title: Comprehensive Assessment of Coronary Plaque Progression With Advanced Intravascular Imaging, Physiological Measures, and Wall Shear Stress: A Pilot Double-Blinded Randomized Controlled Clinical Trial of Nebivolol Versus Atenolol in Nonobstructive Coronary Artery Disease.
abstract: BACKGROUND
  We hypothesized that nebivolol, a β-blocker with nitric oxide-mediated activity, compared with atenolol, a β-blocker without such activity, would decrease oxidative stress and improve the effects of endothelial dysfunction and wall shear stress (WSS), thereby reducing atherosclerosis progression and vulnerability in patients with nonobstructive coronary artery disease.
  
  
  RESULTS
  In this pilot double-blinded randomized controlled trial, 24 patients treated for 1 year with nebivolol 10 mg versus atenolol 100 mg plus standard medical therapy underwent baseline and follow-up coronary angiography with assessments of inflammatory and oxidative stress biomarkers, microvascular function, endothelial function, and virtual histology intravascular ultrasound. WSS was calculated from computational fluid dynamics. Virtual histology intravascular ultrasound segments were assessed for vessel volumetrics and remodeling. There was a trend toward more low-WSS segments in the nebivolol cohort (P=0.06). Low-WSS regions were associated with greater plaque progression (P<0.0001) and constrictive remodeling (P=0.04); conversely, high-WSS segments demonstrated plaque regression and excessive expansive remodeling. Nebivolol patients had decreased lumen and vessel areas along with increased plaque area, resulting in more constrictive remodeling (P=0.002). There were no significant differences in biomarker levels, microvascular function, endothelial function, or number of thin-capped fibroatheromas per vessel. Importantly, after adjusting for β-blocker, low-WSS segments remained significantly associated with lumen loss and plaque progression.
  
  
  CONCLUSIONS
  Nebivolol, compared with atenolol, was associated with greater plaque progression and constrictive remodeling, likely driven by more low-WSS segments in the nebivolol arm. Both β-blockers had similar effects on oxidative stress, microvascular function, and endothelial function.
  
  
  BACKGROUND
  URL: https://clinicaltrials.gov/. Unique identifier: NCT01230892.
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.).
authors.forename: Olivia Y
authors.initials: OY
authors.lastname: Hung
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (D.M., L.H.T., D.P.G.).
authors.forename: David
authors.initials: D
authors.lastname: Molony
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.).
authors.forename: Michel T
authors.initials: MT
authors.lastname: Corban
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.).
authors.forename: Emad
authors.initials: E
authors.lastname: Rasoul-Arzrumly
authors.affiliation: Department of Health Services, University of Washington, Seattle, WA (C.M.).
authors.forename: Charles
authors.initials: C
authors.lastname: Maynard
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.).
authors.forename: Parham
authors.initials: P
authors.lastname: Eshtehardi
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.).
authors.forename: Saurabh
authors.initials: S
authors.lastname: Dhawan
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.) Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (D.M., L.H.T., D.P.G.).
authors.forename: Lucas H
authors.initials: LH
authors.lastname: Timmins
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (M.P.).
authors.forename: Marina
authors.initials: M
authors.lastname: Piccinelli
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.) Division of Cardiology, Department of Internal Medicine, Yonsei UniversityWonju College of Medicine, Wonju, Republic of Korea (S.G.A.).
authors.forename: Sung Gyun
authors.initials: SG
authors.lastname: Ahn
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.).
authors.forename: Bill D
authors.initials: BD
authors.lastname: Gogas
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.).
authors.forename: Michael C
authors.initials: MC
authors.lastname: McDaniel
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.).
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA (D.M., L.H.T., D.P.G.).
authors.forename: Don P
authors.initials: DP
authors.lastname: Giddens
authors.affiliation: Division of Cardiology, Department of Medicine, Andreas Gruentzig Cardiovascular Center, Emory University School of Medicine, Atlanta, GA (O.Y.H., M.T.C., E.R.A., P.E., S.D., L.H.T., S.G.A., B.D.G., M.C.M.D., A.A.Q., H.S.).
authors.forename: Habib
authors.initials: H
authors.lastname: Samady
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D001262:Atenolol / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D003952:Diagnostic Imaging / Q000379:methods; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D005260:Female; D005845:Georgia; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010865:Pilot Projects; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D013314:Stress, Mechanical; D013997:Time Factors; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D000068577:Nebivolol; D001262:Atenolol
keywords: coronary flow; coronary microvascular function; endothelial function; intravascular ultrasound; wall shear stress
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