Comparison of the effects of combination atorvastatin (40 mg) + ezetimibe (10 mg) versus atorvastatin (40 mg) alone on secretory phospholipase A2 activity in patients with stable coronary artery disease or coronary artery disease equivalent

Secretory phospholipase A2 (sPLA2) is an enzyme that plays an important role in the pathogenesis of atherosclerosis and of adverse cardiovascular events. It is currently the target of emerging therapeutic agents. Our study was designed to investigate the effect of aggressive lowering of low-density lipoprotein (LDL) cholesterol with ezetimibe and atorvastatin on sPLA2 activity. We randomized 100 patients with stable coronary artery disease (CAD) or CAD equivalent (diabetes, stroke, or peripheral vascular disease) to receive ezetimibe 10 mg/day in association with atorvastatin 40 mg/day (combination therapy group) versus atorvastatin 40 mg/day and placebo (monotherapy group). Patients on statin therapy before inclusion were allowed to enter the study as long as the potency of the statin was lower than atorvastatin 40 mg/day. Lipid profile, high-sensitivity C-reactive protein (hs-CRP), and sPLA activity were measured at baseline and after 8 weeks of therapy. The decrease in LDL cholesterol was more significant in the combination therapy group, but the decrease in hs-CRP was similar. sPLA2 activity significantly decreased in the ezetimibe/atorvastatin group from 29 U/ml (interquartile range 23 to 35) to 26 U/ml (23 to 29, p = 0.001) but remained similar in the placebo/atorvastatin group (23 U/ml, 19 to 32, vs 22 U/ml, 19 to 28, p = NS). In a multivariate stepwise linear regression model, change in sPLA2 correlated with change in hs-CRP (p <0.001), baseline LDL cholesterol level (p = 0.001), body mass index (p = 0.003), diabetes mellitus (p = 0.04) and combination therapy with ezetimibe/atorvastatin (p = 0.05). In conclusion, this study demonstrates that coadministration of ezetimibe and atorvastatin decreases sPLA2 activity.