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Atherosclerosis. 2015 Jun;240(2):490-6. doi: 10.1016/j.atherosclerosis.2015.03.039. Epub 2015 Mar 28.

The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: a multicenter FDG-PET trial.

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Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Exploratory Clinical & Translational Research, Bristol-Myers Squibb, Princeton, NJ, USA.
Division of Cardiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Division of Atherosclerosis and Vascular Medicine, Baylor College of Medicine and Houston Methdodist DeBakey Heart and Vascular Center, Houston, TX, USA.
Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Peter Munk Cardiac Centre and the Heart and Stroke Richard Lewar Centre of Excellence, The University of Toronto, ON, Canada.
Cardiac MR PET CT Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:



This study evaluated the effect of p38 mitogen-activated protein kinase (p38MAPK) inhibitor, BMS-582949, on atherosclerotic plaque inflammation, using (18)FDG-PET imaging. p38MAPK is an important element of inflammatory pathways in atherothrombosis and its inhibition may lead to reduced inflammation within atherosclerotic plaques.


Subjects with documented atherosclerosis (n = 72) on stable low-dose statin therapy and having at least one lesion with active atherosclerotic plaque inflammation in either aorta or carotid arteries were randomized to BMS-582949 (100 mg once daily), placebo, or atorvastatin (80 mg once daily), for 12 weeks. Arterial inflammation was assessed using (18)FDG-PET/CT imaging of the carotid arteries and aorta. Uptake of arterial (18)FDG was assessed as target-to-background ratio (TBR): 1) as a mean of all slices of the index vessel, and 2) within active slices of all vessels (AS: which includes only slices with significant inflammation (TBR ≥ 1.6) at the baseline).


Treatment with BMS-582949 did not reduce arterial inflammation relative to placebo, (ΔTBR index: 0.10 [95% CI: -0.11, 0.30], p = 0.34; ΔTBR AS: -0.01 [-0.31, 0.28], p = 0.93) or hs-CRP (median %ΔCRP [IQR]: 33.83% [153.91] vs. 16.71% [133.45], p = 0.61). In contrast, relative to placebo, statin intensification was associated with significant reduction of hs-CRP (%ΔCRP [IQR]: -17.44% [54.68] vs. 16.71% [133.45], p = 0.04) and arterial inflammation in active slices (ΔTBRAS = -0.24 [95% CI: -0.46, -0.01], p = 0.04).


The findings of this study demonstrates that in stable atherosclerosis, 12 weeks of treatment with BMS-582949 did not reduce arterial inflammation or hs-CRP compared to placebo, whereas intensification of statin therapy significantly decreased arterial inflammation.



Atherosclerosis; FDG; Imaging; Inflammation; MAPK

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