title: Effect of Angiotensin II Type I Receptor Blockade with Valsartan on Carotid Artery Atherosclerosis: A Double Blind Randomized Clinical Trial Comparing Valsartan and Placebo (EFFERVESCENT).
abstract: BACKGROUND
  Progression of atherosclerosis is associated with a greater risk for adverse outcomes. Angiotensin II plays a key role in the pathogenesis and progression of atherosclerosis. We aimed to investigate the effects of angiotensin II type-1 receptor blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis.
  
  
  METHODS
  Subjects (n = 120) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan or placebo for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area and wall thickness were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium-dependent and -independent vascular function.
  
  
  RESULTS
  Over 2 years, the carotid bulb vessel wall area decreased with Valsartan (-6.7, 95% CI [-11.6, -1.9] mm(2)) but not with placebo (3.4, 95% CI [-2.8, 9.6] mm(2)), P = .01 between groups. Similarly, mean wall thickness decreased with Valsartan (-0.18, 95% CI [-0.30, -0.06] mm), but not with placebo (0.08, 95% CI [-0.07, 0.23] mm), P = .009 between groups. Furthermore, plaque thickness decreased with Valsartan (-0.35, 95% CI [-0.63, -0.08] mm) but was unchanged with placebo (+0.28, 95% CI [-0.11, 0.69] mm), P = .01 between groups. These findings were unaffected by statin therapy or changes in blood pressure. Notably, there were significant improvements in the aminothiol cysteineglutathione disulfide, and trends to improvements in fibrinogen levels and endothelium-independent vascular function.
  
  
  CONCLUSIONS
  In subjects with carotid wall thickening, angiotensin II type-1 receptor blockade was associated with regression in carotid atherosclerosis. Whether these effects translate into improved outcomes in subjects with subclinical atherosclerosis warrants investigation.
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Department of Medicine, Emory University School of Medicine, Atlanta, GA. Electronic address: rramadan@bidmc.harvard.edu.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Ramadan
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Saurabh S
authors.initials: SS
authors.lastname: Dhawan
authors.affiliation: Department of Biostatistics & Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA.
authors.forename: José Nilo G
authors.initials: JN
authors.lastname: Binongo
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Ayman
authors.initials: A
authors.lastname: Alkhoder
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine and Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA.
authors.forename: John N
authors.initials: JN
authors.lastname: Oshinski
authors.affiliation: Emory Clinical Cardiovascular Research Institute, Department of Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D050197:Atherosclerosis / Q000175:diagnosis / Q000188:drug therapy*; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000188:drug therapy*; D059168:Carotid Intima-Media Thickness; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D000068756:Valsartan / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000068756:Valsartan