Optical Coherence Tomography Guided Percutaneous Coronary Intervention With Stent Implantation
Condition: Coronary Artery Disease; Myocardial Infarction
MeSH terms: Coronary Artery Disease; Myocardial Infarction; Infarction
Study type: Interventional

Summary: 
      Coronary artery disease is one of the most prevalent diseases in the western countries.

      A waxy substance called plaque can build up inside the coronary arteries. Over time, plaque
      can harden or rupture, and cause narrowing (stenosis) of the arteries and reduce the flow of
      oxygen-rich blood to the heart.

      The standard treatment of symptomatic coronary stenosis is percutaneous coronary intervention
      (PCI) with balloon dilation followed by stent implantation.

      A stent is a small metallic grid that stabilizes the coronary vessel wall after the balloon
      dilation.

      Currently, drug-eluting stents (DES) are the most widely used stent types. DESs consist of a
      metallic backbone and an antiprolifetive drug-coating bound by a polymer (glue). These
      devices have reduced the incidence of excessive formation of new tissue (in-stent restenosis)
      dramatically in comparison with previously used bare-metal stents.

      However, there are "safety concerns" with DES, since later thrombotic events have been
      reported.

      On one hand excessive tissue formation inside the stent can cause in-stent restenosis, and on
      the other hand insufficient coverage of the stent can cause persistently exposed metalllic
      material that can induce platelet aggregation and thrombus-formation.

      The etiology to stent thrombosis is multifactorial. Possible predisposing factors are, among
      others: 1) hypersensitivity towards the polymer-coating, which may induce delayed healing
      inside and around the stent, and 2) insufficient contact between the stent and the underlying
      coronary vessel wall (incomplete stent apposition), which may cause flow-disturbance and
      delayed healing.

      Delayed healing causes persistently exposed metallic material that can induce platelet
      aggregation and thrombus-formation.

      The Nobori stent is a new-generation DES, coated with a thin layer of drug and a
      bioabsorbable polymer. The drug is localized on the outer side of the stent, and decreases
      the release of drug to the blood circulation. The bioabsorbable polymer is degraded after 6-9
      months after implantation, and decreases the risk of hypersensitivity-reactions in the vessel
      wall.

      The improved pharmacokinetic profile of the stent is thought to improve the healing pattern.

      At routine coronary angiography, a small plastic tube is inserted in the femoral artery under
      local anesthesia. Thin, flexible catheters are then advanced through the artery system
      (femoral artery and aorta) to the coronary arteries. Contrast is injected in to the blood
      stream by the catheters, and the arteries are depicted by a special X-ray technique during
      dye-release. By angiography, the outer sides of the coronary arteries are visualized, and
      balloon dilations and stent implantations are guided by this standard technique.

      Newer studies have documented that stent placement and expansion is superiorly visualized if
      supplementary intravascular imaging is performed during stent implantation.

      Small imaging catheters are wired through the vessel after stent implantation, and film the
      stent retrogradely through the vessel.

      Intravascular ultrasound (IVUS) visualizes the complete vessel wall by use of sound waves,
      and stent expansion is evaluated in detail.

      Optical coherence tomography (OCT) is a newer light-based, high-resolution technology. The
      technique can depict every thread (strut) from the stent, enabling visualization of both
      contact between struts and underlying vessel wall immediately after the procedure, and strut
      coverage at follow-up.

      The purpose of this study is to determine whether OCT-guided PCI can improve healing and
      coverage of the stent in comparison with routine angiographic guidance alone in patients
      indicating PCI due to myocardial infarction.

      If OCT-guidance improves coverage of the stent, this might lower the later thrombotic risk.

      Patients hospitalized due to myocardial infarction are randomized either to OCT-guided or
      angio-guided stent implantation in the present study. In both groups the Nobori stent is
      implanted according to standard techniques. In the angio-guided group, implantations are
      guided by angiography alone. OCT- and IVUS analysis are performed after an angiographic
      optimal result for documentary reasons. The operator is blinded towards the image findings,
      and analysis is performed offline later.

      In the OCT-guided group, both OCT and IVUS analysis is interpreted immediately after the
      acquisition. If stent apposition and/or expansion is deemed suboptimal, additional balloon
      dilation and/or stenting is performed. In case of OCT-driven stent optimization, a
      documentary OCT and IVUS is performed to document the final result.

      Patients are readmitted 6 months later for a control angiogram inclusive OCT to assess stent
      coverage.

      Furthermore, patients are readmitted 12 months after the index procedure for a control
      angiogram including OCT and IVUS to assess dynamic vessel wall responses.
    

Detailed description: 
      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.
    

Intervention name(s): Percutaneous coronary intervention with Nobori biolimus-eluting stent implantation
Intervention type(s): Device
Intervention description(s): The third-generation biodegradable polymer Nobori biolimus-eluting stent is implanted in all patients
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: PCI optimization; Coronary Remodeling; Drug-Eluting Stent; Optical Coherence Tomography; Intravascular Ultrasound; Strut Coverage; Strut Apposition; Vascular Healing Pattern