CLINICAL RESEARCH: VASCULAR EFFECTS OF ROFECOXIB AND ROSIGLITAZONE
Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction and inflammatory markers in patients with coronary artery disease
Lawrence M. Title, MD*,*,
Karen Giddens, RDCS*,
Michele M. McInerney, RN*,
Matthew J. McQueen, MBChB, PhD and
Bassam A. Nassar, MB, BCh, PhD
* Division of Cardiology, Halifax, Nova Scotia, Canada
Department of Pathology and Laboratory Medicine at the Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
* Reprint requests and correspondence: Dr. Lawrence M. Title, Queen Elizabeth II Health Sciences Centre, Division of Cardiology, 6896-1796 Summer Street, Halifax, Nova Scotia, Canada B3H 3A7.
ltitle{at}dal.ca
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | ANOVA | = analysis of variance | | CAD | = coronary artery disease | | COX-2 | = cyclooxygenase-2 | | CRP | = C-reactive protein | | FMD | = flow-mediated dilation | | NMD | = nitroglycerin-mediated dilation | | NSAID | = nonsteroidal anti-inflammatory drug | | sICAM-1 | = soluble intercellular adhesion molecule-1 | | sIL-6r | = soluble interleukin-6 receptor | | VIGOR | = VIoxx Gastrointestinal Outcomes Research |
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