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

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.