Effect of Targeting Inflammation With Salsalate: The TINSAL-CVD Randomized Clinical Trial on Progression of Coronary Plaque in Overweight and Obese Patients Using Statins

IMPORTANCE: Inflammation may contribute to pathological associations among obesity, diabetes mellitus, and cardiovascular disease. OBJECTIVE: To determine whether targeting inflammation using salsalate compared with placebo reduces progression of noncalcified coronary artery plaque. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: Salsalate (3.5 g/d) or placebo orally over 30 months. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00624923