2.1

Study Design and Population

This was a prospective, randomized, controlled trial comparing 6, 9 and 12-month OCT findings after EES (Xience™, Abbott vascular, Santa Clara, California, USA) implantation. All the patients who met all the inclusion/exclusion criteria were randomized 1:1:1 to receive an OCT imaging study at 6-month (group A), 9-month (group B) or 12-month (group C). Inclusion criteria were presence of one or two de novo lesions in a native coronary artery including lesions with a diameter stenosis of at least 75% (visual estimate) or a functional study documenting the hemodynamic relevance of the target lesion with reference vessel diameters (RVD) ranging from 2.5 to 3.5 mm. Exclusion criteria were left main disease, ST-elevation myocardial infarction, ostial, severely calcified or thrombotic lesions, severe angulation or tortuosity of the vessel, allergy or contraindication to prolonged treatment with aspirin or clopidogrel, anticoagulation therapy, comorbidity with short expectancy of life, chronic renal disease (serum creatinine more than 2 mg/dl) and impossibility to perform follow-up. The study was approved by the local Ethical committee and all patients provided written informed consent.

2.2

Study Procedures

Device implantation was performed according to standard technique. Pre-dilatation, post-dilatation, and bailout stenting were left to operator’s discretion. All the patients received loading dose of aspirin (300 mg) and clopidogrel (600 mg) before the procedure and 100 IU/kg of intra-venous unfractionated heparin during the procedure. After stent implantation, dual antiplatelet therapy (aspirin 100 mg and 75 mg of clopidogrel daily) was prescribed to all the patients for 12 months.

2.3

Angiographic Analysis

Quantitative coronary angiographic (QCA) analysis was performed offline by an expert analyst in the independent core laboratory of the Hospital Clinic, blinded to follow-up time, using automated edge-detection algorithms (CMS version 6.0, Medis Medical Imaging Systems, Leiden, The Netherlands). Lesion complexity was analyzed according to the AHA/ACC lesion classification . In each lesion, the coronary segment including the stent and 5-mm proximal and distal to the stent edges were analyzed at baseline and at follow-up. Reference vessel diameter (RVD), the minimal lumen diameter (MLD) and the percent diameter stenosis (%DS) were analyzed. Late loss was estimated as the difference between the MLD at post-implantation and at follow-up using matched angiographic views. Binary restenosis was defined as stenosis > 50% of the luminal diameter in the target lesion. To evaluate intraobserver variability, the analyst repeated the analysis 3 months later.

2.4

OCT Imaging and Analysis

OCT imaging was performed at follow-up and performed after intracoronary nitroglycerin injection, using the C7XR Fourier-Domain System (LightLab Imaging, Westford, Massachusetts) . OCT data were analyzed at the independent core laboratory of the Hospital Clinic by an expert analyst, blinded to time of follow-up, using proprietary offline software. (LightLab Imaging, Westford, Massachusetts).

Quantitative analysis was performed at 1 mm intervals within the stent segment and 5 mm proximal and distal to the stent edges. The OCT software drew the lumen area automatically. Stent area was drawn at the adluminal site of the metallic struts. The neointima area was calculated as the difference between the stent and luminal areas. The coverage thickness of > 0 μm on the top of each strut (tissue can be identified above the struts) has been used to classify struts as covered or uncovered . The neointima thickness was automatically calculated from the center of the adluminal side of the strut to the lumen contour with the thickness ruler tool. According to the strut thickness of the used metallic stent (81 μm) and the resolution of the OCT images, a negative value larger than 100 μm was considered as non-covered and non-apposed. Values from 0 to − 100 μm were considered as non-covered and apposed. In case of non-apposed struts with clear neointima tissue above the adluminal side of the strut an extra mark was drawn in order to consider this strut as covered and non-apposed . Stent strut at the bifurcated lesion were excluded in this calculation for NIT. The number of uncovered struts per cross-section was counted and the ratio of uncovered to total struts per section (RUTSS) > 30% was calculated, as previously described .

2.5

Clinical Outcomes

Clinical data were obtained at 12-month follow-up for all the patients. All cause death included non-cardiac and cardiac death. The cardiac death was defined as any death due to immediate cardiac cause (myocardial infarction, low-output failure and fatal arrhythmia), death related to the procedure or death of unknown cause. Target lesion revascularization (TLR) was defined as either PCI or coronary artery bypass grafting owing to restenosis or other complications of the target lesion. Stent thrombosis was defined according to Academic Research Consortium criteria .

2.6

Statistical analysis

Categorical variables were presented as numbers and percentages and compared between groups by Fisher exact tests. Continuous data were shown as mean value ± standard deviation or median and interquartile range, as appropriate, and they were compared using the Kruskal-Wallis Test. No adjustment for clustering or correlated observations in the same subjects was performed due to the small number of patients enrolled . Intraobserver reproducibility of quantitative QCA and OCT measurements were calculated by intraclass correlation coefficient for repeated measurement. For the strut-level and cross-section level analyses, strut apposition and coverage were assessed taking random effects at patient-level into account.

No power calculation was performed. Due the exploratory nature of our analysis, a minimum of 36 patients was decided to include, based on the number of patients enrolled in previous studies . A two-sided p-value < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS (version 19.0, SPSS, Chicago, IL).