varespladib-methyl and Inflammation

The high risk of recurrent cardiovascular events amongst patients with cardiovascular disease receiving evidence-based therapies has prompted investigations into complimentary treatments that may reduce residual risk. Analyses of clinical trials in statin-treated patients demonstrate that elevated lipid levels and an activated systemic inflammatory state are associated with a higher risk of recurrent cardiovascular events.. This article reviews evidence supporting the causal role for secretory phospholipase A(2) (sPLA(2)) in experimental atherosclerosis, the involvement of various sPLA(2) isozymes as mediators of pro-atherogenic lipoprotein remodeling and participants in vascular and systemic inflammatory responses, and the evidence that sPLA(2) inhibition reduces atherosclerosis in experimental models and biomarkers associated with cardiovascular events in coronary heart disease (CHD) patients.. The experimental basis for sPLA(2) inhibition with varespladib methyl as a potential candidate for lowering recurrent cardiovascular events particularly in acute coronary syndrome patients is discussed.. Varespladib methyl therapy reduces atherogenic lipoprotein concentrations and systemic inflammatory markers in CHD patients. The future role of varespladib methyl in CHD patients awaits the results of ongoing clinical trials.

Topics: Acetates; Animals; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Cholesterol, LDL; Clinical Trials as Topic; Coronary Disease; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Humans; Indoles; Inflammation; Keto Acids; Male; Phospholipases A2, Secretory

The action of secretory phospholipase A(2) (sPLA(2)) on lipoproteins may render them more susceptible to oxidation, thereby promoting vascular inflammation and increasing cardiovascular risk. Patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events that is associated with biomarkers of inflammation, including sPLA(2). The Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 Weeks (VISTA-16, NCT01130246) tests the hypothesis that varespladib methyl, an inhibitor of several sPLA(2) isoforms with a causal role in atherosclerosis, reduces cardiovascular risk among patients with acute coronary syndromes.. Up to 6,500 patients with acute coronary syndrome will be randomized to receive treatment with varespladib methyl 500 mg daily or placebo for 16 weeks, in addition to background treatment with atorvastatin and other evidence-based therapies. The primary efficacy parameter is the combination of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for unstable angina with objective evidence of myocardial ischemia. Effects of varespladib methyl on lipid and inflammatory markers, in addition to safety and tolerability, will also be evaluated.. sPLA(2) inhibition has the potential to exert a favorable effect on the artery wall. The VISTA-16 study will determine whether varespladib methyl has a beneficial impact on cardiovascular events in patients with an acute coronary syndrome.

Topics: Acetates; Acute Coronary Syndrome; Atorvastatin; Double-Blind Method; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Inflammation; Keto Acids; Phospholipases A2, Secretory; Pyrroles