Abstract 11176: Anti-Inflammatory Effects of Varespladib in Diabetic Patients With Acute Coronary Syndromes
Background: Circulating levels of secretory phospholipase A2 (sPLA2-IIA) have also been shown to predict cardiovascular events both in subjects with and without known coronary heart disease. The activity of sPLA2 activity is increased in diabetes patients; however the effect of sPLA2 inhibition on cardiovascular biomarkers in acute coronary syndrome (ACS) patients has not been investigated. We hypothesize that the anti-inflammatory effects of sPLA2 inhibition in diabetes patients will be greater than non-diabetes patients.
Methods: FRANCIS was a placebo-controlled trial that examined the effects of the sPLA2 inhibitor varespladib 500 mg daily and placebo on biomarkers that are predictive of cardiovascular events at 8 weeks (LDL-C, hs-CRP, IL-6 and sPLA2-IIA) and major cardiovascular events (unstable angina, non-fatal myocardial infarction, non-fatal stroke, death). 624 ACS patients treated with atorvastatin 80 mg daily and other standard of care secondary preventive therapies for a minimum of 6 months. This analysis reports the effects of varespladib in the diabetes subjects (n=171, 27.4% entire cohort).
Results: By 2 weeks, sPLA2-IIA levels were reduced by 80–85% in varespladib patients either with or without diabetes, whereas no reduction was seen in placebo-treated patients (p<0.0001). Among subjects with diabetes, hs-CRP levels decreased more in varespladib-treated patients compared to non-diabetes subjects at 2 (59% vs. 27%, p=0.0004), 4 (83% vs. 63%, p=0.0013), 8 (83% vs. 64%, p=0.030), and 16 weeks (84% vs. 81%%, p=0.078). A similar pattern was seen for IL-6 levels during the early weeks of treatment. In diabetic patients, the reduction with varespladib compared to placebo was significant at week 2 (22% vs. +4%, p=0.0019) and week 4 (47% vs. 24%, p=0.026). The decrease in mean LDL-C was greater in varespladib-treated patients compared to controls, both among those with (39% vs. 32.1%, p<0.03) and without diabetes (45% vs. 40%, p<0.001).
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.
- © 2010 by American Heart Association, Inc.