Repeat drug-eluting stenting is superior to balloon angioplasty for prevention of recurrent in-stent restenosis (ISR), but carries a potential disadvantage of multiple layers of stent. The safety and effectiveness of a sirolimus drug-eluting balloon as an alternative has not been assessed.

The SELUTION4ISR trial is a prospective, multicenter, single-blinded, randomized, controlled trial. A total of 418 subjects with bare metal or drug-eluting stent (DES) ISR with up to 2 previous stent procedures at the target lesion, lesion length <26 mm and reference diameter ≥2.0 mm - ≤4.5 mm will be randomized 1:1 to treatment with either the SELUTION SLR™ DEB (SLR DEB) or standard of care (SOC), which includes either repeat DES or balloon angioplasty without drug coating. A subset of subjects will undergo planned angiographic and optical coherence tomography follow-up. The primary endpoint will be target lesion failure, defined as cardiac death, target vessel myocardial infarction, or clinically-driven target lesion revascularization at 12 months follow-up. The study will sequentially assess noninferiority of the SLR DEB to SOC in the overall cohort, followed by noninferiority then superiority of the SLR DEB to DES in the cohort with only 1 previous stent at the target lesion.

The trial is registered at Clinicaltrials.gov (NCT04280029).

The trial completed enrollment in July 2024.

The SELUTION4ISR study will evaluate the safety and effectiveness of SLR DEB in a prospective, randomized, international, multicenter trial for treatment of coronary ISR.

The optimal management strategy for in-stent restenosis (ISR) remains unclear. We aimed to determine the safety and efficacy of percutaneous coronary intervention with XIENCE cobalt chromium everolimus-eluting stents (EES) for treatment of ISR.

In the ILUMIEN IV (Optical Coherence Tomography Guided Coronary Stent Implantation Compared to Angiography: A Multicenter Randomized Trial in Percutaneous Coronary Intervention) trial, the 1-year outcomes of all randomized patients with a single diffuse or multifocal single-layer ISR lesion treated with EES were compared with a performance goal. The primary end point was target lesion failure, the composite of cardiac death, target vessel-myocardial infarction, or ischemia-driven target lesion revascularization. Outcomes in patients with a single EES-treated ISR and non-ISR lesion were also compared.

From May 2018 through December 2020, 247 patients with a single ISR lesion were treated with EES. Target lesion failure at 1 year occurred in 18 patients (7.4% [upper 1-sided 97.5% CI, 11.5%]), which was lower than the predefined performance goal of 20% (P<0.001). Compared with non-ISR lesions treated with EES (n=2021), the postpercutaneous coronary intervention minimal stent area by optical coherence tomography was smaller in treated ISR lesions (5.0±1.8 mm2 versus 5.6±1.9 mm2; P<0.001), but minimum stent expansion was similar (78.8±18.0% versus 79.0±16.9%; P=0.87), as was 1-year target lesion failure (7.4% versus 4.7%; hazard ratio, 1.58 [95% CI, 0.95-2.61]; P=0.07).

XIENCE EES was safe and effective for treatment of single-layer ISR. Compared with non-ISR lesions, ISR lesions treated with EES had a smaller postpercutaneous coronary intervention minimal stent area although stent expansion and 1-year target lesion failure rates were not different.

URL: https://clinicaltrials.gov/; Unique identifier: NCT03507777.

Stent failure (SF) is a complication of percutaneous coronary intervention (PCI).

This study aimed to assess the relationship of the optical coherence tomography (OCT) determined cause of SF with time since stent implantation, treatment, and outcome.

This retrospective study included patients who underwent an OCT evaluation for SF from January 2013 to July 2023. In-stent findings were evaluated on OCT including tissue proliferation, tissue type, underexpansion, thrombus, and multiple stent layers. The relationship between time to presentation, treatment, and outcome was assessed.

Of the 309 patients who underwent an OCT-guided PCI for SF, tissue proliferation was present in 228 (74%) and absent in 81 (26%). Among patients with tissue proliferation, OCT commonly showed lipidic neointima (n = 122, 54%), thrombus (n = 81, 36%), and underexpansion (n = 71, 31%). In patients without tissue proliferation, OCT commonly identified underexpansion (n = 58, 72%), thrombus (n = 55, 68%), and uncovered struts (n = 37, 46%). The mean time to SF was 6.89 ± 5.88 years with tissue proliferation and 2.98 ± 3.75 years without (p < 0.001). Patients with tissue proliferation were more likely to be treated with repeat stenting (78% vs. 60%, p < 0.001). Lipidic neointimal tissue and >1 layer of stent were predictors of target SF recurrence during a median 3 years of follow-up.

In a large series of OCT-guided treatments of SF, tissue proliferation was more common, occurred later after stent implantation, and was more likely to be treated with repeat stenting than no-tissue proliferation. Lipidic neointimal tissue and >1 layer of stent were significant predictors of target SF during follow-up.

The use of drug-coated balloons is a well-established strategy for the management of coronary vessels. However, head-to-head comparisons of sirolimus-coated balloons (SCBs) and paclitaxel-coated balloons (PCBs) for treating in-stent restenosis (ISR) are currently limited.

The aim of this randomized, controlled trial (SIBLINT-ISR [Sirolimus-Coated Balloon Versus Paclitaxel-Coated Balloon for the Treatment of Coronary In-Stent Restenosis]) was to compare a novel SCB with a PCB for the treatment of ISR.

In this prospective, assessor-blinded, controlled trial, patients with eligible ISR lesions were randomized 1:1 to treatment with either an SCB (SeQuent SCB, B. Braun Melsungen; 4 μg/mm2) or a PCB (SeQuent Please NEO, B. Braun Melsungen; 3 μg/mm2). The primary endpoint was noninferiority for 9-month angiographic in-segment late lumen loss (LLL). The main secondary endpoints were procedural success, target lesion restenosis rate, and target lesion failure (cardiac death, target vessel myocardial infarction, or revascularization) at 12 months.

A total of 258 patients with 285 lesions at 16 sites were randomly assigned to the SCB (n = 130) and PCB (n = 128) groups. At 9 months, the difference in the primary endpoint of in-segment LLL between the SCB group (0.37 ± 0.48 mm) and the PCB group (0.30 ± 0.38 mm) was 0.07 mm (95% CI: -0.05 to 0.19 mm), demonstrating noninferiority of the SCB to the PCB in terms of in-segment LLL, with a noninferiority margin of 0.20 mm (P for noninferiority < 0.0001). There were no significant differences in 12-month clinical outcomes between the SCB and PCB groups.

In this study, a novel SCB was found to be noninferior to a PCB in terms of in-segment LLL at 9 months in treating patients with ISR. (Sirolimus-Coated Balloon Versus Paclitaxel-Coated Balloon for the Treatment of Coronary In-Stent Restenosis [SIBLINT ISR]; NCT04240444).

Despite technical advances in percutaneous coronary intervention (PCI) and new iterations of drug-eluting stents (DES), complications still occur, including stent thrombosis and in-stent restenosis (ISR). Drug-coated balloons (DCBs) provide a promising option for the treatment of coronary lesions - particularly when DES are undesirable or contraindicated - allowing for PCI without the implantation of metallic devices, thus adhering to the 'leave nothing behind' principle.

A comprehensive literature search has been performed on PubMed, Web of Science and Cochrane, up to November 2024, with no significant restrictions. This article provides an overview of available DCB and summarizes the evidence supporting their use in different settings, including ISR, small-vessel disease, de novo large-vessel disease, and bifurcations.

Trials of DCB are heterogeneous with respect to population, sample size, follow-up, anatomical pattern, and device used. Furthermore, they usually have limited statistical power for clinical endpoints. Based on current knowledge, DES may be preferrable for DES-ISR, de novo lesions in large vessels and for the treatment of the main branch in true bifurcations, with DCB approved for small-vessel disease and selected ISR lesions. Ongoing trials are expected to provide definitive insights into the efficacy and safety of DCB in different scenarios.

Drug eluting stent (DES) could result in both in-stent restenosis and high bleeding risk due to long-term anti-platelet therapy. Drug-coated balloon (DCB) delivers anti-proliferative drugs without implanting metal into vascular wall. Our aim was to investigate its feasibility in large vessel coronary artery disease (LvCAD), compared to small vessel coronary artery disease (SvCAD).

This study enrolled 237 patients with de novo coronary lesions treated with DCB-only strategy and categorized according to the reference vessel diameter of 3 mm into SvCAD and LvCAD groups. The primary endpoint was in-lesion late lumen loss (LLL). The secondary endpoints included composite major adverse cardiac events (MACE), cardiac death, non-fatal myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and vessel thrombosis.

The immediate (3.06 ± 0.25 vs. 2.33 ± 0.21 mm, p = 0.001) and follow up minimal lumen diameter (3.13 ± 0.25 vs. 2.41 ± 0.21 mm, p = 0.001) and acute gain (1.92 ± 0.29 vs. 1.5 ± 0.26 mm, p = 0.04) were significantly higher in LvCAD group. In-lesion LLL was negative without significant difference (-0.07 ± 0.02 vs. - 0.06 ± 0.04 mm, p = 0.69). The incidence of adverse clinical events was not statistically significant accounting for 6.5 % vs. 10.5 % for composite MACE (p = 0.27), 0.8 % vs. 0.9 % for cardiac death (p = 0.96), 4.9 % vs.7 % for non-fatal MI (p = 0.49), 4.1 % vs. 6.1 % for TLR (p = 0.47), 2.4 % vs. 3.5 % for TVR (p = 0.63) and 1.6 % vs. 2.6 % for vessel thrombosis (p = 0.59).

DCB-only strategy is effective in treating LvCAD with comparable outcomes to SvCAD.

In recent years, drug-coated balloon (DCB) angioplasty has become an established treatment option for the treatment of coronary in-stent restenosis (ISR).

The aim of this study was to compare the angiographic and clinical performance of the Biolimus A9-coated balloon (BCB; Biosensors Europe) with that of the paclitaxel-coated balloon (PCB; SeQuent Please, Braun Melsungen).

REFORM (Prospective, Randomized, Non-Inferiority Trial to Determine the Safety and Efficacy of the Biolimus A9™ Drug Coated Balloon for the Treatment of In-Stent Restenosis: First-in-Man Trial) was a multicenter, assessor-blinded, noninferiority, 2:1 randomized controlled trial comparing the BCB and the PCB for the treatment of coronary ISR. The primary endpoint was in-segment percentage diameter stenosis at 6 months. Secondary endpoints included target lesion failure. The trial was registered prospectively at ClinicalTrials.gov (NCT04079192).

A total of 202 patients were randomized at 20 centers in 6 countries, with 135 in the BCB group and 67 in the PCB group. The mean patient age was 68.5 ± 10 years. At 6 months, in-segment percentage diameter stenosis was 43.3% ± 22.9% in the BCB group compared with 31.4% ± 17.7% in the PCB group (95% CI for the difference: 4.9%-18.8%; prespecified noninferiority margin 12%, noninferiority P = 0.48). At 1 year, target lesion failure was observed in 23.7% of patients in the BCB group vs 17.1% in the PCB group (HR: 1.44; 95% CI: 0.72-2.88; P = 0.28).

In patients with ISR, the REFORM study failed to demonstrate noninferiority of the investigational biolimus DCB compared with the standard paclitaxel DCB.

Drug-coated balloons present a potentially advantageous therapeutic approach for managing coronary in-stent restenosis (ISR). However, the comparative benefits of paclitaxel-coated balloons (PCBs) over uncoated balloons (UCBs) remain unclear.

We conducted a systematic review and meta-analysis to evaluate and compare the clinical outcomes of patients treated with PCBs and UCBs.

We systematically searched PubMed, Embase, and Cochrane for studies comparing PCBs and UCBs in managing coronary ISR. We used a random-effects model to pool risk ratios (RRs) and their 95% confidence intervals (CIs). Statistical analyses were conducted using Review Manager 5.4.1. Heterogeneity was assessed using I2 statistics. Quality and risk of bias were evaluated using the Cochrane Collaboration's tool.

We included seven randomized controlled trials with 1349 patients, of whom 840 underwent percutaneous coronary intervention with PCB. In our pooled analysis, patients treated with PCB had lower risks of target lesion revascularization (RR 0.31, 95% CI 0.18-0.52; p < 0.01), target vessel revascularization (0.53, 0.42-0.67; p < 0.01), major adverse cardiac events (MACEs) (0.25, 0.16-0.38; p < 0.01), and myocardial infarction (MI) (0.59, 0.37-0.95; p = 0.03). However, there were no significant differences in all-cause mortality (0.79, 0.37-1.70; p = 0.54), cardiac death (0.46, 0.03-8.12; p = 0.60), while tendencies for a significant difference were found for target lesion failure (0.39, 0.13-1.11; p = 0.08), or stent thrombosis (0.21, 0.03-1.35 p = 0.10).

These findings suggest that PCBs are superior to UCBs regarding the occurrence of target lesion revascularization, target vessel revascularization, MACEs, and MI, but they do not differ in all-cause mortality, and cardiac death, while trends to significant differences favoring PCB were found to stent thrombosis and target lesion failure.

Treatment of patients with in-stent restenosis (ISR) remains challenging. In this setting the use of drug-coated balloons (DCB) represents an attractive approach to avoid adding another metal layer to the coronary wall.

The Chansu Vascular Technologies (CVT)-ISR trial aimed to evaluate the safety and efficacy of a novel everolimus-DCB (CVT-DCB) using a new coating formulation and crystalline everolimus.

The CVT-ISR trial was a prospective, multicenter, open, single-arm, first-in-man (FIM) study. A total of 51 patients (mean age 69.2 years, 74.5% male) with single ISR coronary lesions (≤24 mm in length) were enrolled at nine sites in Europe.

The primary safety endpoint, freedom from target lesion failure (TLF) at 180 days, was 92.2%, with the lower bound of the 95% confidence interval (81.1%), above the protocol-defined objective performance criterion (OPC) (65% for conventional balloon angioplasty, P  < 0.05). At 1 year freedom from TLF was 90.2%. The primary efficacy endpoint, in-stent late lumen loss at 180 days (evaluated in a predefined subgroup of 25 patients scheduled for late angiography), was 0.40 mm (median 0.30 mm), lower than the protocol-defined OPC of the plain balloon angioplasty historical control (0.80 mm, P  < 0.001).

This FIM study demonstrated the superior efficacy of the new everolimus CVT-DCB compared with conventional balloon angioplasty in the treatment of patients with ISR.

NCT05731700.

Cardiovascular disease (CVD) claims millions of lives every year, with atherosclerotic cardiovascular disease (ASCVD) being the main cause. ASCVD treatment includes drug therapy, lifestyle intervention, and Percutaneous Coronary Intervention (PCI) all of which significantly enhance cardiovascular function and reduce mortality. However, hyperplasia can lead to vascular obstruction, worsen angina symptoms, or even cause heart disease, affecting patients' long-term prognosis. Therefore, finding effective ways to combat hyperplasia is crucial for cardiovascular therapy. In recent years, ferroptosis has gained attention as a new form of cell death closely associated with several diseases, including cardiovascular diseases. It involves complex metabolic processes critical for cellular homeostasis and normal function. Abnormal proliferation and phenotypic transformation of vascular smooth muscle cells (VSMC) are crucial mechanisms underlying cardiovascular disease development. Inhibiting ferroptosis in VSMC has the potential to significantly reduce neointima proliferation. Glucagon-like peptide-1 receptor agonist (GLP-1RA) constitutes a widely employed class of hypoglycemic agents with direct implications for the cardiovascular system, mitigating adverse cardiovascular events. Research indicates that the stimulation of GLP-1 holds promise as a therapeutic strategy in mitigating cardiovascular events such as restenosis. Hence, investigating the potential of GLP-1RA as a treatment option for cardiovascular ailments carries immense clinical significance.

Though superior to bare-metal stents (BMS), drug-eluting stents (DES) based PCI still have significant in-stent restenosis (ISR). Balloon angioplasty (BA), drug-coated balloons (DCBs), and DES are common modalities to treat ISR. The existing guidelines recommend treating ISR with either DCB or DES for BMS-ISR and DES-ISR, despite differences in the underlying mechanisms. Because DES are currently the most used stents worldwide, we performed a network meta-analysis (NMA) to compare DES-ISR treatment strategies.

We searched Cochrane Central Register of Controlled Trials, PubMed, Embase, and Scopus for relevant studies published until March 30, 2024 and performed a Bayesian NMA to synthesize direct and indirect evidence. The primary outcome was a target lesion revascularization (TLR) at follow-up.

Of 1202 studies, 30 were deemed eligible, with 15 being randomized studies. This included 8016 patients with DES-ISR who were assigned to 12 different PCI strategies. In the NMA for DES-ISR, paclitaxel-eluting stent (76.42) was the most effective strategy for TLR; paclitaxel-coated balloon (PCB) and scoring balloon angioplasty (75.88) for major adverse cardiovascular events (MACE); sirolimus-coated balloon (SCB) for target lesion failure (64.16), myocardial infarction (93.57), and stent thrombosis (98.53); and PCB for all-cause death (76.39) and cardiac death (83.74) based on SUCRA value. BA-based strategies were less effective alternatives for DES-ISR treatment with DCB or DES.

DES and DCB PCI such as PCB and SCB should be considered for treatment of coronary DES-ISR to achieve the most clinical efficacy and safety benefits for MACE. Further studies are required for more robust evidence on different treatment strategies.

Despite significant advancements in drug-eluting stent technology, in-stent restenosis (ISR) still occurs in approximately 10 % of patients undergoing percutaneous coronary intervention, remaining a significant global health concern. The mechanisms underlying ISR are complex and multifactorial, yet recent innovations in intravascular imaging and functional assessment have substantially advanced our understanding, enabling more targeted and personalized therapies. This review synthesizes the latest insights into ISR, emphasizing the pivotal roles of advanced imaging modalities, such as optical coherence tomography (OCT) and intravascular ultrasound, and functional assessments like quantitative flow ratio and optical flow ratio in guiding ISR management. Additionally, we explore the clinical implications of in-stent neoatherosclerosis and calcified nodules as key pathological mechanisms influencing restenosis progression and patient outcomes. The review also highlights the significance of OCT-based ISR classifications in refining treatment approaches. By integrating these diagnostic and therapeutic advances, this work provides clinicians and researchers with an updated foundation and actionable insights for optimizing ISR management through tailored, imaging-guided strategies.

Drug-eluting stent (DES) technology has greatly enhanced the safety and effectiveness of percutaneous coronary interventions (PCI). The aim of the present paper is to provide a comprehensive review of in-stent restenosis (ISR), focusing on the contemporary DES era, including its incidence, mechanisms, and imaging characterization.

Despite the widespread use of DES and numerous improvements, recent clinical data indicate that ISR still occurs in 5-10% of PCI procedures, posing a considerable public health issue. The incidence, morphology, and clinical implications of ISR are determined by a complex interplay of several factors: the patient, stent, procedure, and vessel and lesion-related factors. Advancements in intracoronary imaging have provided greater insight into its patterns and underlying causes. Over time, treatment strategies have evolved, and current guidelines recommend an individualized approach using intracoronary imaging to characterize ISR's underlying substrate.

Drug-coated balloon (DCB) angioplasty has emerged as an alternative to drug-eluting stent (DES) implantation for percutaneous coronary intervention (PCI) in patients with coronary in-stent restenosis (ISR) as well as de novo coronary artery disease.

DCBs are balloons coated with antiproliferative agents and excipients, whose aim is to foster favorable vessel healing after appropriate lesion preparation. By providing homogeneous antiproliferative drug delivery in the absence of permanent foreign body implantation, DCBs offer multiple advantages over DES, including preservation of vessel anatomy and function and positive vessel remodeling. As such, DCBs have become appealing for treatment of ISR, small-vessel disease, long lesions, simplification of bifurcation procedures, and treatment of diffuse distal disease after recanalization of chronic total occlusions. In addition, patients with high bleeding risk, diabetes, and acute coronary syndrome might also stand to benefit from DCB angioplasty.

Although commercially available in numerous countries now for more than a decade, DCB only recently obtained US Food and Drug Administration approval for the treatment of coronary ISR. Moreover, preliminary results from newer generation devices tested in different clinical scenarios have raised the interest of the international community. Accordingly, an up-to-date review is timely particularly with the anticipated wave of research on the matter. Herein, this review encompasses DCB technologies, their worldwide usage, details on relevant indications, and key procedural aspects of DCB angioplasty.

The study aims to explore the fluctuating expression of C/EBP Homologous Protein (CHOP) following rat carotid artery injury and its central role in vascular stenosis. Using in vivo rat carotid artery injury models and in vitro ischemia and hypoxia cell models employing human aortic endothelial cells (HAECs) and vascular smooth muscle cells (T/G HA-VSMCs), a comprehensive investigative framework was established. Histological analysis confirmed intimal hyperplasia in rat models. CHOP expression in vascular tissues was assessed using Western blot and immunohistochemical staining, and its presence in HAECs and T/G HA-VSMCs was determined through RT-PCR and Western blot. The study evaluated HAEC apoptosis, inflammatory cytokine secretion, cell proliferation, and T/G HA-VSMCs migration through Western blot, ELISA, CCK8, and Transwell migration assays. The rat carotid artery injury model revealed substantial fibrous plaque formation and vascular stenosis, resulting in an increased intimal area and plaque-to-lumen area ratio. Notably, CHOP is markedly elevated in vessels of the carotid artery injury model compared to normal vessels. Atorvastatin effectively mitigated vascular stenosis and suppresses CHOP protein expression. In HAECs, ischemia and hypoxia-induced CHOP upregulation, along with heightened TNFα, IL-6, caspase3, and caspase8 levels, while reducing cell proliferation. Atorvastatin demonstrated a dose-dependent suppression of CHOP expression in HAECs. Downregulation of CHOP or atorvastatin treatment led to reduced IL-6 and TNFα secretion, coupled with augmented cell proliferation. Similarly, ischemia and hypoxia conditions increased CHOP expression in T/G HA-VSMCs, which was concentration-dependently inhibited by atorvastatin. Furthermore, significantly increased MMP-9 and MMP-2 concentrations in the cell culture supernatant correlated with enhanced T/G HA-VSMCs migration. However, interventions targeting CHOP downregulation and atorvastatin usage curtailed MMP-9 and MMP-2 secretion and suppressed cell migration. In conclusion, CHOP plays a crucial role in endothelial injury, proliferation, and VSMCs migration during carotid artery injury, serving as a pivotal regulator in post-injury fibrous plaque formation and vascular remodeling. Statins emerge as protectors of endothelial cells, restraining VSMCs migration by modulating CHOP expression.

Drug-coated balloons have emerged as a promising therapeutic option in the treatment of cardiovascular disease. This review article provides an overview of the concept of drug-coated balloons and their clinical applications in both de novo and treated coronary artery disease. A summary of key clinical trials and registry studies evaluating drug-coated balloons is presented for reference. Overall, this article aims to provide clinicians and researchers with a comprehensive understanding of the current state of drug-coated balloon technology and its implications in clinical practice.

There is some evidence of a dose-response relationship for intravascular brachytherapy (IVBT) of native vessel or first-time in-stent restenosis (ISR). It has also been shown that in-field failure predominates following intravascular brachytherapy-treated lesions. Accordingly, it may be advantageous to increase the radiation dose(s) currently used. Given the rationale for escalation from currently doses, a scrutiny of the potential complications that have been reported seems timely.

PubMed was searched from 1966 through November 21st, 2023, using the terms coronary and brachytherapy, yielding 1287 references. A 10/16/24 follow-up search of Embase, using the terms "coronary and brachytherapy and complications", yielding 511 articles. In total, 68 articles were identified as adverse event reports based on their title, or by scrutinizing articles that did not mention adverse events in their titles.

The best documented adverse IVBT-related event is the occurrence of late (> 1 month) thrombosis. Following identification of the risk, longer DAPT regimens were adopted, bringing the incidence to non-IVBT levels. A variety of other adverse events have been reported, including aneurysms, dissections, arterial spasm, "black holes" and vasomotor response inhibition. However, none of which were associated with adverse clinical outcomes.

Nearly all reports regarding IVBT-related complications are retrospective analyses of a limited number of events, subject to reporting bias. Clinically important IVBT-related complications, at current doses, appear highly unlikely.

Despite the improvements in drug eluting stents (DES) technology, suboptimal results have been observed in certain higher-risk subsets of patients, as in diabetes mellitus (DM). Drug-coated balloons (DCB) could represent an alternative to DES in complex populations and anatomies, as in DM.

The present meta-analysis aimed at assessing the role of DCBs in patients with diabetes mellitus.

Studies comparing DCB versus percutaneous coronary revascularization (PCI) with/without DES for PCI in high-risk populations (>30% DM) were included. The primary efficacy endpoint was overall mortality, secondary endpoints were myocardial infarction, target lesion revascularization (TLR), and major adverse cardiovascular events (MACE).

We included 10 studies, comprising 2026 patients. Among them, 1002 patients (49.5%) were treated with DCB and 1024 with DES implantation. Among the included studies, 6 only enrolled diabetic patients and 2 had a prevalence of diabetes of 50%. At a mean follow-up of 15.3 months, mortality rate was 3.8% (82 patients), significantly lower with DCB (3.2% vs. 4.9% with DES; odds ratio [OR] [95% confidence interval {CI}] = 0.61 [0.38, 0.97], p = 0.04 phet = 0.34. A similar reduction in favor of DCB was observed for MACE (13.6% vs. 17.6%; OR [95% CI] = 0.79 [0.61, 1.04], p = 0.09, phet = 0.25), while TLR was significantly reduced only in the diabetic-restricted sub-analysis.

In the present meta-analysis, we showed a significant survival benefit and an absolute reduction in MACE and TLR with a DCB-based strategy as compared to DES in high-risk patients, mostly with DM. Future large-scale randomized trials, dedicated to this population, are deserved to confirm our findings.

Complex coronary anatomies and diabetes mellitus (DM) represent the pitfall of drug eluting stents (DES), mainly due to inflammatory and thrombotic complications, which should be reduced with drug-coated balloons (DCB).

We confirmed a significant advantage of DCB versus DES in the treatment of de novo lesions in high-risk patients and mainly in DM, reducing overall mortality, MACE and target lesion revascularization.

In-stent restenosis (ISR) remains the predominant cause of stent failure and the most common indication for repeat revascularization. Despite technological advances in stent design, ISR continues to pose significant challenges, contributing to increased morbidity and mortality among patients undergoing percutaneous coronary interventions. In the last decade, intravascular imaging has emerged as an important method for identifying the mechanisms behind ISR and guiding its treatment. Treatment options for ISR have expanded to include balloon angioplasty, cutting or scoring balloons, intravascular lithotripsy, atheroablative devices, drug-eluting stents, drug-coated balloons, surgical revascularization, and intravascular brachytherapy. The aim of the current review is to describe the classification and mechanisms of ISR, provide a comprehensive and updated overview of the evidence supporting different treatment strategies, suggest a management algorithm, and present insights into future developments in the field.

Drug-coated balloons (DCBs) offer an appealing therapeutic alternative for the treatment of patients with coronary in-stent restenosis (ISR). In-segment late lumen loss, translating into recurrent ISR and the clinical need for target lesion revascularization, represents a well-established and thoroughly investigated limitation of DCB in this setting. However, abrupt vessel occlusion, clinically presenting as ST-segment elevation myocardial infarction (STEMI), has not been previously described after DCB therapy for ISR.

We herein present the case of a 70-year-old patient that underwent percutaneous coronary intervention (PCI) with DCB for ISR. Despite achieving an excellent acute angiographic result (with no flow-limiting dissection and minimal angiographic residual stenosis), the patient presented 3 months later with STEMI due to occlusion of the previously treated segment. After adequate lesion preparation, a drug-eluting stent was implanted with optimal final angiographic result. The patient was discharged 2 days after the PCI without any post-procedural complications and remained asymptomatic at 6-month clinical follow-up.

This case report is the first description of an abrupt vessel occlusion presenting as STEMI following a DCB angioplasty for ISR. This exceptional presentation does not dismount the solid evidence supporting the long-term safety of DCB in these challenging patients.

Drug-coated balloon (DCB) angioplasty and drug-eluting stents (DES) are two widely used treatments for in-stent restenosis (ISR). Focal and non-focal types of ISR affect the clinical outcomes. The present study aims to compare DES reimplantation versus DCB angioplasty in acute coronary syndrome (ACS) patients with focal ISR and non-focal ISR lesions.

Patients with ISR lesions underwent percutaneous coronary intervention (PCI) were retrospectively evaluated and divided into DES group and DCB group. The primary endpoint was the incidence of target lesion failure (TLF) at 24 months follow up. Propensity score matching (PSM) was conducted to balance the baseline characteristics.

For focal ISR, TLF was comparable in the DES and DCB groups at 24 months of follow-up (Before PSM, hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.39-1.27; p = 0.244; After PSM, HR: 0.83; 95% CI: 0.40-1.73; p = 0.625). For non-focal ISR, TLF was significantly decreased in DES compared with DCB group (Before PSM, HR: 0.43; 95% CI: 0.29-0.63; p < 0.001; After PSM, HR: 0.33; 95% CI: 0.19-0.59; p < 0.001), which was mainly attributed to the lower incidence of clinically indicated target lesion revascularization (CD-TLR) (Before PSM, HR: 0.39; 95% CI: 0.26-0.59; p < 0.001; After PSM, HR: 0.28; 95% CI: 0.15-0.54; p < 0.001).

The clinical outcomes for DES and DCB treatment are similar in focal type of ISR lesions. For non-focal ISR, the treatment of DES showed a significant decrease in TLF which was mainly attributed to a lower incidence of CD-TLR.

In-stent restenosis (ISR) accounts for 10% of percutaneous coronary intervention (PCI) in the United States. Paclitaxel-coated balloons (PCBs) have been evaluated as a therapy for coronary ISR in multiple randomized controlled trials (RCTs). We searched PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov (from inception to April 1, 2024) for RCTs evaluating PCBs versus uncoated balloon angioplasty (BA) in patients with coronary ISR. The outcomes of interest were target lesion revascularization (TLR), major adverse cardiovascular events (MACEs), all-cause mortality, cardiovascular mortality, myocardial infarction (MI), and stent thrombosis. We pooled the estimates using an inverse variance random-effects model. The effect sizes were reported as risk ratio (RR) with 95% confidence interval (CI). A total of 6 RCTs with 1,343 patients were included. At a follow-up ranging from 6 to 12 months from randomization, the use of PCBs was associated with a statistically significant decrease in TLR (RR 0.28, 95% CI 0.11 to 0.68) and MACE (RR 0.35, 95% CI 0.20 to 0.64) compared with BA for coronary ISR. However, there was no significant difference in risk between PCBs and BA in terms of all-cause mortality (RR 0.56, 95% CI 0.14 to 2.31), cardiovascular mortality (RR 0.61, 95% CI 0.02 to 16.85), MI (RR 0.60, 95% CI 0.27 to 1.31), and stent thrombosis (RR 0.13, 95% CI 0.00 to 5.06). In conclusion, this meta-analysis suggests that PCBs compared with uncoated BA for the treatment of coronary ISR at intermediate-term follow-up of 1 year were associated with a significant decrease in TLR and MACE without any difference in mortality, MI, or stent thrombosis.

Drug-coated balloons (DCB) have promising results in the management of in-stent restenosis (ISR), still their role remains a major challenge, and not well established in contemporary clinical practice.

To provide a comprehensive appraisal of the efficacy and safety of DCBs in patients with in-stent restenosis (ISR).

We searched PubMed, Scopus, web of Science, Ovid, and Cochrane Central from inception until 30 March, 2023. We included randomized controlled trials (RCTs) that compared DCB versus DES in ISR patients. Our primary endpoints were major adverse cardiac events (MACE) and late lumen loss (LLL). Secondary clinical endpoints were all-cause death, cardiac death, MI, TLR, TVR, and stent thrombosis, and angiographic outcomes were MLD, and in-stent binary restenosis.

Ten RCTs comprising 1977 patients were included in this meta-analysis. The incidence of MACE was 15.57% in the DCB group compared to 14.13% in the DES group, with no significant difference in the risk of MACE following DCB (odds ratio [OR] 1.04, 95% confidence interval [CI]: 0.87 to 1.44). Compared with the DES intervention, the risk of LLL was comparable to the DCB intervention (mean difference [MD] -0.08, 95% CI: -0.18 to 0.02), while the incidence of TLR was increased in the DCB intervention (OR: 1.54, 95% CI: 1.2 to 1.99).

DCB was comparable to DES implantation is ISR patients regarding clinical outcomes, however it showed an increase in TLR events. Moreover, a RCT with large sample size and longer follow-up duration is warrened to validate these results.

Percutaneous coronary intervention (PCI) with drug-coated balloons (DCB) or drug-eluting stents (DES) are well-established treatments for in-stent restenosis, however little is known about the impact of vessel size on the outcomes. The study aimed to evaluate the efficacy and safety profile of DCB versus DES in DES in-stent restenosis depending on the vessel size.

Consecutive patients with DES in-stent restenosis who underwent PCI between January 2010 and February 2018 entered the registry with a long-term follow-up. Patients who received DCB at the index procedure were compared with those who received DES in three subgroups depending on the vessel size (≤2.5 mm; 2.5-3.5 mm; >3.5 mm). Data were analyzed using propensity score matching and Kaplan-Meier estimator plots.

Among 1,374 patients with DES in-stent restenosis, 615 were treated with DES and 759 with DCB. After propensity score matching, we analyzed 752 patients in the DES and DCB groups at a long-term follow-up. The risk of DOCE did not differ significantly between the DES and DCB groups, both in the overall population (HR 0.85; 95%CI [0.58; 1.26], log-rank p = 0.41) and when divided into small (HR 0.84; 95%CI [0.36; 1.95], log-rank p = 0.70), medium-sized (HR 0.90; 95%CI [0.49; 1.65], log-rank p = 0.73), and large-sized (HR 0.81; 95%CI [0.42; 1.53], log-rank p = 0.50) coronary arteries. The incidence of all-cause death was significantly higher in the overall DES population (HR 4.03; 95%CI [2.40; 6.79], log-rank p < 0.001) and subgroup of small (HR 5.54; 95%CI [1.80; 17.02], log-rank p = 0.003), medium-sized (HR 4.37; 95%CI [1.92; 9.94], log-rank p = 0.009) and large-sized coronary arteries (HR 3.26; 95%CI [1.35; 7.86], log-rank p = 0.02).

DES and DCB strategies are comparable methods of treating ISR regardless of the diameter of the treated vessel in a long-term follow-up.

The interventional treatment of coronary artery disease (CAD) has undergone significant improvements thanks to technological innovations. Nowadays, percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is the standard of care for the treatment of CAD. Nevertheless, the non-negligible incidence of in-stent restenosis (ISR) and suboptimal results in various anatomical settings has led to the development of drug-coated balloons (DCBs). DCBs are catheter-based balloons whose surface is coated with an anti-proliferative drug (mainly Paclitaxel or Sirolimus) loaded onto the balloon surface with different technologies and dose concentrations. In the beginning, these devices were used for the treatment of ISR showing an excellent efficacy profile in the inhibition of intimal hyperplasia. Subsequently, several studies evaluated their use in other angiographical and clinical contexts such as de novo lesions, small vessel disease, diffuse coronary disease, bifurcation lesions, acute coronary syndromes, high-bleeding risk and diabetic patients. This comprehensive review aims to describe the main DCB platforms on the market, their fields of application with the main supporting studies and their future perspectives.

This study aimed to compare the image quality and diagnostic performance of standard-resolution (SR) and ultra-high-resolution (UHR) coronary CT angiography (CCTA) based on photon-counting detector CT (PCD-CT) of coronary stents and explore the best reconstruction kernel for stent imaging.

From July 2023 to September 2023, patients were enrolled to undergo CCTA using a dual-source PCD-CT system after coronary angioplasty with stent placement. SR images with a slice thickness/increment of 0.6/0.4 mm were reconstructed using a vascular kernel (Bv48), while UHR images with a slice thickness/increment of 0.2/0.2 mm were reconstructed using vascular kernels of six sharpness levels (Bv48, Bv56, Bv60, Bv64, Bv72, and Bv76). The in-stent lumen diameters were evaluated. Subjective image quality was also evaluated by a 5-point Likert scale. Invasive coronary angiography was conducted in 12 patients (25 stents).

Sixty-nine patients (68.0 [61.0, 73.0] years, 46 males) with 131 stents were included. All UHR images had significantly larger in-stent lumen diameter than SR images (p < 0.001). Specifically, UHR-Bv72 and UHR-Bv76 for in-stent lumen diameter (2.17 [1.93, 2.63] mm versus 2.20 [1.93, 2.59] mm) ranked the two best kernels. The subjective analysis demonstrated that UHR-Bv72 images had the most pronounced effect on reducing blooming artifacts, showcasing in-stent lumen and stent demonstration, and diagnostic confidence (p < 0.001). Furthermore, SR and UHR-Bv72 images showed a diagnostic accuracy of 78.3% (95% confidence interval [CI]: 56.3%-92.5%) and 88.0% (95%CI: 68.8%-97.5%), respectively.

UHR CCTA by PCD-CT leads to significantly improved visualization and diagnostic performance of coronary stents, and Bv72 is the optimal reconstruction kernel showing the stent struts and in-stent lumen.

The significantly improved visualization of coronary stents using ultra-high resolution CCTA could increase the diagnostic accuracy for in-stent restenosis and avoid unnecessary invasive quantitative coronary angiography, thus changing the clinical management for patients after percutaneous coronary intervention.

Coronary stent imaging is challenging with energy-integrating detector CT due to "blooming artifacts." UHR images using a PCD-CT enhanced coronary stent visualization. UHR coronary stent imaging demonstrated improved diagnostic accuracy in clinical settings.

In-stent restenosis (ISR) is the gradual narrowing of the stented coronary segment, presenting as angina or leading to an acute myocardial infarction. Although its incidence has decreased with the use of newer drug-eluting stents (DES), it still carries significant mortality and morbidity risks. We compared the 2 most common interventions for managing DES-related ISR: drug-coated balloons (DCBs) and DES. Electronic databases were searched to identify all randomized controlled trials comparing DCB with DES in patients with DES-ISR. The Mantel-Haenszel method with a random-effects model was used to calculate pooled risk ratios. Five trials comprising 1,100 patients (577 in DCB and 523 in DES group) were included in the final study. The mean follow-up was 42 months. DCB was found to have a higher risk for target lesion revascularization (risk ratio 1.41, p = 0.02) compared with DES. No difference was observed in all-cause mortality, target vessel revascularization, myocardial infarction, or stroke between the 2 intervention arms. In conclusion, management of DES-ISR with DCB has a higher risk of target lesion revascularization compared with re-stenting with DES. The 2 therapeutic interventions are comparable in terms of efficacy and safety profile.

Drug-coated balloons (DCBs) are specialized coronary devices comprised of a semicompliant balloon catheter with an engineered coating that allows the delivery of antiproliferative agents locally to the vessel wall during percutaneous coronary intervention. Although DCBs were initially developed more than a decade ago, their potential in coronary interventions has recently sparked renewed interest, especially in the United States. Originally designed to overcome the limitations of conventional balloon angioplasty and stenting, they aim to match or even improve upon the outcomes of drug-eluting stents without leaving a permanent implant. Presently, in-stent restenosis is the condition with the most robust evidence supporting the use of DCBs. DCBs provide improved long-term vessel patency compared with conventional balloon angioplasty and may be comparable to drug-eluting stents without the need for an additional stent layer, supporting their use as a first-line therapy for in-stent restenosis. Beyond the treatment of in-stent restenosis, DCBs provide an additional tool for de novo lesions for a strategy that avoids a permanent metal scaffold, which may be especially useful for the management of technically challenging anatomies such as small vessels and bifurcations. DCBs might also be advantageous for patients with high bleeding risk due to the decreased necessity for extended antiplatelet therapy, and in patients with diabetes and patients with diffuse disease to minimize long-stented segments. Further studies are crucial to confirm these broader applications for DCBs and to further validate safety and efficacy.

In percutaneous coronary intervention (PCI) of de novo lesions, drug-coated balloons (DCB) have been shown to be a promising strategy to improve clinical outcomes of patients with small vessel disease. Evidence of this strategy in PCI of de novo coronary lesions in a real-world setting is limited. The objective of this study was to compare the 12-month outcomes of 2 paclitaxel-coated balloon systems for the treatment of all de novo coronary artery lesions.

All patients who were treated for de novo coronary artery stenosis with either SeQuent Please or In.Pact Falcon DCB at a single center from January 2014 to December 2018 were included. The primary end point was the composite of cardiac death, nonfatal myocardial infarction, and target vessel revascularization (3-point major adverse cardiovascular events) at 12 months.

A total of 496 patients with 623 lesions, of which 144 were treated with SeQuent Please and 352 were treated with In.Pact Falcon were included in the study. Baseline patient, lesion and procedural characteristics at baseline were similar between groups. At 12-month follow-up, 3-point major adverse cardiovascular event outcomes were similar (4.2% vs 2.3% respectively; P = .272). Deaths due to cardiovascular events were few and similar between groups (2.7% vs 1.1% respectively; P = .20).

Both paclitaxel DCB systems have similar efficacy and safety outcomes, suggesting that both may be an appropriate treatment choice for patients with de novo lesions. However, a larger randomized controlled study is needed to confirm these findings.

In-stent restenosis (ISR) remains the primary cause of target lesion failure following percutaneous coronary intervention (PCI), resulting in 10-year incidences of target lesion revascularization at a rate of approximately 20%. The treatment of ISR is challenging due to its inherent propensity for recurrence and varying susceptibility to available strategies, influenced by a complex interplay between clinical and lesion-specific conditions. Given the multiple mechanisms contributing to the development of ISR, proper identification of the underlying substrate, especially by using intravascular imaging, becomes pivotal as it can indicate distinct therapeutic requirements. Among standalone treatments, drug-coated balloon (DCB) angioplasty and drug-eluting stent (DES) implantation have been the most effective. The main advantage of a DCB-based approach is the avoidance of an additional metallic layer, which may otherwise enhance neointimal hyperplasia, provide the substratum for developing neoatherosclerosis, and expose the patient to a persistently higher risk of coronary ischemic events. On the other hand, target vessel scaffolding by DES implantation confers relevant mechanical advantages over DCB angioplasty, generally resulting in larger luminal gain, while drug elution from the stent surface ensures the inhibition of neointimal hyperplasia. Nevertheless, repeat stenting with DES also implies an additional permanent metallic layer that may reiterate and promote the mechanisms leading to ISR. Against this background, the selection of either DCB or DES on a patient- and lesion-specific basis as well as the implementation of adjuvant treatments, including cutting/scoring balloons, intravascular lithotripsy, and rotational atherectomy, hold the potential to improve the effectiveness of ISR treatment over time. In this review, we comprehensively assessed the available evidence from randomized trials to define contemporary interventional treatment of ISR and provide insights for future directions.

In-stent restenosis (ISR) has become a significant obstacle to interventional therapy for atherosclerotic cardiovascular disease. The optimal percutaneous coronary intervention (PCI) strategy for patients with coronary ISR remains controversial. This network meta-analysis (NMA) was aimed to compare and estimate the effectiveness of different PCI strategies and commercial devices for the treatment of patients with coronary ISR.

In present study, we systematically searched PubMed, Embase, Web of Science, and Cochrane Library from database inception to October 20, 2022, to identify randomized controlled trials. We included studies comparing various PCI strategies for the treatment of any type of coronary ISR. The study was registered with PROSPERO, CRD 42022364308.

We included 44 eligible trials including 8479 patients, 39 trials comparing the treatment effects of 10 PCIs, and 5 trials comparing the efficacy between different types of drug-eluting stent (DES) or drug-coated balloon (DCB) devices. Among the PCIs, everolimus-eluting stent was the optimal strategy considering target lesion revascularization (TLR), percent diameter stenosis (%DS), and binary restenosis (BR), and sirolimus-coated balloon was the optimal strategy considering late lumen loss (LLL). In the comparison of commercial devices, the combination strategy excimer laser coronary angioplasty plus SeQuent Please paclitaxel-coated balloon showed promising therapeutic prospects.

DCB and DES remain the preferred treatment strategies for coronary ISR, considering both the primary clinical outcome (TLR) and the angiographic outcomes (LLL, BR, %DS). Personalized combination interventions including DCB or DES hold promise as a novel potential treatment pattern for coronary ISR.