Anti-inflammatory effects of varespladib methyl in diabetic patients with acute coronary syndrome.

Abstract

PURPOSE:

Secretory phospholipase A(2) group IIA (sPLA(2-)IIA) concentration and activity are associated with increased risk of cardiovascular events in acute coronary syndrome (ACS) patients. This study evaluated baseline differences in sPLA(2)-IIA concentration and other inflammatory markers in ACS patients with and without diabetes, and the inflammatory biomarker response to selective sPLA(2) inhibition.

METHODS:

The effects of the sPLA(2) inhibitor varespladib methyl 500 mg daily and placebo on serial changes in inflammatory and lipid biomarkers were examined in 624 ACS patients who were treated with standard of care including atorvastatin 80 mg daily.

RESULTS:

Compared with non-diabetic patients, diabetic patients had higher baseline concentrations of sPLA(2)-IIA (p = 0.0066), hs-CRP (p = 0.0155), and IL-6 (p = 0.009). At 8 weeks of treatment (primary endpoint), varespladib methyl reduced median sPLA(2)-IIA levels by -83.6% in diabetic patients and by -82.4% in non-diabetic patients (p = 0.33). Median hs-CRP and IL-6 levels were reduced in both varespladib methyl-treated diabetic and non-diabetic patients, but these differences were not statistically significantly different at 8 weeks (p = 0.57 and p = 0.97 respectively).

CONCLUSIONS:

Varespladib significantly reduces the post-ACS inflammatory response in those with and without diabetes. These responses were greater in diabetic subjects compared to non-diabetic subjects.

• Authors: Robert S Rosenson, Heather Fraser, Michael A Goulder, Colin Hislop
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 25 Issue 6 Pg. 539-44 (Dec 2011) ISSN: 1573-7241 [Electronic] United States
• PMID: 21989792 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Acetates
• Anti-Inflammatory Agents
• Biomarkers
• Heptanoic Acids
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Indoles
• Interleukin-6
• Keto Acids
• Pyrroles
• varespladib methyl
• C-Reactive Protein
• Atorvastatin
• Group II Phospholipases A2

Topics

• Acetates (administration & dosage, therapeutic use)
• Acute Coronary Syndrome (complications, drug therapy, immunology)
• Anti-Inflammatory Agents (administration & dosage, therapeutic use)
• Atorvastatin
• Biomarkers (analysis, blood)
• C-Reactive Protein (analysis)
• Diabetes Mellitus, Type 2 (complications, drug therapy, immunology)
• Drug Therapy, Combination
• Female
• Group II Phospholipases A2 (antagonists & inhibitors, blood)
• Heptanoic Acids (administration & dosage, therapeutic use)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, therapeutic use)
• Indoles (administration & dosage, therapeutic use)
• Interleukin-6 (blood)
• Keto Acids
• Male
• Middle Aged
• Pyrroles (administration & dosage, therapeutic use)
• Treatment Outcome