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

• Published in: Canadian journal of cardiology Vol. 28; no. 2; pp. 215 - 221
• Main Authors: Lavi, Shahar, MD, Thorpe, Kevin, MMath, Luca, Mary Clare, BSc, Liuni, Andrew, BSc, Floras, John, MD, DPhil, Horlick, Eric M., MD, Ing, Douglas, MD, Osten, Mark D., MD, Overgaard, Christopher B., MD, Lan, Julie, RN, Parker, John D., MD, Cantor, Warren J., MD, Džavík, Vladimír, MD
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01-03-2012
• Subjects: Acetates - pharmacology; Acetates - therapeutic use; Aged; Angioplasty, Balloon, Coronary - adverse effects; Cardiovascular; Coronary Artery Disease - enzymology; Coronary Artery Disease - physiopathology; Coronary Artery Disease - therapy; Coronary Circulation - drug effects; Coronary Vessels - drug effects; Coronary Vessels - enzymology; Coronary Vessels - physiopathology; Endothelium, Vascular - drug effects; Endothelium, Vascular - enzymology; Endothelium, Vascular - physiopathology; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Female; Humans; Indoles - pharmacology; Indoles - therapeutic use; Inflammation - etiology; Inflammation - physiopathology; Male; Middle Aged; Phospholipases A2, Secretory - metabolism; Prospective Studies; Rheology
• ISSN: 0828-282X; 1916-7075
• DOI: 10.1016/j.cjca.2011.11.007

Abstract 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 A2 (sPLA2 ) activity augments endothelial function and coronary flow reserve (CFR) in these patients. Methods In the sPLA2 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 sPLA2 , 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 sPLA2 activity was similar at baseline. After PCI, sPLA2 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 sPLA2 activity with Varespladib does not affect endothelial or microvascular function after PCI.