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

• Type of Material: Article
• Authors: Olivia Y. Hung, Emory University; David Molony, Georgia Institute of Technology; Michael T. Corban, Emory University; Emad Rasoul-Arzrumly, Emory University; Charles Maynard, University of Washington; Parham Eshtehardi, Emory University; Saurabh Dhawan, Emory University; Lucas Timmins, Emory University; Marina Piccinelli, Emory University; Sung Gyun Ahn, Emory University; Bill D. Gogas, Emory University; Michael McDaniel, Emory University; Arshed Quyyumi, Emory University; Don Giddens, Emory University; Habib Samady, Emory University
• Language: English
• Date: 2016-01-01
• Publisher: American Heart Association: JAHA
• Publication Version: Final Published Version
• Copyright Statement: © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1161/JAHA.115.002764
• Title of Journal or Parent Work: Journal of the American Heart Association
• ISSN: 2047-9980
• Volume: 5
• Issue: 1
• Grant/Funding Information: Forest Laboratories financed this study.; The NIH Ruth L. Kirschstein National Research Service Awards training grant (5T32HL007745) supported Hung and Eshtehardi.; The American Heart Association Postdoctoral Fellowships supported Molony and Timmins.
• Keywords: LOWERING THERAPY; intravascular ultrasound; coronary flow; Cardiac & Cardiovascular Systems; wall shear stress; REGRESSION; STATIN THERAPY; ENDOTHELIAL DYSFUNCTION; ATHEROSCLEROTIC PLAQUE; IN-VIVO; Cardiovascular System & Cardiology; PROGENITOR CELLS; Life Sciences & Biomedicine; endothelial function; coronary microvascular function; BLOOD-PRESSURE
• Research Categories: Health Sciences, Pharmacology; Health Sciences, General

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. METHODS AND 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. CONCLUSION: 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.