Short-term effect of cycloxygenase-2 inhibition on vascular endothelium and oxidative damage of patients with acute coronary syndrome without ST elevation

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 when administered in these patients. 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 marker, were measured within 24 hours 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=22) or placebo (n=21) orally once daily. There were no differences in the incidence of acute cardiac events between the 2 groups during 30 days of follow-up.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 one 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 syste