title: After FRANCIS: next steps in the clinical evaluation of varespladib methyl.
abstract: Secretory phospholipase A(2) (sPLA(2)) represents a family of isoenzymes that participate in lipoprotein and inflammatory pathways, mediate atherosclerosis and enhance myocardial ischemic injury. The Fewer Recurrent Acute Coronary Events with Near-term Cardiovascular Inflammatory Suppression (FRANCIS) trial (NCT00743925) was a Phase II trial designed to examine the effects of varespladib methyl, a small-molecule inhibitor of sPLA(2), on plasma biomarkers in patients with acute coronary syndrome (ACS) who were treated with atorvastatin 80 mg and standard-of-care daily. Varespladib methyl significantly reduced low-density lipoprotein cholesterol and inflammatory biomarkers in ACS subjects treated with standard-of-care and atorvastatin 80 mg daily. There was a nonsignificant reduction in major adverse cardiovascular events at study completion; however, positive trends remained for unstable angina and myocardial infarction. In order to achieve the widespread use of varespladib methyl in ACS patients, completion of a prospective, randomized placebo-controlled trial in ACS patients and stable coronary artery disease patients with increased sPLA(2) activity will be required.
authors.affiliation: Mount Sinai School of Medicine, New York, NY 10029, USA. robert.rosenson@mssm.edu
authors.forename: Robert S
authors.initials: RS
authors.lastname: Rosenson
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects; D008078:Cholesterol, LDL / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000627:therapeutic use*; D007651:Keto Acids; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000627:therapeutic use*
chemical_list: D000085:Acetates; D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D007211:Indoles; D007651:Keto Acids; D011758:Pyrroles; C117948:varespladib; D002097:C-Reactive Protein; D000069059:Atorvastatin; D054497:Phospholipases A2, Secretory