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Anti-Inflammatory Effects of Varespladib Methyl in Diabetic Patients with Acute Coronary Syndrome

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Abstract

Purpose

Secretory phospholipase A2 group IIA (sPLA2−IIA) concentration and activity are associated with increased risk of cardiovascular events in acute coronary syndrome (ACS) patients. This study evaluated baseline differences in sPLA2-IIA concentration and other inflammatory markers in ACS patients with and without diabetes, and the inflammatory biomarker response to selective sPLA2 inhibition.

Methods

The effects of the sPLA2 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 sPLA2-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 sPLA2-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.

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Conflicts of interest

Drs. Fraser and Hislop are employees of Anthera Pharmaceuticals and they have ownership interest in Anthera Pharmaceuticals.

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Authors and Affiliations

  1. Mount Sinai School of Medicine, 1425 Madison Ave., New York, NY, 10029, USA

    Robert S. Rosenson

  2. Anthera Pharmaceuticals, Inc., 25801 Industrial Blvd., Suite B, Hayward, CA, 94545, USA

    Heather Fraser & Colin Hislop

  3. Worldwide Clinical Trials, Isaac Newton Centre, Nottingham Science Park, Nottingham, UK, NG7 2RH

    Michael A. Goulder

Authors
  1. Robert S. Rosenson
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  2. Heather Fraser
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  3. Michael A. Goulder
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  4. Colin Hislop
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Correspondence to Robert S. Rosenson.

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Rosenson, R.S., Fraser, H., Goulder, M.A. et al. Anti-Inflammatory Effects of Varespladib Methyl in Diabetic Patients with Acute Coronary Syndrome. Cardiovasc Drugs Ther 25, 539–544 (2011). https://doi.org/10.1007/s10557-011-6344-2

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  • DOI: https://doi.org/10.1007/s10557-011-6344-2

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