Published online before print August 9, 2004, doi: 10.1161/01.CIR.0000139338.12464.5F
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(Circulation. 2004;110:934-939.)
© 2004 American Heart Association, Inc.
Original Articles |
Impact of Prolonged Cyclooxygenase-2 Inhibition on Inflammatory Markers and Endothelial Function in Patients With Ischemic Heart Disease and Raised C-Reactive Protein
A Randomized Placebo-Controlled Study
From the Quebec Heart Institute/Laval Hospital, Laval University, Quebec City (P.B., M.N., L.B., S.S., F.B., G.R.D.), and McGill University Health Center, McGill University, Montreal (J.M.B.), Quebec, Canada.
Correspondence to Peter Bogaty, MD, Quebec Heart Institute/Laval Hospital, 2725 Chemin Ste-Foy, Quebec, Canada G1V 4G5. E-mail peter.Bogaty{at}med.ulaval.ca
Received December 10, 2003; de novo received March 5, 2004; revision received April 29, 2004; accepted April 30, 2004.
Background— The impact of cyclooxygenase (COX)-2 antagonist treatment on acute coronary risk is controversial. We investigated the effect of prolonged COX-2 inhibition on inflammatory profile and endothelial function in patients with ischemic heart disease and high serum C-reactive protein (CRP) values.
Methods and Results— In a double-blind study, 35 stable subjects on low-dose aspirin with 
2 previous acute coronary events and 2 of 2 screening CRP values >2.0 mg/L were randomized to the COX-2 inhibitor rofecoxib (25 mg) or placebo daily for 6 months. Serum CRP, interleukin-6 (IL-6), P-selectin, matrix metalloproteinase-9 (MMP-9), and brachial artery endothelial function were evaluated. In the placebo group, CRP (median) was 3.16 mg/L (25% and 75% quartiles, 1.90 and 5.78 mg/L) at baseline and 4.22 mg/L (25% and 75% quartiles, 2.04 and 6.25 mg/L) at 6 months; in the rofecoxib group, CRP was 3.45 mg/L (25% and 75% quartiles, 2.08 and 5.78 mg/L) at baseline and 1.41 mg/L (25% and 75% quartiles, 1.17 and 4.81 mg/L) at 6 months (P=0.03). Rofecoxib compared with placebo also lowered IL-6 at 6 months (P=0.0002). There was a significant off-drug effect on CRP and IL-6 levels in the rofecoxib group 3 months after treatment (P=0.005 and P=0.009, respectively). Rofecoxib did not significantly affect P-selectin, MMP-9, and brachial artery vasoreactivity.
Conclusions— Prolonged COX-2 inhibition attenuates CRP and IL-6, does not modify P-selectin and MMP-9, and has no deleterious effect on endothelial function in stable patients with a history of recurrent acute coronary events and raised CRP. These results strengthen the rationale for evaluating the clinical benefit of COX-2 inhibition in patients with ischemic heart disease.
Key Words: C-reactive protein • antiinflammatory agents, nonsteroidal • coronary disease • inflammation • interleukins
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