title: The sPLA2 Inhibition to Decrease Enzyme Release after Percutaneous Coronary Intervention (SPIDER-PCI) trial.
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.
  
  
  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<0.001).
  
  
  CONCLUSIONS
  Inhibition of sPLA(2) by varespladib administered for 3 to 5 days before the procedure does not reduce periprocedural myonecrosis associated with elective percutaneous coronary intervention.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00533039.
authors.affiliation: Interventional Cardiology Program, Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada. vlad.dzavik@uhn.on.ca
authors.forename: Vladimír
authors.initials: V
authors.lastname: Džavík
authors.forename: Shahar
authors.initials: S
authors.lastname: Lavi
authors.forename: Kevin
authors.initials: K
authors.lastname: Thorpe
authors.forename: Paul M
authors.initials: PM
authors.lastname: Yip
authors.forename: Sylvain
authors.initials: S
authors.lastname: Plante
authors.forename: Douglas
authors.initials: D
authors.lastname: Ing
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Overgaard
authors.forename: Mark D
authors.initials: MD
authors.lastname: Osten
authors.forename: Julie
authors.initials: J
authors.lastname: Lan
authors.forename: Kim
authors.initials: K
authors.lastname: Robbins
authors.forename: Steven E
authors.initials: SE
authors.lastname: Miner
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horlick
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Cantor
mesh_terms: D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use*; D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D000368:Aged; D017130:Angioplasty / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007651:Keto Acids; D008297:Male; D008875:Middle Aged; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism*
chemical_list: D000085:Acetates; D015415:Biomarkers; D004791:Enzyme Inhibitors; D007211:Indoles; D007651:Keto Acids; C117948:varespladib; D054497:Phospholipases A2, Secretory