Inhibition of sPLA2 and Endothelial Function: A Substudy of the SPIDER-PCI Trial

Background: Inflammation plays an important role in the pathophysiology of atherosclerosis and endothelial dysfunction, and occurs after percutaneous coronary intervention (PCI). We evaluated whether endothelial function is attenuated after PCI and if inhibition of secretory phospholipase A(2) (sPLA(2)) activity augments endothelial function and coronary flow reserve (CFR) in these patients. Methods: In the sPLA(2) Inhibition to Decrease Enzyme Release After Percutaneous Coronary Intervention (SPIDER-PCI) study, patients undergoing elective PCI were randomized to receive Varespladib (Anthera Pharmaceuticals Inc, San Mateo, CA), an inhibitor of sPLA(2), or placebo 3-5 days prior to PCI and for 5 days after PCI. In this substudy, endothelial function was assessed in 31 patients by flow-mediated dilation (FMD) before treatment and on the day after PCI, while taking study medication. During the PCI procedure, CFR was assessed using a Doppler guide wire. Results: Baseline and procedural characteristics were comparable in both groups and sPLA(2) activity was similar at baseline. After PCI, sPLA(2) activity decreased only in the Varespladib group (2.9 +/- 0.9 to 0.5 +/- 0.4 ng/mL), and high-sensitivity C-reactive protein (hsCRP) increased by more than 100% in both groups. FMD at baseline was 3.66 +/- 2.45% (Varespladib) and 3.37 +/- 1.73% (placebo) with nonsignificant increase in both groups after PCI. The effect of Varespladib on FMD, adjusted for pre-PCI FMD by linear regression, was -1.16 +/- 1.68%; P = 0.5. CFR was 2.45 +/- 0.66 and 2.77 +/- 0.85 in the Varespladib and placebo groups, respectively (P = 0.36). Conclusions: Systemic endothelial function is not reduced after elective PCI despite eliciting acute inflammatory response. Acute inhibition of sPLA(2) activity with Varespladib does not affect endothelial or microvascular function after PCI.