Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles, apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia

被引:67
作者
Maki, Kevin C. [1 ]
Bays, Harold E. [2 ]
Dicklin, Mary R. [1 ]
Johnson, Susan L. [3 ]
Shabbout, Mayadah [3 ]
机构
[1] Biofortis N Amer, Provident Clin Res, Glen Ellyn, IL 60137 USA
[2] Louisville Metab & Atherosclerosis Res Ctr, Louisville, KY USA
[3] GlaxoSmithKline, Res Triangle Pk, NC USA
关键词
Apolipoprotein CIII; Lipoprotein-associated phospholipase A(2); Lipoprotein particles; Omega-3 fatty acids; Statins; Triglycerides; LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; DIETARY FISH-OIL; COMBINED HYPERLIPIDEMIA; CARDIOVASCULAR-DISEASE; RICH LIPOPROTEINS; ARTERY-DISEASE; SIMVASTATIN; 20; FATTY-ACIDS; RISK;
D O I
10.1016/j.jacl.2011.09.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
BACKGROUND: Prescription omega-3-acid ethyl esters (POM3) reduce triglycerides (TG) and very low-density lipoprotein cholesterol and increase high-density lipoprotein cholesterol (HDL-C) in patients with hypertriglyceridemia. OBJECTIVE: To examine the effects of POM3 plus atorvastatin versus placebo plus atorvastatin on lipoprotein particle concentrations and sizes, apolipoprotein (Apo) CIII, and lipoprotein-associated phospholipase A(2) mass in subjects with mixed dyslipidemia. METHODS: After a 4-week diet lead in, men and women with non-HDL-C >160 mg/dL and TG 250-599 mg/dL, while taking no lipid-altering drugs, received double-blind 4 g/d POM3 (n = 118) or placebo (n = 119) with open-label atorvastatin 10 mg/d for 8 weeks, followed by escalation to 20 mg/d atorvastatin for 4 weeks, then 40 mg/d atorvastatin for 4 weeks. RESULTS: Total low-density lipoprotein particle (LDL-P) concentration decreased significantly from baseline, and the reductions did not differ between the POM3 and placebo groups (-659.7 vs -624.4 nmol/L, P = .181). With POM3, compared with placebo, small LDL-P concentration decreased (P = .026), large LDL-P concentration increased (P < .001), mean LDL-P size increased (P = .001), a larger fraction of subjects switched from LDL subclass pattern B to A, and Apo CIII and lipoprotein-associated phospholipase A(2) levels were reduced (P < .001). The incremental effects of POM3 were similar across atorvastatin closes for most variables. CONCLUSION: This analysis supports the view that LDL-P concentration is not increased by POM3 plus atorvastatin, relative to atorvastatin monotherapy, and is associated with potentially favorable shifts in LDL-P subtractions, Apo CIII and lipoprotein-associated phospholipase A(2) in mixed dyslipidemia. (C) 2011 National Lipid Association. All rights reserved.
引用
收藏
页码:483 / 492
页数:10
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