title: Divergent effects of rofecoxib on endothelial function and inflammation in acute coronary syndromes.
abstract: BACKGROUND
  The safe use of selective inhibitors of cyclooxygenase-2 in patients with cardiovascular disease has been questioned because of studies showing an increased risk of cardiac events. We examined the short-term effect of rofecoxib, a selective cyclooxygenase-2 inhibitor, on endothelial function, oxidative damage and inflammation in patients with acute coronary syndromes without ST-segment elevation.
  
  
  METHODS
  Forty-three patients with acute coronary syndromes without ST-segment elevation participated in the study. Flow-mediated dilatation (FMD), nitrate-mediated dilatation (NMD) of the brachial artery, malondialdehyde, a marker of lipid peroxidation, C-reactive protein, an acute phase marker of inflammation, and interleukin-6, a proinflammatory cytokine, were measured within 24 h of admission and a week later. Patients were randomized to receive for a week 100 mg aspirin daily with either 25 mg of rofecoxib (n=21) or placebo (n=22) orally once daily.
  
  
  RESULTS
  Malondialdehyde, C-reactive protein and interleukin-6 levels were reduced in the rofecoxib group (p=0.04, p=0.003 and p=0.02 respectively) while they remained unchanged in the placebo group after 1 week of treatment. FMD and NMD changes in both groups were not statistically different.
  
  
  CONCLUSIONS
  Co-administration of rofecoxib with low-dose aspirin decreases inflammatory and oxidative indices but does not improve endothelial function. The lack of improvement in FMD despite the improvement in inflammation and oxidative stress could be viewed in association to the recent observations on the adverse effects of COX-2 inhibition on the cardiovascular system.
authors.affiliation: Vascular Laboratory, Department of Clinical Therapeutics, Alexandra University Hospital, 12 Iridanou str., Athens 11528, Greece.
authors.forename: John P
authors.initials: JP
authors.lastname: Lekakis
authors.forename: Georgia
authors.initials: G
authors.lastname: Vamvakou
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreadou
authors.forename: George
authors.initials: G
authors.lastname: Ganiatsos
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Karatzis
authors.forename: Athanassios
authors.initials: A
authors.lastname: Protogerou
authors.forename: Theodore
authors.initials: T
authors.lastname: Papaioannou
authors.forename: Ignatios
authors.initials: I
authors.lastname: Ikonomidis
authors.forename: Christos
authors.initials: C
authors.lastname: Papamichael
authors.forename: Myron E
authors.initials: ME
authors.lastname: Mavrikakis
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000503:physiopathology / Q000628:therapy; D002097:C-Reactive Protein / Q000032:analysis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007783:Lactones / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects; D011446:Prospective Studies; D012307:Risk Factors; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D015850:Interleukin-6; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D008315:Malondialdehyde; D002097:C-Reactive Protein