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Synergistic Anti-inflammatory Effect with Pioglitazone and Simvastatin

May 8, 2014

Pioglitazone and simvastatin combined may have a positive effect on atherosclerosis…. 

In this study, researchers assessed the anti-inflammatory action of simvastatin and pioglitazone on epicardial adipose tissue — a known source of inflammatory cytokines — in patients with coronary artery disease and metabolic syndrome.

Researchers assigned 73 patients with multivessel CAD to 1 of 4 subgroups: Control group (n = 17), simvastatin 20 mg per day (n = 20), pioglitazone 15 mg or 30 mg per day (n = 18), and simvastatin 20 mg per day plus pioglitazone 30 mg/day (n = 18).

During surgery epicardial adipose tissue samples were obtained and the infiltration of macrophages and lymphocytes as well as cytokine secretion was investigated. These findings were then compared to plasma inflammatory biomarkers.

Simvastatin monotherapy had a significant effect on reducing plasma interleukin-6, leptin, resistin and monocyte chemoattractant protein-1 (P < 0.001). Pioglitazone monotherapy reduced interleukin-6, tumoral necrose factor-alpha (TNF-α), resistin and matrix metalloproteinase-9 (P < 0.001). When compared to the control group, simvastatin combined with pioglitazone yielded a further reduction in variables including interleukin-6, TNF-α, resistin, asymmetric dimethylarginine and metalloproteinase-9 (P < 0.001). Further, higher levels of plasma adiponectin and lower high sensitivity C-reactive protein levels were found in the combined treatment group.

A positive correlation between the average percentage systemic and tissue cytokines was found following treatments as well as between serum hsCRP and the percentage of macrophages in epicardial adipose tissue.

Negative correlations were found in TNF-α after treatment with simvastatin (r = -0.025, P = 0.33) and leptin after treatment with pioglitazone (r = -0.877, P < 0.0001).

No correlations among plasma lipid variables and tissue inflammatory variables were observed.

Practice Pearls:
  • Pioglitazone, simvastatin or a combination of the two may reduce epicardial adipose tissue and plasma inflammatory markers
  • Using a combination of pioglitazone and simvastatin may have a synergistic effect on controlling the progression of atherosclerosis
  • Larger studies are needed to confirm these findings and the possible clinical implications

Grosso AF, De oliveira SF, Higuchi Mde L, Favarato D, Dallan LA, Da luz PL. Synergistic anti-inflammatory effect: simvastatin and pioglitazone reduce inflammatory markers of plasma and epicardial adipose tissue of coronary patients with metabolic syndrome. Diabetol Metab Syndr. 2014;6(1):47. http://www.dmsjournal.com/content/6/1/47