title: Effect of Targeting Inflammation With Salsalate: The TINSAL-CVD Randomized Clinical Trial on Progression of Coronary Plaque in Overweight and Obese Patients Using Statins.
abstract: Inflammation may contribute to pathological associations among obesity, diabetes mellitus, and cardiovascular disease.
  
  
  
  To determine whether targeting inflammation using salsalate compared with placebo reduces progression of noncalcified coronary artery plaque.
  
  
  
  In the Targeting Inflammation Using Salsalate in Cardiovascular Disease (TINSAL-CVD) trial participants were randomly assigned between September 23, 2008, and July 5, 2012, to 30 months of salsalate or placebo in addition to standard, guideline-based therapies. Randomization was computerized and centrally allocated, with patients, health care professionals, and researchers masked to treatment assignment. Participants were overweight and obese statin-using patients with established, stable coronary heart disease.
  
  
  
  Salsalate (3.5 g/d) or placebo orally over 30 months.
  
  
  
  The primary outcome was progression of noncalcified coronary artery plaque assessed by multidetector computed tomographic angiography. Secondary outcomes were other measures of safety and efficacy.
  
  
  
  Two hundred fifty-seven participants were randomized to salsalate (n = 129) or placebo (n = 128). Their mean (SD) age was 60.8 (7.0) years, and 94.0% (236 of 251) were male. One hundred ninety participants (89 in the salsalate group and 101 in the placebo group) completed the study. Compared with baseline, there was no increase in noncalcified plaque volume in the placebo-treated patients and no difference in change between the salsalate and placebo groups (mean difference, -1 mm3; 95% CI, -11 to 9 mm3; P = .87). Salsalate treatment decreased total white blood cell, lymphocyte, monocyte, and neutrophil counts and increased adiponectin levels without change in C-reactive protein levels. Fasting glucose, triglycerides, uric acid, and bilirubin levels were decreased in the salsalate group compared with the placebo group, while hemoglobin levels were increased. Urinary albumin levels increased, with tinnitus and atrial arrhythmias more common, in the salsalate group compared with the placebo group.
  
  
  
  Salsalate when added to current therapies that include a statin does not reduce progression of noncalcified coronary plaque volume assessed by multidetector computed tomographic angiography in statin-using patients with established, stable coronary heart disease. The absence of progression of noncalcified plaque volume in the placebo group may limit interpretation of the trial results.
  
  
  
  clinicaltrials.gov Identifier: NCT00624923.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts2Harvard Medical School, Boston, Massachusetts.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hauser
authors.affiliation: Harvard Medical School, Boston, Massachusetts3Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts4Clinical Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Ninad
authors.initials: N
authors.lastname: Salastekar
authors.affiliation: Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
authors.affiliation: Harvard Medical School, Boston, Massachusetts4Clinical Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Desai
authors.affiliation: The Heart Center of MetroWest, Framingham, Massachusetts.
authors.forename: Harvey L
authors.initials: HL
authors.lastname: Goldfine
authors.affiliation: Clinical Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Fowler
authors.affiliation: Harvard Medical School, Boston, Massachusetts7Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Griffin M
authors.initials: GM
authors.lastname: Weber
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts2Harvard Medical School, Boston, Massachusetts.
authors.forename: Francine
authors.initials: F
authors.lastname: Welty
authors.affiliation: Harvard Medical School, Boston, Massachusetts3Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Melvin
authors.initials: M
authors.lastname: Clouse
authors.affiliation: Harvard Medical School, Boston, Massachusetts4Clinical Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Shoelson
authors.affiliation: Harvard Medical School, Boston, Massachusetts4Clinical Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts8Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Allison B
authors.initials: AB
authors.lastname: Goldfine
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009765:Obesity; D050177:Overweight; D058226:Plaque, Atherosclerotic / Q000188:drug therapy*; D012459:Salicylates / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012459:Salicylates; C014182:salicylsalicylic acid