Drug-eluting stents (DES) have reduced the rate of in-stent restenosis dramatically in comparison with bare-metal stents (BMS). Still, there are "safety concerns" in form of late and very late stent thrombosis.
Multifactorial predictors may be associated with later thrombotic events, but delayed arterial healing has been documented the most powerful predisposing factor in previous histo-pathological studies. Culprit lesions in patients having DES-implantation due to myocardial infarction are associated with substantial delay in arterial healing in comparison with patients having DES-implantation due to stable coronary artery disease.
Numerous procedural factors are also of significant importance with regard to sufficient coronary vessel wall healing. Particularly, acute incomplete stent apposition (ISA) is a strong procedural risk factor for delayed coverage.
Optical coherence tomography (OCT) is a high-resolution intravascular imaging modality, which enables detailed in-vivo assessment of the immediate stenting result and the vascular healing pattern, including strut coverage, at follow-up.
Some procedural factors can be modified using OCT-guidance, potentially leading to a decrease in the proportion of uncovered struts at follow-up.
The hypothesis of the study is that OCT-guided PCI can reduce the incidence of acute and late ISA, and thereby provide improved strut coverage following Nobori-stent implantation.
The objective of this study is to assess whether OCT-guided optimization following Nobori stent implantation in patients with Non ST segment Elevation Myocardial Infarction (NSTEMI) improves the coronary vascular response in comparison with routine angiographic guidance alone.
The present study is designed as a prospective, randomized trial conducted at a single center (Odense University Hospital). One-hundred patients were enrolled (Between August 2011 and May 2013). Prior to the PCI procedure, patients were loaded with a 300 mg dose of aspirin, and a loading dose of 180 mg ticagrelor. An unfractionated heparin dose (70 IU/kg) was administered just before the PCI-procedure. In all cases the third-generation biolimus-eluting stent (Nobori, Terumo, Tokyo, Japan) was implanted.
Stents were implanted according to standard techniques. Recommended post-procedure dual antiplatelet regimens were 75 mg aspirin daily lifelong and 90 mg ticagrelor twice daily for 1 year.
Post-implantation, after acquisition of an angiographic optimal result, patients were randomly assigned 1:1 to either: 1) OCT-guided PCI, or 2) angio-guided PCI. Random assignments were distributed in sealed envelopes.
Both treatment arms had post-procedure OCT and IVUS performed after administration of 200 micrograms of intracoronary nitroglycerin. It was not possible to blind the operator, investigator or patient for the allocated implantation technique, but the operator was blinded to the post-procedure OCT- and IVUS images in the angio-guided group, as the operator screen-side was turned off, and the entire pullbacks remained uncommented on. In the OCT-guided group, images were interpreted online by a dedicated OCT-analyst and the PCI-operator.
If the post-procedure OCT revealed: 1) under expansion of the stent with a minimal stent area (MSA) \<90% of the distal/proximal reference vessel lumen area, and/or 2) significant acute ISA (defined as more or equal to 3 struts per cross sectional area detached more than 140 microns (thickness of strut + drug/polymer coating)) from the underlying vessel wall, and/or 3) edge dissection(s) causing significant reduction in minimal lumen area(s) (MLA\<4 mm2) and/or 4) significant residual stenosis (MLA\<4 mm2) at the proximal and/or distal reference segment(s) additional intervention was encouraged. The degree of optimization based upon OCT findings was left to the judgement of the PCI-operator.
Patients were scheduled for both a 6-months clinical and invasive (including angiogram and OCT) and a 12-months clinical and invasive (including angiogram, OCT and IVUS) follow-up.
Prior to follow-up imaging, 5,000 IU of unfractionated heparin and 200 micrograms of intracoronary nitroglycerin was administered.
OCT was performed both post-procedure, at 6-months and at 12-months using a frequency-domain OCT system (C7-XR or Ilumien system). A 2.7 Fr C7 Dragonfly imaging catheter flushed with 20 ml undiluted contrast was used.
Motorized pullback was performed at a pullback rate of 20 mm/s throughout the stent.
Quantitative OCT analysis is performed using the LightLab OCT proprietary software (Offline Review Workstation). Analysis is performed by one dedicated OCT-analyst, who is blinded to the implantation technique, when assessing 6-months images for strut coverage.
An inter-observer reliability analysis of apposition and coverage will be provided.
Lesions are analyzed at the cross sectional level with an interval of 1 mm (every 5 frames).
Struts devoid of coverage at any part are deemed "uncovered". The neointimal thickness is measured for all covered struts (the thickness is measured as the distance between the endoluminal side of the strut from the midpoint of its long axis and the intersection of the lumen contour with a straight line between the endoluminal side of the strut and the gravitional center of the vessel). Apposition is assessed by measuring the distance between the center of the endoluminal strut side and the gravitional center of the vessel (malapposed strut = detached more than 140 microns from the underlying vessel wall).
Malapposition distances and areas are also traced. The percentage of malapposed and/or uncovered struts are calculated as the number of malapposed and/or uncovered struts/total number of struts in all cross sections of the lesion, multiplied by 100.
The IVUS system (Boston Scientific) utilized a 40 MHz, 2.6 Fr IVUS catheter (Atlantis SR Pro). Image acquisition using automated transducer pullback at 0.5 mm/s was performed from at least 10 mm distal to 10 mm proximal of the stented segment.
Offline analysis is performed with a computerized planimetry program (EchoPlaque). For each 1 mm of axial length, lumen and external elastic membrane (EEM) areas are traced. Stent and reference site parameters (areas and volumes) are calculated. Remodeling (based on baseline and 12-months analysis) is assessed.
SPSS version 22.0 (SPSS Inc., Chicago Illinois) is used for the statistical analysis. All tests are two-tailed, and a p-value \<0.05 is considered statistically significant. Categorical data will be presented as numbers and frequencies, and compared with chi-square or Fisher´s exact statistics. Continuous data will be presented as mean +- SD and compared with the Student´s t-test. If the distributions are skewed, a non-parametric test will be performed, and the median with an interquartile range will be provided.
The primary and secondary endpoints will be assessed by the Kruskal-Wallis test, and an ordered logistic regression analysis adjusted for confounders will be provided.
Powercalculation: A powercalculation with an expected frequency of 0.66 and 0.90 covered struts after 6 months in the angio-guided and OCT-guided group, respectively, shows that 43 patients are to be included in each arm to reach statistical significance. With 43 patients in each treatment arm and a two-sided statistical significance level of 0.05, the study will have a power of 0.8 to show a proportion of 0.66 and 0.90 covered struts at 6-months follow-up in the angio- and OCT-guided group, respectively. With an expected dropout of 14% due to invasive non-compliance and with subject to suboptimal imaging quality, 100 patients are to be enrolled.
