Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction and inflammatory markers in patients with coronary artery disease.
OBJECTIVE
The aim of this study was to determine whether selective cyclooxygenase-2 (COX-2) inhibition with rofecoxib can modulate endothelial dysfunction and levels of circulating inflammatory markers in patients with established coronary artery disease (CAD).


BACKGROUND
Expression of COX-2 is upregulated in atherosclerosis. Thus, it has been hypothesized that COX-2 may contribute to atherogenesis by producing eicosanoids, which mediate vascular inflammation and endothelial dysfunction.


METHODS
In a randomized, double-blind, placebo-controlled, parallel-design trial, we studied the vascular effects of rofecoxib on brachial artery vasoreactivity and inflammatory markers in 60 patients with angiographically proven CAD who were taking concomitant low-dose aspirin. Patients were randomly assigned to receive either rofecoxib (25 mg/day; n = 30) or placebo (n = 30) for eight weeks. Brachial artery endothelium-dependent flow-mediated dilation (FMD), endothelium-independent nitroglycerin-mediated dilation (NMD), and inflammatory markers (i.e., high-sensitivity C-reactive protein [CRP], soluble intercellular adhesion molecule-1 [sICAM-1], and soluble interleukin-6 receptor [sIL-6r]) were measured at baseline and after eight-week follow-up.


RESULTS
Baseline clinical characteristics were similar in the two groups. After eight weeks of treatment, FMD did not significantly change in either the rofecoxib or placebo group (4.0 +/- 3.0% to 4.0 +/- 3.8% vs. 2.7 +/- 2.7% to 3.1 +/- 2.7%, respectively; p = 0.6 by two-way analysis of variance). Similarly, NMD remained unchanged in both groups. Levels of CRP, sICAM-1, and sIL-6r were not significantly altered in either the rofecoxib or placebo group.


CONCLUSIONS
The addition of selective COX-2 inhibition with rofecoxib did not appear to have any favorable or adverse effects on endothelial dysfunction or vascular inflammation in patients with CAD using concomitant low-dose aspirin.
Title
Lawrence M
LM
Division of Cardiology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada. ltitle@dal.ca
Giddens
Karen
K
McInerney
Michele M
MM
McQueen
Matthew J
MJ
Nassar
Bassam A
BA
D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D001916:Brachial Artery / Q000276:immunology / Q000503:physiopathology; D003324:Coronary Artery Disease / Q000097:blood / Q000276:immunology* / Q000503:physiopathology*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D013450:Sulfones; D016896:Treatment Outcome
D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D001241:Aspirin