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.
RCT Entities:
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.
Authors: Risto Kerkelä; Matthieu Boucher; Raihana Zaka; Erhe Gao; David Harris; Jarkko Piuhola; Jianliang Song; Raisa Serpi; Kathleen C Woulfe; Joseph Y Cheung; Eileen O'Leary; Joseph V Bonventre; Thomas Force Journal: Clin Transl Sci Date: 2011-08 Impact factor: 4.689
Authors: Michael V Holmes; Tabassome Simon; Holly J Exeter; Lasse Folkersen; Folkert W Asselbergs; Montse Guardiola; Jackie A Cooper; Jutta Palmen; Jaroslav A Hubacek; Kathryn F Carruthers; Benjamin D Horne; Kimberly D Brunisholz; Jessica L Mega; Erik P A van Iperen; Mingyao Li; Maarten Leusink; Stella Trompet; Jeffrey J W Verschuren; G Kees Hovingh; Abbas Dehghan; Christopher P Nelson; Salma Kotti; Nicolas Danchin; Markus Scholz; Christiane L Haase; Dietrich Rothenbacher; Daniel I Swerdlow; Karoline B Kuchenbaecker; Eleonora Staines-Urias; Anuj Goel; Ferdinand van 't Hooft; Karl Gertow; Ulf de Faire; Andrie G Panayiotou; Elena Tremoli; Damiano Baldassarre; Fabrizio Veglia; Lesca M Holdt; Frank Beutner; Ron T Gansevoort; Gerjan J Navis; Irene Mateo Leach; Lutz P Breitling; Hermann Brenner; Joachim Thiery; Dhayana Dallmeier; Anders Franco-Cereceda; Jolanda M A Boer; Jeffrey W Stephens; Marten H Hofker; Alain Tedgui; Albert Hofman; André G Uitterlinden; Vera Adamkova; Jan Pitha; N Charlotte Onland-Moret; Maarten J Cramer; Hendrik M Nathoe; Wilko Spiering; Olaf H Klungel; Meena Kumari; Peter H Whincup; David A Morrow; Peter S Braund; Alistair S Hall; Anders G Olsson; Pieter A Doevendans; Mieke D Trip; Martin D Tobin; Anders Hamsten; Hugh Watkins; Wolfgang Koenig; Andrew N Nicolaides; Daniel Teupser; Ian N M Day; John F Carlquist; Tom R Gaunt; Ian Ford; Naveed Sattar; Sotirios Tsimikas; Gregory G Schwartz; Debbie A Lawlor; Richard W Morris; Manjinder S Sandhu; Rudolf Poledne; Anke H Maitland-van der Zee; Kay-Tee Khaw; Brendan J Keating; Pim van der Harst; Jackie F Price; Shamir R Mehta; Salim Yusuf; Jaqueline C M Witteman; Oscar H Franco; J Wouter Jukema; Peter de Knijff; Anne Tybjaerg-Hansen; Daniel J Rader; Martin Farrall; Nilesh J Samani; Mika Kivimaki; Keith A A Fox; Steve E Humphries; Jeffrey L Anderson; S Matthijs Boekholdt; Tom M Palmer; Per Eriksson; Guillaume Paré; Aroon D Hingorani; Marc S Sabatine; Ziad Mallat; Juan P Casas; Philippa J Talmud Journal: J Am Coll Cardiol Date: 2013-07-31 Impact factor: 24.094