
This study has several limitations that should be considered when interpreting the result. First, this was a retrospective observational study performed in a single center, therefore, selection bias may exist. Second, all the stents in the patients were not necessarily evaluated by OCT. In other words, some patients had stents that were not evaluated by OCT. Third, we excluded stent-in-stent lesions and overlapping segments from the analysis, both of which can affect the formation of NA and stent failure. Fourth, given the retrospective analysis, selection of stent types was left to the operator's discretion. Particularly, BMS was more frequently used for acute coronary syndrome patients than was DES in certain periods, which may have caused a bias. Finally, this study lacked complete information on laboratory data and medication status at the time of the index procedure and during the study period. In particular, LDL cholesterol at the time of belated OCT examination was used for analysis although the value may have changed later and affected the outcomes.
Conclusion
In-stent NA observed by OCT 3–7 years after implantation was associated with subsequent worse clinical outcomes including all-cause deaths, non-fatal MI, and clinically driven revascularization in both patient-based and stent-based analysis. NA at the very late phase after stenting may help identify high-risk patients of subsequent adverse events.
Disclosures
None.
Acknowledgments
None.
Funding
None.
References
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10-Year clinical outcome after randomization to treatment by sirolimus- or paclitaxel-eluting coronary stents.
Ten-year clinical outcomes of first-generation drug-eluting stents: the Sirolimus-Eluting vs. Paclitaxel-Eluting Stents for Coronary Revascularization (SIRTAX) VERY LATE trial.
7-Year outcomes of a randomized trial comparing the first-generation sirolimus-eluting stent versus the new-generation everolimus-eluting stent: The RESET Trial.
Optical coherence tomography findings in patients with coronary stent thrombosis: a report of the PRESTIGE Consortium (Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort).
In-stent yellow plaque at 1 year after implantation is associated with future event of very late stent failure: The DESNOTE Study (Detect the Event of Very late Stent Failure From the Drug-Eluting Stent Not Well Covered by Neointima Determined by Angioscopy).
Appearance of lipid-laden intima and neovascularization after implantation of bare-metal stents extended late-phase observation by intracoronary optical coherence tomography.
The impact of in-stent neoatherosclerosis on long-term clinical outcomes: an observational study from the Kobe University Hospital optical coherence tomography registry.
Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the international working group for intravascular optical coherence tomography standardization and validation.
Safety and feasibility of a new non-occlusive technique for facilitated intracoronary optical coherence tomography (OCT) acquisition in various clinical and anatomical scenarios.
Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis.
Tissue characterization of in-stent neointima using optical coherence tomography in the late phase after bare-metal stent implantation–an ex vivo validation study.
Ex vivo assessment of neointimal characteristics after drug-eluting stent implantation: Optical coherence tomography and histopathology validation study.
Five-year optical coherence tomography in patients with ST-segment-elevation myocardial infarction treated with bare-metal versus everolimus-eluting stents.
The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study.
Association between coronary atherosclerosis progression and in-stent neoatherosclerosis in patients with ST-elevation myocardial infarction at five-year follow-up.
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