Abstract 3084: Early Treatment with Simvastatin in Myocardial Infarction to Reduce the Levels of Multiple Inflammatory Markers in 6-Month Follow-up. FLAME Randomized Clinical Trial
The elevated levels of inflammatory markers have prognostic value in patients with acute coronary syndromes. The use of statins was shown to inhibit the inflammatory response and improve outcome in ACS. The aim of the study:
evaluation of the influence of simvastatin administered early (< 12 hours) after AMI on plasma levels of IL-18, IL-10, MCP-1, soluble CD40 ligand, TNF-alpha, hsCRP and activity of cathepsin G in 6-month follow-up;
to compare two doses of simvastatin (20 and 40mg/d);
to determine whether the effect of simvastatin on inflammatory markers is depentent on reduction of LDL-C levels.
PATIENTS AND METHODS: 82 patients with STEMI admitted for primary PCI < 12 hours after symptoms onset, not treated previously with statins were enrolled. Patients were randomized to receive either 20mg (n=45) or 40mg (n=37) of simvastatin daily. The cytokine levels were measured on admission, after 1 and 6 months using high sensitivity ELISA.
RESULTS: AMI is associated with significant increase of hsCRP, IL-18, MCP-1, sCD40L, TNF-alpha and cathepsin G and low levels of IL-10 in comparison to patients with stable CAD and healthy controls. The baseline number of monocytes was significantly positively correlated with TNF-alpha levels, whereas MCP-1 and TNF-alpha were positively correlated with leukocyte count and fibrinogen levels. Simvastatin Tx reduced the hsCRP levels after 1 and 6 mo., and higher dose [40 mg daily] was more effective than 20mg daily in reducing hsCRP levels. Both treatment groups had significant reduction of IL-10, sCD40L, IL-18, MCP-1 and cathepsin G after 1 and 6 mo. and TNF-alpha after 6 mo. in comparison to baseline. 40 mg daily dose was associated with more marked reduction of sCD40L, IL-10 levels at 1 and 6 mo, IL-18 and cathepsin G at 1 mo. and TNF-alpha at 6 mo. in comparison to lower dose of 20 mg daily. Reductions of inflammatory markers was independent on lowering of LDL levels.
CONCLUSION: Simvastatin treatment initiated within 12 hours after symptoms onset in AMI significantly reduces elevated plasma levels of inflammatory cytokines and activity of cathepsin G in 6-month follow-up independently of reduction of LDL-cholesterol. Higher dose of simvastatin is more effective in reducing inflammatory markers than lower dose.