To assess the impact of combined treatment with simvastatin and ezetimibe or treatment with simvastatin only on lipoprotein-associated phospholipase A2 mass level in patients with coronary heart disease. One hundred patients with angiographically documented coronary atherosclerosis took part in the investigation. Lp-PLA2 mass level and cholesterol fractions were determined at baseline and after 6 months of treatment. Lp-PLA2 mass was determined by PLAC Test; DiaDexus, Inc. Combined treatment with ezetimibe and simvastatin led to significantly greater declines in Lp-PLA2 and lipid profile compared with treatment only with simvastatin (P<0.05). Combination therapy with ezetimibe and simvastatin 20mg/day proved to be as effective as monotherapy with simvastatin 80mg/day on the effect on Lp-PLA2 mass level and lipids (P<0.05). Lp-PLA2 mass level was initially higher in patients with three-vessel coronary artery disease, compared with patients with one-vessel coronary artery disease while baseline levels of lipids and hs-CRP did not differ significantly. Combined treatment, using half the dose of simvastatin, led to greater reduction of Lp-PLA2 mass level total cholesterol and LDL-C, compared to monotherapy with simvastatin. Due to the steady decline of target levels of LDL-C, which leads to prescribing high doses of statins (and it is not always possible because of the presence of co-morbidities), combination therapy with statin and ezetimibe is a reliable alternative, which allows not only to largely reduce LDL-C but also to significantly reduce such important participants of atherosclerosis process and markers of inflammation, as Lp-PLA2 and CRP.