Inhibition of secretory phospholipase A(2) in patients with acute coronary syndromes: rationale and design of the vascular inflammation suppression to treat acute coronary syndrome for 16 weeks (VISTA-16) trial.

Abstract

BACKGROUND:

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.

METHODS:

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.

CONCLUSION:

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.

• Authors: Stephen J Nicholls, Matthew A Cavender, John J P Kastelein, Gregory Schwartz, David D Waters, Robert S Rosenson, Dianna Bash, Colin Hislop
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 26 Issue 1 Pg. 71-5 (Feb 2012) ISSN: 1573-7241 [Electronic] United States
• PMID: 22109255 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Acetates
• Heptanoic Acids
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Indoles
• Keto Acids
• Pyrroles
• varespladib methyl
• Atorvastatin
• Phospholipases A2, Secretory

Topics

• Acetates (therapeutic use)
• Acute Coronary Syndrome (drug therapy)
• Atorvastatin
• Double-Blind Method
• Heptanoic Acids (therapeutic use)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Indoles (therapeutic use)
• Inflammation (drug therapy)
• Keto Acids
• Phospholipases A2, Secretory (antagonists & inhibitors)
• Pyrroles (therapeutic use)