The sPLA2 Inhibition to Decrease Enzyme Release after Percutaneous Coronary Intervention (SPIDER-PCI) trial.

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<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.

CLINICAL TRIAL REGISTRATION

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00533039.