The sPLA 2 Inhibition to Decrease Enzyme Release After Percutaneous Coronary Intervention (SPIDER-PCI) Trial
Open Access
- 7 December 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 122 (23), 2411-2418
- https://doi.org/10.1161/circulationaha.110.950733
Abstract
Background—: Secretory phospholipase A 2 (sPLA 2 ) may play a role in myonecrosis after elective percutaneous coronary intervention (PCI). Inhibition of this enzyme may have a beneficial effect. The central hypothesis of this study was that treatment with varespladib, a small-molecule inhibitor of sPLA 2 would reduce postprocedural release of cardiac biomarkers after elective percutaneous coronary intervention. Methods and Results—: Between October 2007 and June 2009, 144 stable patients were randomized in a phase II trial to receive varespladib 500 mg PO BID or placebo 3 to 5 days before and for 5 days after elective percutaneous coronary intervention. The primary end point was elevation of troponin I or creatine kinase-MB above the upper limit of normal at 6 to 8 or 18 to 24 hours after percutaneous coronary intervention. Mean age was 63±10 and 64±10 years, with 38% and 42% with diabetes mellitus and 29% and 28% with prior myocardial infarction for the varespladib and placebo groups, respectively. The primary end point occurred in 75% of varespladib and 63% of placebo patients ( P =0.14). Troponin I 3 times the upper limit of normal was observed in 57% and 50% ( P =0.39) and creatine kinase-MB 2 times the upper limit of normal in 14% and 3% ( P =0.018). Median (first and third quartiles) change in high-sensitivity C-reactive protein in these 2 groups was 0.65 mg/L (−0.18 and 1.48) and 0.70 mg/L (0.00 and 1.50) at 18 to 24 hours ( P =0.81) and 0.20 mg/L (−0.70 and 1.40) and 0.60 mg/L (−0.12 and 1.72) at 3 to 5 days ( P =0.23), whereas change in sPLA 2 activity at 3 to 5 days in a subset was −2.85 ng/ml (−3.40 and −1.85) and 0.25 ng/ml (−0.20 and 0.85) ( P 2 by varespladib administered for 3 to 5 days before the procedure does not reduce periprocedural myonecrosis associated with elective percutaneous coronary intervention. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00533039.Keywords
This publication has 31 references indexed in Scilit:
- Inhibition of type 2A secretory phospholipase A2 reduces death of cardiomyocytes in acute myocardial infarctionApoptosis, 2009
- Varespladib (A-002), a Secretory Phospholipase A2 Inhibitor, Reduces Atherosclerosis and Aneurysm Formation in ApoE− / − MiceJournal of Cardiovascular Pharmacology, 2009
- Circulating Secretory Phospholipase A2 Activity and Risk of Incident Coronary Events in Healthy Men and WomenArteriosclerosis, Thrombosis, and Vascular Biology, 2007
- Detection and quantification of embolic particles during percutaneous coronary intervention to stable plaque: It correlates to coronary flow dynamics and myocardial damageCatheterization and Cardiovascular Interventions, 2006
- Safety and Efficacy of Short-Term Celecoxib Before Elective Percutaneous Coronary Intervention for Stable Angina PectorisThe American Journal of Cardiology, 2006
- Macrophage-specific expression of group IIA sPLA2 results in accelerated atherogenesis by increasing oxidative stressJournal of Lipid Research, 2005
- Effects of Glycoprotein IIb/IIIa Receptor Inhibition with Tirofiban on Minor Myocardial Damage in Angiographically Successful Percutaneous Coronary AngioplastyJMIR AI, 2004
- Prognostic value and the changes of plasma levels of secretory type II phospholipase A2 in patients with coronary artery disease undergoing percutaneous coronary interventionPublished by Oxford University Press (OUP) ,2003
- Troponin I elevation and cardiac events after percutaneous coronary interventionAmerican Heart Journal, 2003
- Frequency and long-term impact of myonecrosis after coronary stentingPublished by Oxford University Press (OUP) ,2002