Bioresorbable scaffold implantation in STEMI patients: 5 years imaging subanalysis of PRAGUE-19 study

The PRAGUE-19 study is a prospective two-centre open-label registry of consecutive STEMI patients. One hundred and thirty-four consecutive STEMI patients fulfilled the inclusion criteria and were treated with Absorb™ BRS version 1.1 during the enrolment period between December 2012 and December 2015. The design, short-term results of the pilot study phase and subsequently interim analysis of three years clinical and imaging results have been published previously [9, 10]. This article represents the imaging analysis of the first 25 patients available for the 5 year invasive assessment as planned in the study protocol and approved by the ethical committee. Article also presents interim analysis of five-year clinical follow-up of patients enrolled from December 2012 until March 2014, this study cohort is available for five-year outcome assessment in March 2019. During this period, 83 patients fulfilled the inclusion criteria for Absorb™ BRS implantation; this device was successfully implanted in 81 (97%) patients. In two patients, Absorb™ BRS could not be delivered to the culprit lesion and a metallic stent was used instead. The study protocol mandated dual antiplatelet therapy for 12 months after Absorb™ BRS implantation and all our patients adhered to this protocol. The study was approved by the local ethics committee at each centre as well as by the national multicentric ethics committee, and written informed consent was obtained from all study patients. The originally planned coronary angiography with optical coherence tomography (OCT) at three-year follow-up was postponed to five years after analysis of three-year results demonstrating incomplete resorption of the Absorb™ BRS device [10]; study protocol was amended and invasive assessment was approved for the first 25 patients by all ethics committees again. Complete clinical follow-up of all patients included in the study as well as patients in the control group is planned and will be finished in December 2020. This study was conducted according to the Declaration of Helsinki.

The 5-year clinical follow-up was evaluated in 79 of 81 patients with implanted Absorb™ BRS (two patients were lost to follow-up). The study flow chart is presented in Fig. 1. The prespecified primary endpoint of the study was a combination of death, MI and target vessel revascularization (TVR). BRS thrombosis was defined according to the Academic Research Consortium definitions [11]. All patients had quantitative coronary angiography (QCA) off-line analysis of angiogram after completion of primary percutaneous coronary intervention (PCI). Optical coherence tomography in the acute phase at the end of primary PCI was recommended but not mandatory (the most common reason not to perform OCT was patient hemodynamic instability or clinically significant arrhythmia). Invasive coronary imaging at five years was performed only in patients who agreed with the research procedure and did not undergo repeat coronary angiography at three-year follow-up. All invasive studies at five-year follow-up included OCT. Intracoronary nitrate has been injected into all studied arteries prior to imaging. All procedures were performed via radial artery approach without any complications, most patients were discharged on the same day.

For each angiogram, QCA was performed using Philips Xcelera software (Philips Medical Systems, Eindhoven, The Netherlands). Identical or at least similar projections were used for comparison of baseline study at the end of primary PCI with the five-year follow-up study. The treated segment was defined as 5 mm proximal and distal to the visible proximal and distal Absorb™ BRS markers. Image calibration was performed with a contrast-filled 6 French guiding catheters. The following QCA parameters were measured: proximal and distal reference vessel diameter (RVD), minimal lumen diameter (MLD), mean lumen diameter, scaffold length between the 2 markers, Mean RVD was calculated as average of proximal and distal RVD. Diameter stenosis was calculated from the MLD and mean RVD and expressed as a percentage. Late lumen loss was defined as MLD at five-year follow-up angiography minus MLD at baseline study at the end of primary PCI. The presence of coronary artery aneurysm was defined by focal vessel dilatation with diameter at least 50% larger than the adjacent reference segment [12].

Technique of OCT acquisition at the end of primary PCI has been described previously [9]. OCT at five-year follow-up was performed using the frequency domain C7 system with a Dragonfly Duo catheter (St. Jude Medical, St. Paul, MN, USA), a pullback speed of 20 mm/sec, and an image acquisition of 100 frames/sec. OCT off-line analysis was performed using the proprietary software (ILUMIEN OPTIS system, Light Lab Imaging, Westford, MA, USA) which has a validated reproducibility [13]. All OCT measurements were based on previously published standards [14]. However, some adjustments were required due to Absorb™ BRS complete resorption at five years post implantation. At first, proximal and distal scaffold markers were identified on the OCT pullback. The design of Absorb™ BRS is such, that the scaffold edges extend beyond the markers by 0.3 mm at the distal end and by 0.9–1.3 mm at the proximal end [15]. We have therefore measured proximal and distal reference vessel area and mean diameter as a mean value of frames at the distance between 2 and 5 mm from the scaffold markers (Fig. 2). Scaffold area/diameter (baseline OCT) and lumen area/diameter (five-year OCT) were measured at vessel cross-sections at 1 mm intervals. Mean scaffold/lumen area and diameter were calculated as mean of all-cross-sections between the scaffold markers. Minimal lumen area/diameter were measured at the site of the smallest lumen between the scaffold markers. It is not possible to measure neointimal hyperplasia area in the absence of stent/scaffold struts. The number of visible struts was noted in each 1 mm cut. Coronary artery dissection, the presence of thrombus and coronary artery aneurysm were all recorded in every patient.

Standard descriptive statistics were applied in the analysis: absolute and relative frequencies for categorical variables; continuous variables were described using the mean supplemented with standard deviation. The statistical significance of changes in continuous variables (QCA and OCT) between baseline and 5-year follow-up was tested using a paired t-test. P-values < 0.05 were considered statistically significant. Statistical analysis was computed using SPSS 23.0.0.0 (IBM Corp., Armonk, NY, USA).

Baseline characteristics of 79 patients with implanted Absorb™ BRS are shown in Table 1. During the five-year follow-up period the primary endpoint (combination of death, MI and TVR) occurred in 10 patients (12.6%) with overall mortality of 6.3%. There were 3 cardiovascular deaths (all sudden deaths) at 14 days, 9 months and 51 months after Absorb™ BRS implantation. Two patients died due to cancer (brain and prostatic) at 40 and 50 months after BRS implantation. Two patients suffered of reinfarction (one subacute BRS thrombosis after ticagrelor discontinuation, one culprit lesion in different coronary artery tree) and three patients of TVR (one BRS restenosis and 2 native lesions not related to BRS segment) during the first 12 months. Except one sudden cardiac death and two non-cardiac deaths, there were no other clinical events after 12 months when dual antiplatelet therapy was stopped. All clinical events are summarized in Table 2.

The results of QCA analysis performed at baseline and after five years are presented in Table 3. All patients had coronary angiograms available for analysis. There is no difference in scaffold length and reference vessel diameters. Late lumen loss was only 0.11 ± 0.35 mm after five years. There was no stenosis over 50% of diameter. Diameter stenosis was 15.6 ± 15.9% at baseline and 18.9 ± 8.3% (p = 0.05) after five years. Figure 3 shows coronary angiography of all patients with identical or similar fluoroscopic view at baseline and at five-year follow up (N = 24). One patient (No 16) did not have similar fluoroscopy views available and the coronary angiography in different views is available in online Supplement 1. Three patients developed new coronary artery aneurysm (patients 6, 9 and 10 in Fig. 3). All were small with maximum diameter between 50–100% larger than the adjacent reference vessel diameter.

Baseline OCT was available in 15 patients. All 25 patients had OCT performed at the time of five-year follow-up, but three patients were excluded from analysis due to sub-optimal image quality precluding clear identification of scaffold markers. Table 4 presents paired comparison of 14 patients who had both baseline and five-year OCT available for analysis. There is no difference in reference vessel dimensions. Scaffold mean area at baseline is similar to lumen mean area after five years; 8.46 ± 1.55 mm² versus 7.9 ± 2.12 mm² (P = 0.13). Scaffold and lumen mean diameters at baseline and after five years are nearly identical. There were no scaffold struts and no thrombi present after five years. Analysis of segments with three new coronary artery aneurysms showed normal arterial three-layer structure and did not demonstrate any thrombi or dissections (Fig. 4).

Results of Prague-19 study 5-year follow-up together with recently published ISAR-Absorb MI trial one-year safety data could lead to clinical testing of new generation BRS in patients with STEMI.