Author + information
- Received May 9, 2017
- Revision received June 22, 2017
- Accepted June 22, 2017
- Published online August 30, 2017.
- Fernando Alfonso, MDa,∗ (, )
- Javier Cuesta, MDa,
- María José Pérez-Vizcayno, MDb,c,
- Bruno García del Blanco, MDd,
- José Ramón Rumoroso, MDe,
- Francisco Bosa, MDf,
- Armando Pérez de Prado, MDg,
- Mónica Masotti, MDh,
- Raul Moreno, MDi,
- Angel Cequier, MDj,
- Hipólito Gutiérrez, MDk,
- Arturo García Touchard, MDl,
- José Ramón López-Mínguez, MDm,
- Javier Zueco, MDn,
- Vicens Martí, MDo,
- Maite Velázquez, MDp,
- César Morís, MDq,
- Teresa Bastante, MDa,
- Marcos García-Guimaraes, MDa,
- Fernando Rivero, MDa,
- Cristina Fernández, MDb,
- Interventional Cardiology Working Group of the Spanish Society of Cardiology
- aHospital Universitario de La Princesa, Madrid, Spain
- bHospital Universitario Clínico San Carlos, Madrid, Spain
- cFunación Interhospitalaria Investigación Cardiovascular, Madrid, Spain
- dHospital Universitario Vall d’Hebron, Barcelona, Spain
- eHospital de Galdakao, Vizcaya, Spain
- fHospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
- gHospital Universitario de León, León, Spain
- hHospital Universitario Clinic de Barcelona, Barcelona, Spain
- iHospital Universitario La Paz, Madrid, Spain
- jHospital Universitario de Bellvitge, Barcelona, Spain
- kHospital Universitario de Valladolid, Valladolid, Spain
- lHospital Universitario de Puerta de Hierro-Majadahonda, Madrid, Spain
- mHospital Universitario Infanta Cristina, Badajoz, Badajoz, Spain
- nHospital Universitario Marqués de Valdecilla, Santander, Spain
- oHospital Universitario San Pau, Barcelona, Spain
- pHospital Universitario 12 de Octubre, Madrid, Spain
- qHospital Universitario Central de Asturias, Oviedo, Spain
- ↵∗Address for correspondence:
Dr. Fernando Alfonso, Departamento de Cardiología, Hospital Universitario de La Princesa, Instituto Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, c/Diego de León 62, Madrid 28006, Spain.
Objectives This study sought to assess the value of bioresorbable vascular scaffolds (BVS) in patients with in-stent restenosis (ISR).
Background Currently both drug-eluting stents (DES) and drug-eluting balloons (DEB) are recommended in patients with ISR. However, the value of BVS in this setting remains unclear.
Methods RIBS VI was a prospective multicenter study (19 Spanish sites) that included 141 patients treated with BVS for either bare-metal stent (BMS) ISR or DES-ISR. Late angiography was scheduled at 6 to 9 months. Inclusion/exclusion criteria were similar to those used in the RIBS IV (patients with DES-ISR) and RIBS V (patients with BMS-ISR) trials, where DEB (249 patients) was compared with everolimus (EES)-DES (249 patients). Results of BVS in RIBS VI were compared with those obtained with DEB and EES in the RIBS IV and V trials.
Results On late angiography (134 patients; 95% of eligible) the in-segment minimal lumen diameter (primary endpoint) was 1.87 ± 0.5 mm, late lumen loss was 0.23 ± 0.4 mm, and restenosis rate was 11%. At 1-year follow-up (100% of patients) no patient died, 4 (2.8%) experienced a myocardial infarction, and 16 (11.3%) required target lesion revascularization. One patient (0.7%) who discontinued antiplatelet therapy experienced definitive BVS thrombosis. Freedom from cardiac death, myocardial infarction, and target lesion revascularization was 86%. The minimal lumen diameter at follow-up after BVS was similar to that obtained with DEB (1.88 ± 0.6 mm; p = NS) but smaller than that achieved after EES (2.16 ± 0.7 mm; p < 0.001). Likewise, target lesion revascularization rates after BVS were similar to those seen with DEB (10.4%) but higher than with EES (3.2%; p < 0.001). Results remained unchanged after adjusting for potential confounders in baseline characteristics.
Conclusions This study suggests the safety and efficacy of BVS in patients with ISR. In this challenging anatomic scenario BVS obtained late angiographic and clinical results similar to DEB but inferior to EES. (Restenosis Intrastent: Bioresorbable Vascular Scaffolds Treatment [RIBS VI]; NCT02672878)
Stent implantation represents the default strategy in patients undergoing percutaneous coronary interventions (1,2). Bare-metal stents (BMS) and drug-eluting stents (DES) are used in these procedures. BMS are still used, especially in patients with a perceived low risk of restenosis and those at high-bleeding risk or unable to maintain prolonged antiplatelet therapy. However, because of their drastic capacity to inhibit neointimal proliferation, DES are currently selected for most patients requiring coronary revascularization (1,2). Importantly, new-generation DES are not only safer but also more effective than first-generation DES (3). Nevertheless, even after the advent of new-generation DES, in-stent restenosis (ISR) remains a significant issue (4,5). Compared with BMS, DES significantly reduce the occurrence of ISR and the need for repeat revascularization, although these problems have not been completely eradicated, mainly because coronary interventions are being performed in increasingly complex clinical and anatomic scenarios (1,2). In the last decade the value of drug-eluting balloons (DEB) in patients with ISR has been established (6–8). Current guidelines suggest the use of DES or DEB in these patients (Recommendation I, level of evidence A) (1).
Recently, the value of bioresorbable vascular scaffolds (BVS) in patients with ISR has been advocated (9–12). The rationale behind this novel strategy is to benefit from the strong antiproliferative properties of these devices that, eventually, completely disappear from the vessel wall. Compared with DEB, BVS might be helpful in preventing early recoil. These issues are particularly attractive in patients with ISR because the implantation of another permanent metal layer can be avoided (9–12). Preliminary studies indicate that this strategy is safe and effective (9–16). However, previous studies assessing the value of BVS in patients with ISR were relatively small, retrospective in design, and did not include systematic late angiography (12–16).
In this prospective multicenter study with mandated late angiographic surveillance, we sought to assess the value of BVS in patients presenting with ISR. In addition, we selected identical inclusion/exclusion criteria and the same methodology to that used in previous RIBS (Restenosis Intra-stent: drug-eluting Balloon vs everolimus-eluting Stent) studies (17,18) to be able to ascertain the relative value of BVS compared with DES and DEB in this challenging anatomic scenario.
From April 2014 to December 2015 a total of 141 consecutive patients from 19 Spanish University centers, presenting with either BMS-ISR or DES-ISR, were prospectively enrolled in the RIBS VI study. Inclusion and exclusion criteria were similar to those in previous RIBS randomized trials (17,18). Namely, patients with angina or objective evidence of ischemia presenting with ISR (>50% diameter stenosis on visual assessment) were eligible. Patients with very long lesions (>32 mm in length) or small vessels (<2.5 mm in diameter) were excluded. Patients with a stent implanted very recently (<1 month), those with angiographic evidence or intracoronary thrombus or totally occluded vessels were also excluded. However, patients with multiple previous interventions (including stents) in the target lesions were eligible. Likewise, patients with edge-ISR were included when the stent edge was involved (intracoronary imaging was recommended in unclear cases). Patients with allergy to aspirin or thienopriridines and those with severe life-threatening conditions with a life expectancy <1 year were not included. Patients with severe renal failure, extensive peripheral arterial vascular disease, or other anticipated problems for the mandated late angiographic evaluation were also excluded (17,18).
RIBS VI was an independent, investigators-driven initiative developed within the RIBS program under the auspices of Working Group on Interventional Cardiology of the Spanish Society of Cardiology. The Hospital Universitario de La Princesa in Madrid was the coordinating center and the Spanish Society of Cardiology was the study promoter. An unrestricted research grant was obtained from Abbott Vascular. Written informed consent was obtained in all patients. The study protocol was approved by the ethics committees of the corresponding institutions (Online Appendix). The primary angiographic endpoint was the in-segment minimal lumen diameter at late angiographic follow-up.
The RIBS-V (Restenosis Intra-stent of bare-metal stents: drug-eluting Balloon vs everolimus-eluting Stent; NCT01239953) study compared DEB with everolimus-eluting stents (EES) in patients with BMS-ISR (17). The RIBS-IV (Restenosis Intra-stent of drug-eluting stents: drug-eluting Balloon vs everolimus-eluting Stent; NCT01239940) study compared DEB with EES in patients with DES-ISR (18). RIBS V allocated 189 patients with BMS-ISR to either DEB (n = 95) or EES (n = 94) (17). RIBS IV allocated 309 patients with DES-ISR to either DEB (n = 154) or EES (n = 155) (18). The comparison of the results of RIBS VI with those previously obtained in RIBS IV and V was predefined in the study protocol (Figure 1).
The protocol for coronary interventions was similar to that used in previous RIBS trials (17,18). Briefly, patients were pretreated with aspirin and thienopiridines and during interventions received intravenous heparin targeting for an activated clotting time >250 s. Special care was taken to ensure optimal lesion pre-dilation before BVS implantation. In this regard major care was taken to treat the entire lesion length but avoid damaging the adjacent normal coronary segments. By protocol underexpanded stents were aggressively tackled with noncompliant balloons at very high pressures (17,18). As recommended, BVS were deployed slowly (progressive increments in pressure every 10 s) to completely cover the ISR lesion plus the injured segment. Post-dilation with high-pressure and noncompliant balloons was recommended but the use of balloons >0.5 mm larger than the nominal diameter of the selected BVS was discouraged. A liberal use of intracoronary imaging was recommended, although the use of imaging was left at the discretion of the operator.
In all patients serial assessment of cardiac enzymes (creatine-kinase levels [with MB fraction when abnormal], and troponins) and 12-lead electrocardiograms were obtained after the procedure (17,18). Dual antiplatelet therapy was recommended for 1 year.
Late angiographic assessment was scheduled at 6 to 9 months or earlier if clinically indicated. The same electronic case report forms and database of previous RIBS trials were used (17,18). An independent and blinded Clinical Event Committee adjudicated all adverse events after carefully reviewing the anonymized source documents. All patients were scheduled for late clinical follow-up; patients not coming back to the outpatient clinics were contacted by telephone using a structured questionnaire. Deaths were considered as cardiac unless a definitive noncardiac cause could be established. The diagnosis of myocardial infarction was based on the same definition used in previous RIBS trials (17,18). Namely: 1) prolonged (>30 minutes) chest pain; 2) typical rise and fall in creatine-kinase levels (more than twice normal values, with elevated MB fraction); and 3) development of ischemic electrocardiogram changes (with or without new pathological Q waves) (17,18). By protocol all revascularization procedures during follow-up had to be clinically indicated (angina, noninvasive objective documentation ischemia, or abnormal [<0.80] fractional flow reserve). The angiograms of all patients undergoing revascularization during follow-up were carefully reviewed centrally to determine the exact location of the repeated intervention. Stent thrombosis was classified using the Academic Research Consortium definition (19).
Coronary angiograms were analyzed by trained personnel in a centralized core-laboratory using a systematic methodology (17,18). ISR angiographic patterns were characterized using the Mehran et al. (20) and the American College of Cardiology/American Heart Association (21) classifications. Carefully selected, orthogonal projections (free from major overlapping side-branches and significant vessel foreshortening) were obtained following intracoronary nitroglycerin administration before, immediately after intervention, and at late follow-up. A validated edge-detection system was used for quantitative coronary angiography (CAAS II System, Pie Medical, Maastricht, The Netherlands) (17,18). All analyses encompassed in-lesion and in-segment (initial lesion + injured segment + 5 mm margins) measurements.
Continuous data are presented as mean ± SD or median (25th to 75th percentile) as required after using the Kolmogorov-Smirnov test to assess normality. Continuous data were compared with the Student t test or the Wilcoxon rank-sum test as required. Categorical data are presented as counts and (%) and compared with the Pearson chi-square test or Fisher exact test. The potential influence of 10 pre-specified clinical and anatomic subsets on the primary angiographic endpoint (in-segment minimal lumen diameter at follow-up) was analyzed (17,18). Event-free survival after different interventions was estimated using Kaplan-Meier curves compared using the log-rank and Berslow exact tests. Multivariate linear mixed regression models adjusting for center, and Cox proportional hazards regression analyses, were performed to adjust for potential confounders in baseline characteristics among therapies in the different RIBS trials. All variables with differences (p < 0.1) at univariate analysis were entered in a backward stepwise model after excluding collinearity (center, age, diabetes, smoking, time to ISR, >1 intervention in target lesion, type of underlying stent [BMS vs. DES], lesion length, baseline minimal lumen diameter, % diameter stenosis, inflation time, and final pressure). Crude and adjusted risk ratio and hazard ratio (HR; 95% confidence interval [CI]) were obtained from exacts calculations from STATA. The SPSS (SPSS, Chicago, Illinois) version 15.00 statistical package was used. A p value <0.05 was considered as statistically significant.
Baseline clinical and angiographic characteristics of patients treated with BVS for ISR are presented in Table 1. Mean age was 65 years and 11% of patients were female. Importantly, one-half of the patients had diabetes mellitus and most patients presented relatively late after the initial intervention (Table 1). A total of 51% of patients had DES-ISR and 15% of them had required >1 intervention on the target lesion. A total of 50% of lesions had a diffuse pattern and 15% were edge-ISR. Before BVS implantation pre-dilation was performed in 97% of patients (mean pressure, 17.1 ± 4.5 bar), whereas post-dilation was performed in 66% of patients (mean pressure, 19.2 ± 5.1 bar). Angiographic success was obtained in all patients. For comparison, data from patients treated with DEB and EES in the RIBS IV and V trials are also presented (Table 1) (17,18).
Qualitative and quantitative angiographic findings of BVS in RIBS VI and of DEB and EES in RIBS IV and V trials are summarized in Table 2. Immediately after the procedure BVS results were similar to those of DEB but poorer than those of EES both in the in-segment and in-lesion analyses. This was mainly a result of the larger acute gain achieved with EES compared with BVS and DEB. Angiographic follow-up of RIBS VI was obtained in 134 patients (95% of those eligible) similar to that achieved in previous RIBS studies. After BVS the in-segment minimal lumen diameter at follow-up (primary endpoint of the study) was 1.87 ± 05 mm, late lumen loss was 0.23 ± 0.4 mm, and binary restenosis rate was 11%. Interestingly, late angiographic findings of BVS and DEB were very similar (Table 2, Figures 2 and 3). However, late angiographic results of EES (including minimal lumen diameter, percent diameter stenosis, late lumen loss, and binary restenosis rate) were significantly better than those obtained with BVS and DEB (Table 2, Figures 2 and 3). Importantly, after adjusting for differences in baseline characteristics and center, the minimal lumen diameter at follow-up after EES remained significantly larger than that observed after BVS (adjusted absolute mean difference, 0.32 mm; 95% CI: 0.11 to 0.46; p < 0.0001) whereas the results of BVS and DEB remained similar (adjusted absolute mean difference, 0.09 mm; 95% CI: −0.07 to 0.24; p = 0.28). The results of the primary endpoint (presented as differences in absolute in-segment minimal lumen diameter at follow-up) were relatively uniform and consistent across several pre-defined clinical and angiographic characteristics (Figure 4). After formal testing the only significant interaction among these therapies was in relation to the underlying stent (BMS-ISR vs. DES-ISR) in the BVS versus EES comparison (p for interaction = 0.027) (Figure 4).
Clinical results at 1 year were obtained in 100% of patients treated with BVS in RIBS VI (Table 3). At late follow-up, no patient died, 4 (2.8%) experienced a myocardial infarction, and 16 (11.3%) required target lesion revascularization. Of note, all patients undergoing revascularization at follow-up had angina or objective evidence of ischemia. One patient who voluntarily discontinued antiplatelet therapy 3 months after the intervention experienced a large anterior myocardial infarction as a result of definitive BVS thrombosis. Event-free survival, freedom from cardiac death, myocardial infarction, and target lesion revascularization at 1 year, was 86%. Clinical results of BVS were very similar to those obtained with DEB (Table 3, Figures 5 and 6). However, EES provided better clinical outcomes than either BVS or DEB, mainly because of a reduction in the need for target lesion revascularization (Table 3, Figures 5 and 6). Importantly, after adjusting for differences in baseline characteristics, target lesion revascularization (adjusted HR: 0.24; 95% CI: 0.09 to 0.66; p = 0.006), target vessel revascularization (adjusted HR: 0.38; 95% CI: 0.17 to 0.83; p = 0.015), and the combined clinical outcome measure (cardiac death, myocardial infarction and target lesion revascularization) (adjusted HR: 0.43; 95% CI: 0.19 to 0.93; p = 0.03) were significantly reduced with EES compared with BVS, whereas no differences were found in these outcome measures between BVS and DEB (adjusted HR: 0.62; 95% CI: 0.29 to 1.32; p = 0.22) (adjusted HR: 0.66; 0.33 to 1.30; p = 0.23) (adjusted HR: 0.71; 95% CI: 0.36 to 1.40; p = 0.32), respectively.
There are several main findings of this prospective multicenter study. First, BVS seem to represent a safe novel therapeutic strategy for patients with ISR. Importantly, in this study procedural success was obtained in all patients. The systematic use of an adequate pre-dilation strategy seems to be of major value to ensure a successful BVS implantation in this scenario. The only single patient that experienced a late BVS thrombosis had prematurely discontinued the required dual antiplatelet therapy. This supports the safety of this strategy but also reinforces the relevance of ensuring adequate therapeutic counselling after BVS implantation. Second, BVS constitute an effective new therapeutic modality in this challenging anatomic setting. Clinical recurrences only occurred in 11.3% of patients that required target lesion revascularization during follow-up. Third, late angiographic findings after BVS implantation were favorable. This is of interest because the 6- to 9-month time frame used to obtain the late angiographic follow-up was selected before complete reabsorption of the BVS was expected to occur. Therefore, it remains possible that angiographic findings might eventually improve later on following complete BVS disappearance. However, this issue remains completely speculative and further studies are required to elucidate this intriguing possibility.
Fourth, BVS seem to be equally effective for patients with BMS-ISR and DES-ISR. This is in contradistinction with some previous studies suggesting a poorer outcome after interventions in patients with DES-ISR than in those with BMS-ISR (5). Nevertheless, because of the relatively small sample size major caution is required during the interpretation of these findings. Fifth, in patients with ISR the results obtained with BVS are very similar to those achieved with DEB according to the pre-specified comparison with previous RIBS trials. Indeed, most late angiographic parameters and target lesion revascularization rates were very similar with the 2 strategies. Moreover, the late angiographic and clinical results remained also similar after adjusting for the differences in baseline characteristics. This is of major relevance because currently clinical practice guidelines recommend DEB as a first-line therapy for these patients (1). However, further studies with longer clinical follow-up are required to definitively establish the relative efficacy of these interventions that do not required implantation of an additional metal layer (leave nothing behind strategies). Finally, the angiographic and clinical results of BVS seem to be inferior to those obtained with EES. Notably, the angiographic and clinical superiority of the EES over BVS remained statistically significant after carefully adjusting for potential confounders.
Previous studies of BVS in patients with ISR
Information on the safety and efficacy of BVS in patients with ISR is scarce. Some case reports and preliminary small series suggested the potential value of BVS in these patients (9–12). In a pilot study we used optical coherence tomography to guide BVS implantation in 15 consecutive patients with ISR (12). In these patients the use of this imaging technique proved to be of help to optimize BVS results. In this small series, however, a patient with suboptimal initial result, caused by severe resistant underexpansion, experienced a subacute BVS thrombosis (12). A 2-center Italian registry reported results in 27 patients with ISR (31 lesions) treated with BVS (13). A diffuse pattern of ISR was found in 70% of cases. Procedural success was obtained in all patients. At 1-year follow-up, 1 patient died of noncardiac causes, another from possible BVS thrombosis, and 3 patients (11.1%) required target vessel revascularization (13). In addition, Jamshidi et al. (14) reported the use of BVS in a single-center observational series including 65 patients with 84 ISR lesions (94% DES-ISR). Procedural success was achieved in all patients. Interestingly, although post-dilation was only performed in one-half of the patients, when this strategy was selected very high pressures (mean, 27 bar) were used. Clinical follow-up was obtained in all patients at 6 months and in 49 patients (75%) at 1 year. During this time period 2 patients died from noncardiac causes and another developed a myocardial infarction but no patient experienced BVS thrombosis. Rates of target lesion revascularization at 6 and 12 months were 3.1% and 12.1%, respectively (14). Of interest, in this series all patients requiring repeat target vessel revascularization initially presented with adverse (proliferative or occlusive) ISR patterns (14). Finally, another recent multicenter Italian study (15,16) included 116 patients (127 ISR lesions) treated with BVS. Most lesions were DES-ISR and had a diffuse angiographic pattern. Procedural success was achieved in all patients. At 15-month follow-up, the incidence of the device-oriented composite endpoint (cardiac death, target-vessel myocardial infarction, and ischemia-driven target lesion revascularization) was 9.1%, with no differences between patients presenting with DES-ISR (10.9%) and BMS-ISR (6.4%) (15,16). Overall, 9 patients (7.6%) required target vessel revascularization for ischemia, 3 (2.7%) developed a myocardial infarction (only 1 target vessel–related myocardial infarction), 2 patients experienced a definitive/probable BVS thrombosis, and 4 patients (3.3%) died (3 cardiac deaths) (15,16). This relatively large study is of clinical interest, although only patients selected to be treated with BVS during the study period were included. In addition, events were site-reported and not adjudicated by a central clinical events committee (16). Finally, systematic late angiographic surveillance was not obtained in any of these previous studies, thus the information on the efficacy of this strategy remains limited (12–16).
Further insights and clinical implications
This is the first prospective study assessing the value of BVS in patients with ISR that includes systematic angiographic surveillance. In addition, because the same methodology of previous RIBS studies was selected (17,18) and appropriate adjustments for potential confounders were performed, the current study provides novel unique insights on the relative value of BVS compared with DEB and EES in this scenario. This is of major relevance because both DEB and EES currently represent the recommended strategies for these patients (1).
Treatment of patients with DES-ISR is more challenging than treatment of patients with BMS-ISR (3,4). In patients with BMS-ISR the RIBS V randomized study (18) demonstrated that EES provide superior late angiographic results compared with DEB. Although clinical outcomes at 1 year were similar with the 2 strategies, a marginal benefit regarding target lesion revascularization in favor of EES was found at 3 years (22). However, in patients with DES-ISR, the RIBS IV randomized study demonstrated the superiority of EES compared with DEB regarding both late angiographic findings and long-term clinical outcomes.
Our current findings suggest the feasibility, safety, and efficacy of BVS in patients with ISR. This novel strategy provides satisfactory late clinical and angiographic results in these patients. Our findings also suggest that BVS are equivalent to DEB with regard to 1-year clinical and angiographic outcomes. Notably, both strategies avoid the need for implanting an additional permanent metal layer (“leave nothing behind” strategies). Our findings also indicate that EES remain superior to BVS regarding late angiographic findings and also 1-year clinical outcomes. The difference was mainly driven by a reduced need of target lesion revascularization after EES. The larger acute gain and the smaller late loss obtained with EES seem to account for the superiority of this strategy. However, randomized head-to-head studies are required to confirm the relative value of these therapeutic modalities in patients with ISR.
It is important to keep in mind that in patients with de novo lesions several randomized clinical trials comparing BVS with EES initially yield similar results. However, the extended follow-up of these trials, together with information gathered by recent meta-analyses, suggested that BVS are indeed associated with a small, yet significant, higher risk of stent thrombosis (23–25). Late structural deterioration of the BVS might occasionally obstruct the lumen. In addition, these studies also suggested that acute and late angiographic findings were superior with EES compared with BVS. Our findings comparing BVS with EES in an ISR anatomic substrate seem to be largely concordant with the results previously seen in de novo lesions. Nevertheless, in patients with ISR the use of multiple additional metal layers does not represent a particularly attractive strategy (5). Therefore, DEB or BVS may be considered not only adequate, but also as attractive alternatives for selected patients with ISR. The evidence supporting the efficacy of DEB in this scenario is overwhelming (1,6–8,17,18), whereas the available information on the value of BVS in patients with ISR still remains limited (12–16). Importantly, in de novo lesions BVS seem to be less effective in small vessels (12–16). This problem might be of particular concern in patients with ISR, frequently with small vessels, where the problem of strut “overcrowding” may be facilitated by the size of current BVS struts. However, by protocol, small vessels were excluded from our study and adequate pre- and post-dilation was recommended. In addition, very diffuse ISR were not included in RIBS VI. Again, because of the strut size, overlapping BVS would seem as less attractive than overlapping EES or DEB treatment in these patients, but additional studies are required to address this issue. These technical considerations, however, should be kept in mind when BVS are considered for the treatment of patients with ISR.
First, RIBS VI was not a randomized trial and its size was relatively small. Nevertheless, this remains the largest study assessing the value of BVS in patients with ISR. In addition, although we used similar inclusion/exclusion criteria, methodology of analysis, and selected the same sites involved in prior RIBS trials, the possibility of selection bias cannot be completely excluded. Likewise, despite careful adjustment for baseline characteristics, the comparison of BVS with EES and DEB in previous RIBS trials (17,18) may be limited by the presence of unmeasured confounders. Besides, the study is largely unpowered for subgroup analyses and for the assessment of most individual endpoints. Larger studies with a longer clinical follow-up are required to definitively establish the role of BVS in patients with ISR. In particular, the concerns regarding a potential increased risk of very-late (>1 year) thrombosis after BVS implantation in this complex scenario should be dissipated in further studies. Finally, only randomized head-to-head studies are able to ascertain the relative efficacy of BVS compared with DEB and EES in these patients.
The results of the current study suggest that BVS are safe and effective in patients with ISR. In addition, our findings indicate that, in this challenging anatomic scenario, the late angiographic and clinical outcomes of BVS are similar to those obtained with DEB but remain poorer than those achieved with EES.
WHAT IS KNOWN? Current clinical practice guidelines recommend the use of either DEB or DES in patients with ISR. The value of BVS in this scenario remains unsettled.
WHAT IS NEW? BVS are safe and effective in patients with ISR. In patients with ISR, BVS provide late angiographic and clinical outcomes similar to DEB. However, in this setting the long-term angiographic and clinical efficacy of EES are superior to that obtained with BVS.
WHAT IS NEXT? A longer follow-up is required to confirm the safety and efficacy of this novel strategy. Further studies are required to assess the value of other types of BVS.
For supplemental materials, please see the online version of this article.
All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- bare-metal stent(s)
- bioresorbable vascular scaffolds
- confidence interval
- drug-eluting balloons
- drug-eluting stent(s)
- everolimus-eluting stent(s)
- hazard ratio
- in-stent restenosis
- Received May 9, 2017.
- Revision received June 22, 2017.
- Accepted June 22, 2017.
- 2017 American College of Cardiology Foundation
- Windecker S.,
- Kolh P.,
- Alfonso F.,
- et al.
- Jiménez-Quevedo P.,
- Serrador A.,
- Pérez de Prado A.,
- et al.
- Alfonso F.,
- Fernandez C.
- Dangas G.D.,
- Claessen B.E.,
- Caixeta A.,
- Sanidas E.A.,
- Mintz G.S.,
- Mehran R.
- Alfonso F.,
- Byrne R.A.,
- Rivero F.,
- Kastrati A.
- Grasso C.,
- Attizzani G.F.,
- Patané M.,
- Ohno Y.,
- Capodanno D.,
- Tamburino C.
- Alfonso F.,
- Nuccio J.,
- Cuevas C.,
- Cardenas A.,
- Gonzalo N.,
- Jimenez-Quevedo P.
- Deora S.,
- Shah S.,
- Pancholy S.,
- Patel T.
- Rivero F.,
- Bastante T.,
- Cuesta J.,
- Benedicto A.,
- Restrepo J.A.,
- Alfonso F.
- Moscarella E.,
- Varricchio A.,
- Stabile E.,
- et al.
- Jamshidi P.,
- Nyffenegger T.,
- Sabti Z.,
- et al.
- Moscarella E.,
- Ielasi A.,
- Granata F.,
- et al.
- Alfonso F.,
- Pérez-Vizcayno M.J.,
- Cárdenas A.,
- et al.
- Alfonso F.,
- Pérez-Vizcayno M.J.,
- Cárdenas A.,
- et al.
- Cutlip D.E.,
- Windecker S.,
- Mehran R.,
- et al.
- Mehran R.,
- Dangas G.,
- Abizaid A.S.,
- et al.
- Alfonso F.,
- Pérez-Vizcayno M.J.,
- García Del Blanco B.,
- et al.
- Serruys P.W.,
- Chevalier B.,
- Sotomi Y.,
- et al.