Divergent effects of rofecoxib on endothelial function and inflammation in acute coronary syndromes.
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.
Lekakis
John P
JP
Vascular Laboratory, Department of Clinical Therapeutics, Alexandra University Hospital, 12 Iridanou str., Athens 11528, Greece.
Vamvakou
Georgia
G
Andreadou
Ioanna
I
Ganiatsos
George
G
Karatzis
Emmanouil
E
Protogerou
Athanassios
A
Papaioannou
Theodore
T
Ikonomidis
Ignatios
I
Papamichael
Christos
C
Mavrikakis
Myron E
ME
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*
D052246:Cyclooxygenase 2 Inhibitors; D015850:Interleukin-6; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D008315:Malondialdehyde; D002097:C-Reactive Protein