title: 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.
abstract: 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.
authors: Division of Cardiology, Hotel Dieu de France Hospital and Saint Joseph University School of Medicine, Beirut, Lebanon.
authors: Mireille
authors: M
authors: Azar
authors: Emmanuel
authors: E
authors: Valentin
authors: Georges
authors: G
authors: Badaoui
authors: Roland
authors: R
authors: Kassab
authors: Antoine
authors: A
authors: Sarkis
authors: Rabih R
authors: RR
authors: Azar
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D001384:Azetidines / Q000008:administration & dosage*; D008078:Cholesterol, LDL / Q000187:drug effects*; D003324:Coronary Artery Disease; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054497:Phospholipases A2, Secretory / Q000378:metabolism*; D011758:Pyrroles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D054497:Phospholipases A2, Secretory; D000069438:Ezetimibe