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Divergent effects of rofecoxib on endothelial function and inflammation in acute coronary syndromes
John P Lekakis1, Georgia Vamvakou, Ioanna Andreadou
1Vascular Laboratory, Department of Clinical Therapeutics, Alexandra University Hospital, 12 Iridanou str., Athens 11528, Greece.
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.
Insights
Rofecoxib reduced inflammation and oxidative stress in acute coronary syndrome patients but did not improve endothelial function. This suggests potential cardiovascular risks associated with cyclooxygenase-2 inhibitors.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Selective cyclooxygenase-2 (COX-2) inhibitors raise concerns regarding cardiovascular safety.
- Previous studies indicate an increased risk of cardiac events with COX-2 inhibitors.
Purpose of the Study:
- To evaluate the short-term effects of rofecoxib on endothelial function, oxidative damage, and inflammation.
- To assess these effects in patients with acute coronary syndromes without ST-segment elevation.
Main Methods:
- 43 patients with acute coronary syndromes were randomized to receive rofecoxib or placebo with aspirin for one week.
- Measurements included flow-mediated dilatation (FMD), nitrate-mediated dilatation (NMD), malondialdehyde, C-reactive protein, and interleukin-6.
Main Results:
- Rofecoxib significantly reduced malondialdehyde, C-reactive protein, and interleukin-6 levels.
- No significant changes were observed in the placebo group for these markers.
- No statistically significant differences in FMD or NMD were found between the rofecoxib and placebo groups.
Conclusions:
- Rofecoxib, when co-administered with aspirin, reduced inflammatory and oxidative markers.
- Endothelial function, assessed by FMD and NMD, did not improve.
- The lack of endothelial function improvement warrants consideration of potential adverse cardiovascular effects of COX-2 inhibition.
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