Comparison of the Efficacy of Everolimus-Eluting Stents and Paclitaxel-Eluting Balloon Angioplasty for Coronary In-Stent Restenosis: A Systematic Review and Meta-Analysis

Abstract

Background:

The aim of the study was to systematically evaluate and compare the efficacy of everolimus-eluting stents (EESs) and paclitaxel-coated balloons (PCBs) in treating patients with in-stent restenosis (ISR).

Methods:

We performed a comprehensive search of the PubMed, Cochrane Library, Web of Science, and Embase databases up to August 2024. Two researchers independently conducted literature retrieval, screening, data inclusion, and quality assessment. A collaborative meta-analysis was performed using Stata 17.0.

Results:

A total of ten randomized controlled trials (RCTs) were included, all assessed using the Cochrane quality assessment tool and were categorized as having a low risk of bias. The analysis revealed a significantly higher need for target lesion revascularization in the PCB group compared to the EES group (odds ratio (OR) = 2.74, 95% confidence interval (CI) (1.80–4.16), p < 0.001, I² = 38.6%). There were no significant differences between the EES or PCB treated ISR patients in terms of all-cause mortality, cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis within one year. Subgroup analyses based on ISR causative factors showed consistent results with overall findings and significantly reduced heterogeneity.

Conclusion:

PCBs are associated with a higher frequency of target lesion revascularization compared to EES in the treatment of ISR. However, there are no significant differences in other outcome indicators. Therefore, EES is recommended as the preferred treatment for ISR in clinical decision-making.

The INPLASY registration:

INPLASY202480079, https://inplasy.com/inplasy-2024-8-0079/.

Graphical abstract

Keywords

in-stent restenosis / paclitaxel-coated balloon / everolimus-eluting stent / systematic review/meta-analysis

1. Background

Percutaneous coronary intervention (PCI) is primarily used to treat severe coronary artery stenosis [1, 2, 3], often involving the implantation of bare-metal stents (BMSs) or drug-eluting stents (DESs). While BMSs are widely used, they frequently lead to intimal hyperplasia, which can result in in-stent restenosis (ISR). Although DESs are designed to inhibit neointimal proliferation, restenosis remains a persistent challenge [4, 5]. Therefore, the treatment of ISR patients is a significant clinical burden [6, 7]. In clinical practice, ISR is characterized by the development of neovascular lesions at the stent edges or within the stent, typically occupying more than 50% of the vessel’s diameter. This condition remains a significant limitation of PCI [6, 8]. Despite its relatively low incidence, ISR remains a significant issue, especially as PCI is applied to more high-risk patients and complex lesions. Reports indicate that 5% to 20% of patients experience restenosis [7, 9, 10, 11, 12], which, although often considered benign, is associated with a higher incidence of myocardial infarction [13]. Consequently, it is crucial to focus on the treatment of ISR patients. Current approaches for treating ISR include traditional balloon angioplasty, laser atherectomy, re-implantation of either a BMS or DES, and drug-coated balloon (DCB) angioplasty [6].

Despite the array of available technologies for treating ISR patients, determining the optimal treatment method for ISR remains unsolved [6, 7, 14, 15]. Recent clinical trial guidelines suggest that both DESs and DCBs are recommended for treating ISR [6, 16, 17, 18, 19, 20, 21]. The DES are coated with antiproliferative drugs such as everolimus, zotarolimus, or paclitaxel [22]. Upon implantation, the attached drugs are gradually released, effectively inhibiting neointimal proliferation [23]. Currently, second-generation DESs offer improved efficacy compared to earlier models. Similarly, DCB surfaces are also coated with antiproliferative drugs, such as paclitaxel, but they deliver the drug directly to the lesion site without the need for a permanent stent. This targeted drug delivery helps control intimal proliferation while minimizing the risks associated with stent implantation. Studies have shown that DES treatment yields better angiographic and clinical outcomes compared to DCB treatment, primarily due to a reduced need for repeat vascular reconstruction [17, 18]. The primary limitations of DESs include the risk of stent thrombosis and secondary stenosis, attributed to their multiple metal layers. In contrast, DCB treatment addresses these concerns by reducing late lumen loss [24, 25]. Despite these advantages, the optimal strategy for treating ISR remains unresolved. This study aimed to compare the short-term (1-year) and long-term (3-year) efficacy of paclitaxel-coated balloon (PCB) catheters (Sequent Please PEB, B. Braun, Melsungen, Germany) and everolimus-eluting stents (EESs) (XIENCE, Abbott Vascular, Santa Clara, CA) in the treatment of ISR through a systematic review and meta-analysis, and to provide evidence-based guidance for clinical treatment strategies.

2. Methods

This study was conducted according to the internationally recognized guidelines outlined in the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)” [26]. It has been registered on the INPLASY platform, an international registry for research protocols. The registration includes a complete research protocol, with the registration number INPLASY202480079. This study is available at: https://inplasy.com/inplasy-2024-8-0079/, last accessed on August 16, 2024.

2.1 Search Strategy

We conducted a comprehensive literature search on the treatment of ISR with PCBs or EESs across multiple databases, including PubMed, EMbase, Cochrane Library, and Web of Science. The search included studies published up to August 2024. The search utilized a combination of MeSH terms and free-text keywords. To ensure a thorough search, additional manual searches were performed. The search terms included (“in-stent restenosis” OR “obstruction of the stent”) AND (“paclitaxel-coated balloon” OR “drug-coated balloon”) AND (“everolimus-eluting stent” OR “drug-eluting stent”).

2.2 Study Selection

Two researchers independently screened the literature and extracted data, with cross-verification of results to ensure accuracy. Disagreements between the researchers were resolved either through discussion or by consulting a third party. The inclusion criteria for this meta-analysis were as follows: (1) The study type was limited to randomized controlled trials (RCTs); (2) Studies included patients who developed ISR following PCI; (3) Interventions included the use of PCB or EES for the treatment of ISR; (4) The study focused on outcomes including one-year all-cause mortality, cardiac death, myocardial infarction, target lesion revascularization, target vessel revascularization, and stent thrombosis. Exclusion criteria included: (1) Studies that were duplicate publications; (2) Studies that did not report relevant outcome measures; (3) Studies for which the full text could not be accessed; (4) Other meta-analyses, reviews, or letters; (5) Studies that were non-clinical, such as animal or cell experiments.

2.3 Study Endpoints

The primary endpoint of our study was all-cause mortality at one year post-surgery. Secondary endpoints, also assessed at one-year post-surgery, included cardiac mortality, myocardial infarction, target lesion revascularization, target vessel revascularization, and stent thrombosis.

2.4 Data Extraction

Standardized data tables were utilized to extract baseline patient information and research data, including: (1) General information such as study type, first author, the study’s year and region, number of patients, age range, and sex distribution. (2) Past complications, including diabetes, insulin-dependent diabetes, hypertension, hyperlipidemia, smoking history, previous myocardial infarction, stable angina, unstable angina, and chronic renal failure. (3) Preoperative data such as left ventricular ejection fraction, which indicates heart function.

2.5 Quality Assessment

All included studies were RCTs. The quality assessment was conducted using the Cochrane quality assessment tool [27]. The assessment criteria included selection, implementation, measurement, follow-up, and other biases. Specifically, it assessed whether sequence generation was random, allocation concealment was preserved, blinding of participants and outcome assessors was implemented, data were complete and accounted for, there was selective reporting, and other potential biases. Each bias is categorized as “low risk”, “unclear risk”, or “high risk”. Additionally, we utilized the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology for evidence grading to assess the quality of evidence, including risk of bias, inconsistency, indirectness, imprecision, and publication bias, resulting in final grades of “high”, “moderate”, or “low” quality.

2.6 Statistical Analysis

Data analysis was conducted using Stata 17.0 software (Stata Corp LLC, College Station, TX, USA). For categorical variables, the odds ratio (OR) was utilized as the effect size, accompanied by a 95% confidence interval (CI). For continuous variables, the standard mean difference (SMD) was used as the effect size. Statistical significance was defined as a p-value of less than 0.05. The \chi² test, in combination with I² quantification, was used to assess heterogeneity. The significance level for the \chi² test was set at \alpha= 0.1. If significant heterogeneity was observed, indicated by an I² of \ge50% or a p-value 0.05, a random-effects model was applied for the meta-analysis. In cases where I² was 50% and the p-value was >0.05, a fixed-effects model was used. Sensitivity analysis was performed to assess the stability of the results. Subgroup analyses were conducted to further explore sources of heterogeneity. Publication bias was assessed using funnel plots and Egger’s test.

3. Results

3.1 Study Selection

A total of 3535 articles were initially retrieved, with an additional 6 obtained from other sources. After deduplication using EndNote 20.0 (Thomson ResearchSoft, Stanford, Connecticut, USA) and further manual processing, 2665 articles were included. Following the screening of titles and abstracts, 23 articles met the criteria. Following the full-text review, 13 articles were excluded for the following reasons: 2 were not RCTs, 6 were inaccessible in full-text, 2 did not report the outcomes of interest, and 3 exclude full text articles. Ultimately, 10 articles [13, 23, 28, 29, 30, 31, 32, 33, 34, 35], including a total of 1981 patients, were included in the analysis. The article screening process is illustrated in Fig. 1.

3.2 Research Characteristics and Quality Evaluation

All of the selected studies were RCTs published exclusively between 2014 and 2018. All studies were assessed using the Cochrane quality assessment tool, which determined that most outcome indicators are of medium to high quality, demonstrating a high level of credibility. Details of this assessment are shown in Fig. 2. Additionally, the GRADE system, which assesses the quality of evidence and strength of recommendations, classified most studies as medium to high quality. The classification details are provided in Table 1.

3.3 Patient Characteristics

The baseline characteristics of the patients included in this study are shown in Table 2 (Ref. [13, 23, 28, 29, 30, 31, 32, 33, 34, 35]). A total of 1981 ISR patients were treated with PCBs or EESs. The average age of the patients was 66.1 years, with a range of 64.0 to 69.6 years. The cohort comprised 63.0% males, although the percentage varied significantly across subgroups, ranging from 15.0% to 100%. Among the patients, 35.6% had diabetes, with the prevalence ranging from 4.0% to 50.0%. Of these, 14.3% had type 1 diabetes, with a range of 10.0% to 54.0%. Hypertension was present in 61.3% of the patients, with a prevalence range from 60.0% to 85.0%. Hyperlipidemia was reported in 69.4%, with a range of 52.0% to 96.0%. Additionally, 46.2% had a history of smoking (with a range of 12.0% to 75.0%), 51.6% had a history of myocardial infarction (ranging from 25.6% to 72.8%), 49.1% had stable angina (with a range of 26.5% to 68.0%), 44.2% had unstable angina (ranging from 20.0% to 52.0%), and 10.1% had chronic renal failure (with a range of 2.9% to 26.0%).

3.4 Meta-Analysis Results

3.4.1 One-Year All-Cause Mortality

Eight studies [13, 23, 30, 31, 32, 33, 34, 35] reported data on one-year all-cause mortality. Given the minimal heterogeneity observed among the studies (I² = 0.0%), a fixed-effect model was utilized for the meta-analysis. The results indicated no statistically significant difference in one-year mortality rates between the PCB group and the EES group (OR = 1.38, 95% CI (0.73–2.64), p = 0.322, I² = 0.0%). Details are illustrated in Fig. 3.

3.4.2 Cardiac Death

Seven studies [13, 23, 28, 30, 31, 33, 34] reported data on cardiac death. Given the negligible heterogeneity among these studies (I² = 0.0%), a fixed-effect model was utilized. The meta-analysis showed no statistically significant difference in cardiac death rates between the PCB group and the EES group (OR = 1.02, 95% CI (0.42–2.47), p = 0.963, I² = 0.0%). Further details are provided in Table 3 (Ref. [13, 23, 28, 29, 30, 31, 32, 33, 34, 35]).

3.4.3 Myocardial Infarction

A total of 10 studies [13, 23, 28, 29, 30, 31, 32, 33, 34, 35] reported on myocardial infarction. Due to the absence of significant heterogeneity among the studies (I² = 0.0%), a fixed-effect model was used for the meta-analysis. The meta-analysis revealed no statistically significant difference between the PCB-treated group and the EES-treated group (OR = 0.97, 95% CI (0.57–1.66), p = 0.915, I² = 0.0%). For further details, refer to Table 3.

3.4.4 Target Lesion Revascularization

We analyzed data from seven studies [23, 29, 30, 32, 33, 34, 35] on target lesion revascularization using a fixed-effect model, as heterogeneity among the studies was not significant (I² = 38.6%). The meta-analysis indicated a significantly higher probability of target lesion revascularization in the PCB group compared to the EES group (OR = 2.74, 95% CI (1.80–4.16), p 0.001, I² = 38.6%). Detailed results can be found in Table 3.

3.4.5 Target Vessel Revascularization

Nine studies [13, 23, 28, 29, 31, 32, 33, 34, 35] provided data on target vessel revascularization. Due to significant heterogeneity among the studies (I² = 56.9%), a random-effects model was used for analysis. The results indicated no statistically significant difference between the PCB and EES groups (OR = 1.14, 95% CI (0.65–2.02), p = 0.643, I² = 56.9%). Detailed findings are shown in Table 3.

3.4.6 Stent Thrombosis

Results related to stent thrombosis were reported by five studies [23, 28, 32, 33, 35]. Given the negligible heterogeneity among the studies (I² = 0.0%), a fixed-effect model was applied. The meta-analysis showed no statistically significant difference between the PCB group and the EES group (OR = 1.15, 95% CI (0.38–3.45), p = 0.800, I² = 0.0%). For further details, refer to Table 3.

3.5 Subgroup Analysis

Based on the cases of ISR, further analyses were conducted to explore sources of significant heterogeneity observed in certain outcome measures. These analyses were divided into two subgroups: Bare-metal stent-in-stent restenosis (BMS-ISR) and drug-eluting stent-in-stent restenosis (DES-ISR). The results of the one-year all-cause mortality subgroup analysis are as described below. The subgroup analyses of other secondary outcome measures were consistent with the overall results. For detailed results, refer to Table 3.

One-Year Overall Mortality Rate Subgroup Analysis Regarding ISR Causes

In the one-year mortality rate analysis, the BMS-ISR subgroup, which included three studies [31, 33, 35], was analyzed separately using a fixed effects model. This analysis revealed no statistically significant difference between the PCB group and the EES group (OR = 2.05, 95% CI (0.61–6.92), p = 0.245, I² = 0.0%). Similarly, the DES-ISR subgroup, which also comprised three studies [23, 30, 32], was analyzed separately using a fixed effects model. This analysis demonstrated no statistically significant difference between the PCB group and the EES group (OR = 1.00, 95% CI (0.35–2.89), p = 0.999, I² = 0.0%).

3.6 Sensitivity Analysis

Sensitivity analysis was performed by sequentially excluding individual studies. This approach confirmed that the results remained stable and showed no significant changes. The one-year all-cause mortality rate is illustrated in Fig. 4.

3.7 Bias in Published Results

We conducted a qualitative risk of bias assessment using funnel plots for all outcome indicators, and the results indicate that the funnel plots were symmetrical for each outcome. Fig. 5 illustrates the one-year all-cause mortality rate. Subsequently, we conducted a quantitative assessment of bias risk using Egger’s regression test. The one-year all-cause mortality rate is illustrated in Fig. 6. The results were as follows: One-year all-cause mortality rate (p = 0.579), Cardiogenic death (p = 0.081), Myocardial infarction (p = 0.403), Target lesion revascularization (p = 0.813), Target vessel revascularization (p = 0.236), Stent thrombosis (p = 0.668). These results suggest that there was no statistically significant publication bias across any of the measured outcomes.

4. Discussion

As PCI becomes more widely used, ISR has emerged as a major concern and limitation of the procedure [6, 8], drawing increasing attention in clinical practice. Moreover, as lesions become more complex, the incidence of restenosis is also rising. Research suggests that ISR is often a consequence of inevitable damage to the vascular intima during stent implantation, which triggers the proliferation of neointima. During this process, smooth muscle cells, facilitated by adhesion molecules, migrate to the injury site to form neointima [36, 37, 38] and secrete cytokines that further promote intimal proliferation [39]. These cytokines enhance the role of the smooth muscle cells in neointimal growth. Additionally, ISR may also be related to the formation of new atherosclerotic lesions. Studies have shown that the probability of detecting atherosclerosis increases during the later stages of ISR following stent implantation [40, 41, 42, 43]. This process is mainly characterized by the accumulation of foam cells (lipid-laden macrophages) around the stent, which subsequently leads to the formation of atheromatous plaques. The rupture of these plaques is a direct cause of ISR. Additionally, vascular damage triggers coagulation and enhances platelet activity, which not only promotes neointimal growth but also significantly raises the risk of thrombosis, potentially contributing to ISR. Currently, the optimal treatment method for ISR remains undetermined, with DES and DCB being the primary approach. EESs, a type of DES, are among the most commonly used and effective options, while paclitaxel is the most commonly used drug in DCB treatments. Although EESs are effective for treating various types of ISR [44], studies have shown that patients may still experience restenosis after treatment, and resistance to everolimus can impact its therapeutic effect. Furthermore, studies indicate that PCB treatments lead to significantly lower rates of late lumen loss compared to EES treatments. This is due to the absence of the need for repeated stent implantation [13, 45], which also improves their effectiveness in inhibiting neointimal proliferation. Given the optimal treatment method for ISR has not yet been determined [6, 7, 14, 15], it is essential to compare the efficacy of EES and DCB in treating ISR patients. Such comparisons will provide valuable insights for clinical practice.

A 2018 study by Alfonso et al. [23] indicated that the likelihood of requiring target lesion revascularization in ISR patients treated with PCB was significantly higher than in those treated with EES (OR = 3.16, p = 0.007). A 2014 study by Adriaenssens et al. [35] found no significant difference in the probability of myocardial infarction between ISR patients treated with either PCB or EES (OR = 0.33, p = 0.320). In 2018, a study by Baan et al. [31] also showed no significant difference in the probability of cardiogenic death between the ISR patients treated with either PCB or EES (OR = 0.34, p = 0.320). In 2020, Giacoppo D et al. [44] conducted a systematic review comparing the efficacy of DCB and DES in treating ISR patients. However, the DCB and DES included a wide variety of types, and no separate comparison was made between PCB and EES. In 2024, Guo S et al. [46] carried out a network meta-analysis comparing various treatment measures for ISR. However, the limitation was that when comparing PCB and EES, the selection of endpoint indicators was limited, and could not fully reflect the differences between the two treatment measures. These findings indicate inconsistent conclusions regarding the efficacy of PCB versus EES in treating ISR. Therefore, this study synthesizes past research to compare the efficacy differences of PCB and EES in treating ISR patients. The meta-analysis results show that in terms of target lesion revascularization, the likelihood of requiring this procedure was significantly greater in the PCB group compared to the EES group, consistent with previous findings [23, 34]. Potential contributing factors are: (1) For DES-ISR patients, there is an increased probability of neoatherosclerosis formation, and other potential factors may affect the demand for target lesion revascularization [23]. (2) There is a heterogeneous increase in fibrin deposition and loose connective tissue [47]. (3) The antiproliferative agents eluted from EES delay vascular healing [48]. In terms of one-year all-cause mortality, cardiogenic death, myocardial infarction, target lesion revascularization, and in-stent thrombosis, no significant differences were observed between the PCB group and the EES group, consistent with previous findings [28, 29]. This can be attributed to: (1) Both PCB and EES effectively preserved some endothelial functions within the vessels. (2) Both PCB and EES exhibited excellent anti-proliferative effects, preventing excessive neointimal hyperplasia. (3) Both PCB and EES reduced the risk of thrombosis formation.

Limitations of the Study

The study has the following limitations: (1) The comparison involved the PCB group with a single-layer strut and the EES group with a double-layer strut. This difference in strut could have influenced the outcome indicators. (2) The exclusion of highly complex ISR cases, including those with total occlusions, small vessels, or extensively diffuse disease may mean the generalizability of these findings to ISR patient populations with more complex coronary anatomies remains uncertain. (3) The study did not consider the impact of angiographic monitoring on revascularization rates. (4) These findings are only applicable to ISR patients who underwent sufficient pre-dilation before the procedure. (5) The exclusion of studies of a non-RCT design may have contributed to heterogeneity.

5. Conclusion

No significant differences were observed between the PCB and EES groups in terms of one-year all-cause mortality, myocardial infarction, and stent thrombosis; however, the PCB group required significantly more frequent revascularization of target lesions compared to the EES group. Therefore, it is recommended to preferentially use EES in the treatment of ISR for clinical decision-making. We sincerely hope that further studies regarding the long-term efficacy of EES versus PCB in the treatment of ISR will be carried out.

Availability of Data and Materials

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

References

[1] Cho YK, Nam CW. Percutaneous coronary intervention in patients with multi-vessel coronary artery disease: a focus on physiology. The Korean Journal of Internal Medicine. 2018; 33: 851–859. https://doi.org/10.3904/kjim.2018.006.

[2] Haji Aghajani M, Kobarfard F, Shojaei SP, Ahmadpour F, Safi O, Kazemina N, et al. The Impact of Clopidogrel Resistance on Clinical Outcome of Iranian Patients Undergoing Percutaneous Coronary Intervention. Iranian Journal of Pharmaceutical Research: IJPR. 2018; 17: 1099–1104.

[3] Pang Z, Zhao W, Yao Z. Cardioprotective Effects of Nicorandil on Coronary Heart Disease Patients Undergoing Elective Percutaneous Coronary Intervention. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 2017; 23: 2924–2930. https://doi.org/10.12659/msm.902324.

[4] García Del Blanco B, Hernández Hernández F, Rumoroso Cuevas JR, Trillo Nouche R. Spanish Cardiac Catheterization and Coronary Intervention Registry. 24th Official Report of the Spanish Society of Cardiology Working Group on Cardiac Catheterization and Interventional Cardiology (1990-2014). Revista Espanola De Cardiologia (English Ed.). 2015; 68: 1154–1164. https://doi.org/10.1016/j.rec.2015.09.002.

[5] Stefanini GG, Holmes DR Jr. Drug-eluting coronary-artery stents. The New England Journal of Medicine. 2013; 368: 254–265. https://doi.org/10.1056/NEJMra1210816.

[6] Alfonso F, Byrne RA, Rivero F, Kastrati A. Current treatment of in-stent restenosis. Journal of the American College of Cardiology. 2014; 63: 2659–2673. https://doi.org/10.1016/j.jacc.2014.02.545.

[7] Dangas GD, Claessen BE, Caixeta A, Sanidas EA, Mintz GS, Mehran R. In-stent restenosis in the drug-eluting stent era. Journal of the American College of Cardiology. 2010; 56: 1897–1907. https://doi.org/10.1016/j.jacc.2010.07.028.

[8] Kim MS, Dean LS. In-stent restenosis. Cardiovascular Therapeutics. 2011; 29: 190–198. https://doi.org/10.1111/j.1755-5922.2010.00155.x.

[9] Dibra A, Kastrati A, Mehilli J, Pache J, Schühlen H, von Beckerath N, et al. Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients. The New England Journal of Medicine. 2005; 353: 663–670. https://doi.org/10.1056/NEJMoa044372.

[10] Kastrati A, Mehilli J, von Beckerath N, Dibra A, Hausleiter J, Pache J, et al. Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial. JAMA. 2005; 293: 165–171. https://doi.org/10.1001/jama.293.2.165.

[11] Saia F, Lemos PA, Arampatzis CA, Hoye A, Degertekin M, Tanabe K, et al. Routine sirolimus eluting stent implantation for unselected in-stent restenosis: insights from the rapamycin eluting stent evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry. Heart (British Cardiac Society). 2004; 90: 1183–1188. https://doi.org/10.1136/hrt.2003.025536.

[12] Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D, et al. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial. JAMA. 2005; 294: 1215–1223. https://doi.org/10.1001/jama.294.10.1215.

[13] Claessen BE, Henriques JPS, Vendrik J, Boerlage-van Dijk K, van der Schaaf RJ, Meuwissen M, et al. Paclitaxel-eluting balloon versus everolimus-eluting stent in patients with diabetes mellitus and in-stent restenosis: Insights from the randomized DARE trial. Catheterization and Cardiovascular Interventions: Official Journal of the Society for Cardiac Angiography & Interventions. 2019; 93: 216–221. https://doi.org/10.1002/ccd.27814.

[14] Latib A, Mussardo M, Ielasi A, Tarsia G, Godino C, Al-Lamee R, et al. Long-term outcomes after the percutaneous treatment of drug-eluting stent restenosis. JACC. Cardiovascular Interventions. 2011; 4: 155–164. https://doi.org/10.1016/j.jcin.2010.09.027.

[15] Steinberg DH, Gaglia MA, Jr, Pinto Slottow TL, Roy P, Bonello L, De Labriolle A, et al. Outcome differences with the use of drug-eluting stents for the treatment of in-stent restenosis of bare-metal stents versus drug-eluting stents. The American Journal of Cardiology. 2009; 103: 491–495. https://doi.org/10.1016/j.amjcard.2008.09.107.

[16] Alfonso F, Fernandez C. Second-generation drug-eluting stents. Moving the field forward. Journal of the American College of Cardiology. 2011; 58: 26–29. https://doi.org/10.1016/j.jacc.2011.03.013.

[17] Alfonso F, Pérez-Vizcayno MJ, Cárdenas A, García del Blanco B, García-Touchard A, López-Minguéz JR, et al. A Prospective Randomized Trial of Drug-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With In-Stent Restenosis of Drug-Eluting Stents: The RIBS IV Randomized Clinical Trial. Journal of the American College of Cardiology. 2015; 66: 23–33. https://doi.org/10.1016/j.jacc.2015.04.063.

[18] Alfonso F, Pérez-Vizcayno MJ, Cárdenas A, García Del Blanco B, Seidelberger B, Iñiguez A, et al. A randomized comparison of drug-eluting balloon versus everolimus-eluting stent in patients with bare-metal stent-in-stent restenosis: the RIBS V Clinical Trial (Restenosis Intra-stent of Bare Metal Stents: paclitaxel-eluting balloon vs. everolimus-eluting stent). Journal of the American College of Cardiology. 2014; 63: 1378–1386. https://doi.org/10.1016/j.jacc.2013.12.006.

[19] Byrne RA, Neumann FJ, Mehilli J, Pinieck S, Wolff B, Tiroch K, et al. Paclitaxel-eluting balloons, paclitaxel-eluting stents, and balloon angioplasty in patients with restenosis after implantation of a drug-eluting stent (ISAR-DESIRE 3): a randomised, open-label trial. Lancet (London, England). 2013; 381: 461–467. https://doi.org/10.1016/S0140-6736(12)61964-3.

[20] Palmerini T, Biondi-Zoccai G, Della Riva D, Stettler C, Sangiorgi D, D’Ascenzo F, et al. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet (London, England). 2012; 379: 1393–1402. https://doi.org/10.1016/S0140-6736(12)60324-9.

[21] Authors/Task Force members, Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). European Heart Journal. 2014; 35: 2541–2619. https://doi.org/10.1093/eurheartj/ehu278.

[22] Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. The New England Journal of Medicine. 2007; 356: 998–1008. https://doi.org/10.1056/NEJMoa067193.

[23] Alfonso F, Pérez-Vizcayno MJ, Cuesta J, García Del Blanco B, García-Touchard A, López-Mínguez JR, et al. 3-Year Clinical Follow-Up of the RIBS IV Clinical Trial: A Prospective Randomized Study of Drug-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With In-Stent Restenosis in Coronary Arteries Previously Treated With Drug-Eluting Stents. JACC. Cardiovascular Interventions. 2018; 11: 981–991. https://doi.org/10.1016/j.jcin.2018.02.037.

[24] Scheller B, Hehrlein C, Bocksch W, Rutsch W, Haghi D, Dietz U, et al. Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. The New England Journal of Medicine. 2006; 355: 2113–2124. https://doi.org/10.1056/NEJMoa061254.

[25] Unverdorben M, Vallbracht C, Cremers B, Heuer H, Hengstenberg C, Maikowski C, et al. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Circulation. 2009; 119: 2986–2994. https://doi.org/10.1161/CIRCULATIONAHA.108.839282.

[26] Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine. 2009; 6: e1000097. https://doi.org/10.1371/journal.pmed.1000097.

[27] Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Clinical Research Ed.). 2011; 343: d5928. https://doi.org/10.1136/bmj.d5928.

[28] Pleva L, Kukla P, Zapletalova J, Hlinomaz O. Long-term outcomes after treatment of bare-metal stent restenosis with paclitaxel-coated balloon catheters or everolimus-eluting stents: 3-year follow-up of the TIS clinical study. Catheterization and Cardiovascular Interventions: Official Journal of the Society for Cardiac Angiography & Interventions. 2018; 92: E416–E424. https://doi.org/10.1002/ccd.27688.

[29] Wong YTA, Kang DY, Lee JB, Rha SW, Hong YJ, Shin ES, et al. Comparison of drug-eluting stents and drug-coated balloon for the treatment of drug-eluting coronary stent restenosis: A randomized RESTORE trial. American Heart Journal. 2018; 197: 35–42. https://doi.org/10.1016/j.ahj.2017.11.008.

[30] Moscarella E, Tanaka A, Ielasi A, Cortese B, Coscarelli S, De Angelis MC, et al. Bioresorbable vascular scaffold versus everolimus-eluting stents or drug eluting balloon for the treatment of coronary in-stent restenosis: 1-Year follow-up of a propensity score matching comparison (the BIORESOLVE-ISR Study). Catheterization and Cardiovascular Interventions: Official Journal of the Society for Cardiac Angiography & Interventions. 2018; 92: 668–677. https://doi.org/10.1002/ccd.27473.

[31] Baan J Jr, Claessen BE, Dijk KBV, Vendrik J, van der Schaaf RJ, Meuwissen M, et al. A Randomized Comparison of Paclitaxel-Eluting Balloon Versus Everolimus-Eluting Stent for the Treatment of Any In-Stent Restenosis: The DARE Trial. JACC. Cardiovascular Interventions. 2018; 11: 275–283. https://doi.org/10.1016/j.jcin.2017.10.024.

[32] Almalla M, Schröder J, Pross V, Marx N, Hoffmann R. Paclitaxel-eluting balloon versus everolimus-eluting stent for treatment of drug-eluting stent restenosis. Catheterization and Cardiovascular Interventions: Official Journal of the Society for Cardiac Angiography & Interventions. 2014; 83: 881–887. https://doi.org/10.1002/ccd.25072.

[33] Alfonso F, Pérez-Vizcayno MJ, García Del Blanco B, Otaegui I, Masotti M, Zueco J, et al. Long-Term Results of Everolimus-Eluting Stents Versus Drug-Eluting Balloons in Patients With Bare-Metal In-Stent Restenosis: 3-Year Follow-Up of the RIBS V Clinical Trial. JACC. Cardiovascular Interventions. 2016; 9: 1246–1255. https://doi.org/10.1016/j.jcin.2016.03.037.

[34] Alfonso F, Pérez-Vizcayno MJ, García Del Blanco B, García-Touchard A, Masotti M, López-Minguez JR, et al. Comparison of the Efficacy of Everolimus-Eluting Stents Versus Drug-Eluting Balloons in Patients With In-Stent Restenosis (from the RIBS IV and V Randomized Clinical Trials). The American Journal of Cardiology. 2016; 117: 546–554. https://doi.org/10.1016/j.amjcard.2015.11.042.

[35] Adriaenssens T, Dens J, Ughi G, Bennett J, Dubois C, Sinnaeve P, et al. Optical coherence tomography study of healing characteristics of paclitaxel-eluting balloons vs. everolimus-eluting stents for in-stent restenosis: the SEDUCE (Safety and Efficacy of a Drug elUting balloon in Coronary artery rEstenosis) randomised clinical trial. EuroIntervention: Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2014; 10: 439–448. https://doi.org/10.4244/EIJV10I4A77.

[36] Brancati MF, Burzotta F, Trani C, Leonzi O, Cuccia C, Crea F. Coronary stents and vascular response to implantation: literature review. Pragmatic and Observational Research. 2017; 8: 137–148. https://doi.org/10.2147/POR.S132439.

[37] Fujii K, Otsuji S, Yamamoto W, Takiuchi S, Ishibuchi K, Tamaru H, et al. Impact of optical coherence tomography-derived neointimal tissue morphology on development of very late in-stent restenosis. Catheterization and Cardiovascular Interventions: Official Journal of the Society for Cardiac Angiography & Interventions. 2020; 96: E398–E405. https://doi.org/10.1002/ccd.28799.

[38] Lekshmi KM, Che HL, Cho CS, Park IK. Drug- and Gene-eluting Stents for Preventing Coronary Restenosis. Chonnam Medical Journal. 2017; 53: 14–27. https://doi.org/10.4068/cmj.2017.53.1.14.

[39] Vengrenyuk Y, Nishi H, Long X, Ouimet M, Savji N, Martinez FO, et al. Cholesterol loading reprograms the microRNA-143/145-myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype. Arteriosclerosis, Thrombosis, and Vascular Biology. 2015; 35: 535–546. https://doi.org/10.1161/ATVBAHA.114.304029.

[40] Alfonso F, Restrepo J, Cuesta J, Bastante T, Rivero F, Benedicto A. Neoatherosclerosis causing edge in-stent restenosis: optical coherence tomography findings. Netherlands Heart Journal: Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. 2015; 23: 287–288. https://doi.org/10.1007/s12471-015-0680-y.

[41] Hong SJ, Lee SY, Hong MK. Clinical Implication of Optical Coherence Tomography-Based Neoatherosclerosis. Journal of Korean Medical Science. 2017; 32: 1056–1061. https://doi.org/10.3346/jkms.2017.32.7.1056.

[42] Nakamura D, Dohi T, Ishihara T, Kikuchi A, Mori N, Yokoi K, et al. Predictors and outcomes of neoatherosclerosis in patients with in-stent restenosis. EuroIntervention: Journal of EuroPCR in Collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2021; 17: 489–496. https://doi.org/10.4244/EIJ-D-20-00539.

[43] Otsuka F, Byrne RA, Yahagi K, Mori H, Ladich E, Fowler DR, et al. Neoatherosclerosis: overview of histopathologic findings and implications for intravascular imaging assessment. European Heart Journal. 2015; 36: 2147–2159. https://doi.org/10.1093/eurheartj/ehv205.

[44] Giacoppo D, Alfonso F, Xu B, Claessen BEPM, Adriaenssens T, Jensen C, et al. Drug-Coated Balloon Angioplasty Versus Drug-Eluting Stent Implantation in Patients With Coronary Stent Restenosis. Journal of the American College of Cardiology. 2020; 75: 2664–2678. https://doi.org/10.1016/j.jacc.2020.04.006.

[45] Pleva L, Kukla P, Kusnierova P, Zapletalova J, Hlinomaz O. Comparison of the Efficacy of Paclitaxel-Eluting Balloon Catheters and Everolimus-Eluting Stents in the Treatment of Coronary In-Stent Restenosis: The Treatment of In-Stent Restenosis Study. Circulation. Cardiovascular Interventions. 2016; 9: e003316. https://doi.org/10.1161/CIRCINTERVENTIONS.115.003316.

[46] Guo S, Bi C, Wang X, Lv T, Zhang Z, Chen X, et al. Comparative efficacy of interventional therapies and devices for coronary in-stent restenosis: A systematic review and network meta-analysis of randomized controlled trials. Heliyon. 2024; 10: e27521. https://doi.org/10.1016/j.heliyon.2024.e27521.

[47] Kim JS, Afari ME, Ha J, Tellez A, Milewski K, Conditt G, et al. Neointimal patterns obtained by optical coherence tomography correlate with specific histological components and neointimal proliferation in a swine model of restenosis. European Heart Journal. Cardiovascular Imaging. 2014; 15: 292–298. https://doi.org/10.1093/ehjci/jet162.

[48] Nusca A, Viscusi MM, Piccirillo F, De Filippis A, Nenna A, Spadaccio C, et al. In Stent Neo-Atherosclerosis: Pathophysiology, Clinical Implications, Prevention, and Therapeutic Approaches. Life (Basel, Switzerland). 2022; 12: 393. https://doi.org/10.3390/life12030393.

Funding

Natural Science Foundation of Gansu Province(24JRRA305)