Effectiveness and tolerability of early initiation of combined lipid-lowering therapy included simvastatin and fenofibrate vs simvastatin alone in patients with acute coronary syndrome and type 2 diabetes mellitus with hypertriglyceridemia

The aim – to determine the effect of early statin-fibrate combination therapy on correction of atherogenic dyslipidemia and apoprotein metabolism in acute coronary syndrome (ACS) patients with type 2 diabetes mellitus. Materials and methods. Patients (n=60) with T2DM, hypertriglyceridemia (HTG), were randomly assigned in 5–21 days of onset of any form of ACS to receive a combination of simvastatin 40 mg and fenofibrate 145 mg daily or simvastatin 40 mg daily during 12 months. At 3 and 12 months after randomization, we measured levels of absolute and percent changes in the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non high density lipoprotein cholesterol (Non-HDL-C), TG levels, percentage of patients achieving and retaining complex lipid goals according to ESC 2011 guideline, absolute and percent changes in apoproteins A1 and B (apoA1 and apoB) levels, аpoB/аpoA1 ratio and lipoprotein (a) (Lp(a)), HbA1, uric acid and common safety measurements (ALT/AST, creatinine levels, eGFR). Results and discussion. Nonsignificant TC levels decrease all over the study without intergroup difference (p>0.05) was seen with the same results as for LDL-C levels in both groups. Constant decrease of Non-HDL-C to 2.88 (2.41–3.38) mmol/L with combined treatment (р=0.042 with index level) vs evident tendency to its increase 3.46 (2.87–4.44) mmol/l in the only statin group in 12 months was registered with intergroup difference (р=0.047). The constant greater extent of TG lowering in combined treatment was seen both at 3 months (р=0.037), and at 12 months (р=0.007) with significant intergroup changes: р=0.035 and р=0.03 respectively. Combination therapy has increased аpoA1 to 1.45 (1.29–1.62) g/L (р<0.00001 with initial), decrease аpoB level to 0.87 (0.71–0.97) g/L (p>0.05) and аpoB/аpoA1 relation to 0.57 (0.51–0.74) (р=0.0005 compared to initial). In statin group initial moderate increase of аpoA1 in 3 months changed by its prominent decrease to 1.32 (1.18–1.43) g/L (р=0.02 with initial data), аpoB increase to 0.97 (0.77–1.14) g/L along with ароВ/ароА1 relation 0.74 (0.56–0.87) with intergroup difference ароВ/ароА1 relation (р=0.047) at the study end. Combined therapy provided significant decrease of Lp(a) content compared to initial level all over the study: in 3 months (р=0.0004) and in12 months (р=0.005) unlike slight elevation during the study in simvastatin group (p>0.05). The combined therapy treatment with fenofibrate had led to highly significant decrease of uric acid levels just in 3 months of treatment (р<0.0001 from baseline) and this level withheld all the study period (р=0.002) without any changes in the control group. Combined therapy was associated with slight but significant (р=0.0006) decline of renal function during the study, not seen in the statin group without treatment withdrawal and requirements of replacement therapy. Conclusion. The combined therapy with simvastatin and fenofibrate in patients with type 2 diabetes mellitus and HTG initiated early after ACS for one year period is safe, effectively correctes atherogenic dyslipidemia, normalizes apolipoprotein metabolism and decreases Lp(a), uric acid levels unlike simvastatin therapy alone.