Circulation. 2003;107:405-409
Published online before print January 13, 2003, doi: 10.1161/01.CIR.0000051361.69808.3A
Published online before print January 13, 2003, doi: 10.1161/01.CIR.0000051361.69808.3A
(Circulation. 2003;107:405.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Selective COX-2 Inhibition Improves Endothelial Function in Coronary Artery Disease
From the Cardiovascular Center, Cardiology and Department of Rheumatology (S.G., R.G., M.N., B.M.), University Hospital Zürich, and Institute for Clinical Chemistry, Kantonsspital St Gallen (W.R.), Switzerland.
Correspondence to Frank Ruschitzka, MD, FESC, Cardiology, University Hospital, Rämistrasse 100, CH-8091 Zürich, Switzerland. E-mail frank.ruschitzka{at}dim.usz.ch
Background— There is an ongoing debate as to whether the gastrointestinal safety of COX-2 inhibition compared with nonsteroidal antiinflammatory drugs (NSAIDs) may come at the cost of increased cardiovascular events. In view of the large number of patients at cardiovascular risk requiring chronic analgesic therapy with COX-2 inhibitors for arthritic and other inflammatory conditions, the effects of selective COX-2 inhibition on clinically useful surrogates for cardiovascular disease, particularly endothelial function, need to be determined.
Methods and Results— Fourteen male patients (mean age, 66±3 years) with severe coronary artery disease (average of 2.6 vessels with stenosis >75%) undergoing stable background therapy with aspirin and statins were included. The patients received celecoxib (200 mg BID) or placebo for a duration of 2 weeks in a double-blind, placebo-controlled, crossover fashion. After each treatment period, flow-mediated dilation of the brachial artery, high-sensitivity C-reactive protein, oxidized LDL, and prostaglandins were measured. Celecoxib significantly improved endothelium-dependent vasodilation compared with placebo (3.3±0.4% versus 2.0±0.5%, P=0.026), whereas endothelium-independent vasodilation, as assessed by nitroglycerin, remained unchanged (9.0±1.6% versus 9.5±1.3%, P=0.75). High-sensitivity C-reactive protein was significantly lower after celecoxib (1.3±0.4 mg/L) than after placebo (1.8±0.5 mg/L, P=0.019), as was oxidized LDL (43.6±2.4 versus 47.6±2.6 U/L, P=0.028), whereas prostaglandins did not change.
Conclusions— This is the first study to demonstrate that selective COX-2 inhibition improves endothelium-dependent vasodilation and reduces low-grade chronic inflammation and oxidative stress in coronary artery disease. Thus, selective COX-2 inhibition holds the potential to beneficially impact outcome in patients with cardiovascular disease.
Key Words: coronary disease • arteriosclerosis • endothelium • inflammation • free radicals
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