Randomized trial of an inhibitor of secretory phospholipase A2 on atherogenic lipoprotein subclasses in statin-treated patients with coronary heart disease.

Abstract:

AIMS:To investigate the effects of secretory phospholipase A2 (sPLA(2)) inhibition on plasma lipoproteins. Secretory phospholipase A2 isoenzymes promote atherosclerosis by mechanisms that include lipoprotein modification, retention, and oxidation. METHODS AND RESULTS:Phospholipase Levels And Serological Markers of Atherosclerosis II (PLASMA II) is a Phase II, randomized, double-blind, placebo-controlled parallel-arm study of two once-daily doses of the novel sPLA(2) inhibitor, 1-H-indole-3-glyoxamide or varespladib methyl (Anthera Pharmaceuticals, Hayward, CA, USA). One hundred and thirty-five stable coronary heart disease patients were treated with either varespladib methyl 250 mg once daily, varespladib methyl 500 mg once daily, or placebo for 8 weeks. Varespladib methyl treatment resulted in statistically significant dose-dependent reductions that were different from placebo in sPLA(2) concentration, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (HDL) cholesterol. When compared with placebo, varespladib methyl 500 mg once daily reduced LDL cholesterol by 15% (P < 0.001), non-HDL cholesterol by 15% (P < 0.001), total very LDL (VLDL) particle concentration by 14% (P = 0.022), and small VLDL particle concentration by 24% (P = 0.030). Relative to baseline, varespladib methyl 500 mg once daily reduced total LDL particle concentration (7%, P = 0.002) and small LDL particle concentration (11%, P = 0.014). CONCLUSION:Reductions in atherogenic lipoproteins suggest that varespladib methyl 500 mg once daily may be an effective anti-atherosclerotic agent. Trial registered at ClinicalTrials.gov, identifier: NCT00525954.

journal_name

Eur Heart J

journal_title

European heart journal

authors

Rosenson RS,Elliott M,Stasiv Y,Hislop C,PLASMA II Investigators.

doi

10.1093/eurheartj/ehq374

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

999-1005

issue

8

eissn

0195-668X

issn

1522-9645

pii

ehq374

journal_volume

32

pub_type

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