Patient population and data collection

This was a prospective, multicenter, non-randomized study that compared 3 different types of DES: a) the durable polymer-coated everolimus-eluting stent Xience DES (Abbott, United States); b) the biodegradable polymer-coated everolimus-eluting stent Synergy DES (Boston Scientific, United States), and c) the polymer-free BES Biofreedom DES (Biosensors International Ltd, Singapore). The study was conducted at 4 Spanish teaching hospitals.

A total of 144 patients were consecutively recruited from January 2018 through December 2019. Patients were eligible if they had been admitted due to stable coronary artery disease or acute coronary syndrome without cardiogenic shock. The medical team selected the type of stent that should be implanted. The detailed study flowchart is shown on figure 1. Inclusion criteria were a) de novo lesions; b) ≥ 1 target lesions in the same or different coronary artery; c) no need for stent overlapping, and a 10 mm minimal distance between the stents; d) stent length between 8 mm and 30 mm; e) use of stents with diameters ≥ 2.5 mm.

Figure 1. Flowchart of patient inclusion. 

Exclusion criteria were a) complex lesions including ostial lesions, chronic total coronary occlusions, calcified lesions requiring calcium modification techniques, and bifurcations requiring the kissing balloon technique; b) target lesions in small vessels (< 2.5 mm) and long lesions (> 30 mm) requiring small diameter stents (2.25 mm) or overlapping stents; c) diabetic patients; d) very tortuous arteries that anticipated the impossibility of access with the OCT catheter for follow-up purposes; and e) complications during index procedure. Patients with diabetes mellitus were excluded from the study because of their pro-inflammatory status that facilitates both stent thrombosis and restenosis.¹⁸

Once recruited, patients were consecutively assigned to a 1- or 6-month OCT follow-up group. The baseline characteristics, angiographic and procedural data, follow-up data, and outcome data were prospectively collected by the study coordinators. Clinical data at follow-up were obtained from the clinical records. This study was performed following the principles established by the Declaration of Helsinki, ISO14155, and the clinical practice guidelines. The study protocol was approved by the Institutional Ethics Committee (IEC) and the hospital research committee. Informed consent was obtained from all the patients.

Percutaneous coronary intervention, angiographic analysis, and optical coherence tomography

In the index procedure stents were implanted according to the standard approach. Patients were medically treated following the European guidelines on the management of chronic ischemic heart disease or acute coronary syndrome.¹⁹

Regarding the initial angiographic analysis, 2 orthogonal projections without coronary guidewire were obtained after finishing the index procedure. These same projections were acquired at follow-up. The off-line analysis of the angiographic images (quantitative coronary angiography [QCA]) was performed in an independent core lab (Barcelona Cardiac Imaging Core-Lab [BARCICORElab]), following their standard protocol. They used a dedicated software (CAAS, version 5.9; Pie Medical BV, The Netherlands). Methods used in this core lab have been previously reported²⁰.

The follow-up angiography was performed at 1-or-6-month follow-up. Angiographic and OCT images were obtained from each patient. The Dragonfly frequency domain OCT C7-XR system (St. Jude Medical, United States) was used. This analysis was performed at the same independent core lab with a dedicated software (St. Jude Medical). Further information can be found on the supplementary data. The struts were classified as non-covered if their surface was totally or partially exposed to the lumen, and without any tissue coverage above its high-density scaffold. Stent strut apposition was defined as the perpendicular distance between the luminal edge of the strut and the vascular wall. Incomplete apposition was considered when distance was higher compared to the total strut thickness considering the addition of strut plus polymer. Intimal hyperplasia was measured as the perpendicular distance between the luminal surface of the stent strut and the luminal surface of the neointima.

Endpoints

The study primary endpoint was the percentage of uncovered struts among durable-polymer EES vs biodegradable-polymer EES vs polymer-free BES as seen on the OCT at 1 month.

The study secondary endpoint was to compare the coverage and apposition of these 3 different types of DES on the OCT 1 vs 6 months after implantation. In addition, we evaluated the intimal hyperplasia in the 3 stent groups over time.

Statistical analysis

Continuous variables were expressed as mean and standard deviation except when they did not follow normal distribution, in which case they were expressed as median and 25^th-75^th percentile. Categorical variables were expressed as frequency and percentage. The analysis of the clinical differences was performed using the chi-square test or Fisher's exact test for qualitative variables. Comparison among quantitative variables was performed using the 1-way ANOVA test. Generalized estimating equations, considering the clustering nature of the OCT data, were used to conduct analyses at strut level. All probability values were two-sided, P values < .05 were considered statistically significant. Statistical analysis was performed using the SPSS software package, version 22.0 (SPSS, United States). The sample size estimate is shown on the supplementary data.

Baseline clinical characteristics

A total of 104 patients from 4 different hospitals were included in the study; 44 patients were treated with a polymer-free BES, 35 with a biodegradable-polymer EES, and 25 patients with a durable-polymer EES. Of these, 37 patients underwent follow-up angiography and OCT 1 month after DES implantation, and 67 patients after 6 months. Mean age was 57 years; most patients were man (11% women). The inter-group baseline clinical characteristics are shown on table 1 according to the type of stent implanted. We observed a statistically significant difference in the left ventricular ejection fraction that was slightly lower in patients who received a polymer-free BES (54% vs 60%). The number of patients who needed postdilatation was higher in the durable-polymer EES group (68%) especially compared to the polymer-free BES group (38%).

Procedural and lesion characteristics

Procedural characteristics based on the type of stent implanted are shown on table 1. We found no significant differences in stent diameter or length in the 3 stent groups. The left anterior descending coronary artery was the most treated of all whereas secondary arteries were scarcely included in this study.

Angiographic analysis

The lesion angiographic characteristics are shown on table 2 and table 1 of the supplementary data. There were 2 patients with angiographic images with insufficient quality for analysis, both from the biodegradable-polymer EES group. There were no significant differences in the lesions before or after the PCI. After 1 month, no significant differences were reported regarding lumen loss or percent diameter stenosis. No differences were reported among the 3 stent groups at 6 months.

OCT outcomes

OCT results are shown on table 3, and table 2 in the supplementary data. There were 6 patients with OCT images with insufficient quality for analysis, 2 from the polymer-free BES, 3 from the biodegradable-polymer EES group, and 1 from the durable-polymer EES group. Stent strut coverage and apposition were analyzed, as well as neointimal hyperplasia. Overall, 15 906 struts were examined. Of these, 4380 struts were from durable-polymer EES; 5122 from biodegradable-polymer EES; and 6404 from polymer-free BES; 6184 and 9722 struts were analyzed at 1 and 6 months, respectively.

A high rate of uncovered struts was found among stents 1 month after implantation, with no significant differences (P = .209). We observed ≥ 5% of uncovered struts in > 80% of the patients. There was better coverage in the 3 stent groups at 6 months compared to 1 month (P < .001 polymer-free BES; P = .007 biodegradable-polymer EES; P = .001 durable-polymer EES). No statistically significant differences were reported in strut coverage at 6 months among the different stents (P = .172) (figure 2, figure 3A).

Figure 2. Endpoint comparison at 1 and 6 months. A: percentage of struts covered at 1 and 6 months; B: percentage of struts apposed at 1 and 6 months; C: neointimal hyperplasia at 1 and 6 months. BES, biolimus-eluting stent; EES, everolimus-eluting stent. 

Figure 3. Optical coherence tomography. A: optical coherence tomography showing covered and uncovered stent struts at 1 and 6 months; B: optical coherence tomography showing malapposed stent struts at 1 and 6 months. BES, biolimus-eluting stent; EES, everolimus-eluting stent; MO, months. 

Regarding strut apposition to the artery walls, no significant differences were reported among the 3 stents after 1 month (P = .497). We observed ≥ 5% of malapposed struts in 29% to 30% of the patients with no differences among stents. No significant differences were reported among the stents after 6 months either. The rate of apposition was higher at 6 months compared to 1 month in all stent groups (P < .001 polymer-free BES; P = .001 biodegradable-polymer EES; P = .029 durable-polymer EES) (figure 2, figure 3B).

When we analyzed neointimal hyperplasia, no significant differences were found at 1 month among the 3 stent groups (P = .083). At 6 months, we found higher hyperplasia in the polymer-free BES compared to the durable-polymer EES (P < .001). We found more hyperplasia at 6 months compared to 1 month in all groups (P < .001 polymer-free BES; P < .001 biodegradable-polymer EES; P = .005 durable-polymer EES; figure 2).

Study limitations

This was an OCT-based study; unfortunately, it was not powered to assess clinical outcomes. Our study was non-randomized. However, we minimized the confounding factors through selected inclusion/exclusion criteria for patients and lesions (non-diabetic patients with non-complex coronary lesions). We analyzed the differences among the groups and no significant differences were found, except in the left ventricular ejection fraction, which was significantly lower in the group of polymer-free stents. It has not been described in the medical literature whether a lower left ventricular ejection fraction has any correlation with stent thrombosis. This study included selected non-diabetic patients with simple coronary artery lesions. Therefore, the conclusions cannot be extrapolated to other groups with different characteristics.

The distribution of patients who underwent the follow-up angiography in the polymer-free DES group at 1 or 6 months was uneven. More patients rejected the follow-up angiography at 1 month in the polymer-free DES group, which may account for this difference. Finally, the complexity of the analysis of 3 different groups in 2 different moments of time caused a disgregation of cases. This led to a small N in each group, with the potential biases associated.