on August 9, 2004
Published online before print August 9, 2004, doi: 10.1161/01.CIR.0000139338.12464.5F
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Submitted on December 10, 2003
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. * To whom correspondence should be addressed. E-mail: peter.Bogaty{at}med.ulaval.ca.
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 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.
Revised on April 29, 2004
Accepted on April 30, 2004
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
Peter Bogaty MD*,
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.
Key words: C-reactive protein • antiinflammatory agents, nonsteroidal • coronary disease • inflammation • interleukins
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