Chest
Clinical InvestigationsCARDIOLOGYRofecoxib, a COX-2 Inhibitor, Lowers C-Reactive Protein and Interleukin-6 Levels in Patients With Acute Coronary Syndromes
Section snippets
Materials and Methods
This was a prospective, randomized, double-blind, placebo-controlled study. Patients hospitalized for non–ST-segment elevation ACS were randomized to receive either rofecoxib, 25 mg/d, plus 100 mg of aspirin, or placebo plus 100 mg of aspirin for a period of 3 months. Regarding the randomization of the patients, a tablet of rofecoxib, 25 mg, or a placebo tablet was put into a nontransparent capsule. The hospital pharmacist distributed the medications in separate dark boxes. The boxes were
Results
Thirty-four patients participated in the study, and all completed at least 1 month of treatment; 18 patients received rofecoxib, and 16 patients received placebo. Of the 23 patients who completed 3 months of treatment, 12 patients received rofecoxib and 11 patients received placebo. Most of the patients who did not complete the 3-month follow-up were excluded, mainly due to the development of infections and inflammatory conditions that could potentially elevate the inflammatory markers studied.
Discussion
The main findings of this study were that treatment with rofecoxib, a COX-2 inhibitor, in patients hospitalized for ACS was associated with significant reduction of CRP and IL-6 levels. The reduction in both CRP and IL-6 levels was observed after 1 month of treatment and persisted for 3 months. The treatment was well tolerated. The reduction in CRP and IL-6 was observed in patients already receiving medical treatment, as all patients were treated with aspirin and most were receiving HMG-CoA
References (50)
- et al.
Elevation of C- reactive protein in “active” coronary artery disease
Am J Cardiol
(1990) - et al.
Predictive value of C-reactive protein and troponin T in patients with unstable angina: a comparative analysis
J Am Coll Cardiol
(2000) - et al.
Experimental endotoxemia in humans: analysis of cytoline release and coagulation, fibrinolytic and complement pathways
Blood
(1990) - et al.
Differential induction of the interleukin-6 gene by tumor necrosis factor and interleukin-1
J Biol Chem
(1994) - et al.
Triggering of the human interleukin-6 gene by interferon-γ and tumor necrosis factor-α in monocyte cells involves cooperation between interferon regulatory factor-1, NFκB and SP1 transcription factors
J Biol Chem
(1995) - et al.
Interleukin-6 gene transcripts are expressed in human atherosclerotic lesion
Cytokine
(1994) - et al.
Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall
Atherosclerosis
(1996) - et al.
Elevated plasma interleukin-6 levels in patients with acute myocardial infarction
Am Heart J
(1993) - et al.
The effect of aspirin on C-reactive protein as a marker of risk in unstable angina
J Am Coll Cardiol
(2001) - et al.
Evaluation of serum levels of solubilized adhesion molecules receptors in coronary heart disease
J Am Coll Cardiol
(1999)
Expression of cyclo-oxygenase-2 in human atherosclerotic carotid arteries
Eur J Vasc Endovasc Surg
Inhibition of cyclooxygenase-2 improves cardiac function in myocardial infarction
Biochem Biophys Res Commun
COX-2 selective non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease
Lancet
A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthriris
Gastroenterology
Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis
Lancet
Inflammatory markers in men with angiographically documented coronary heart disease
Clin Chem
Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin
Circulation
Elevated levels of interleukin-6 in unstable angina
Circulation
The prognostic value of C-reactive protein and serum amyloid A in severe unstable angina
N Engl J Med
Production of C-reactive protein and risk of coronary events in stable and unstable angina
Lancet
Inflammatory status as a main determinant of outcome in patients with unstable angina, independent of coagulation activation, and endothelial cell function
Eur Heart J
Increasing levels of interleukin (IL)1Ra and IL-6 during the first 2 days of hospitalization in unstable angina are associated with increased risk of in-hospital coronary events
Circulation
Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study
Am J Epidemiol
Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men
N Engl J Med
C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men
Circulation
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2021, Heart Lung and CirculationCitation Excerpt :Non-steroidal anti-inflammatory medications are associated with an increased risk of adverse cardiovascular events irrespective of whether they are non-selective cyclooxygenase (COX) or COX-2 selective inhibitors [59]. Randomised controlled trials showed that COX-2 inhibitors reduce HsCRP levels in patients after an acute coronary syndrome [60,61]. However, in the Vioxx Gastrointestinal Outcomes Research (VIGOR) study patients treated with Rofecoxib (a COX-2 inhibitor) had more myocardial infarctions than patients treated with naproxen (COX-1 inhibitor) [62].
Vascular effects of glycoprotein130 ligands - Part II: Biomarkers and therapeutic targets
2012, Vascular PharmacologyCitation Excerpt :Treatment with aspirin reduced plasma levels of IL-6 in patients with stable CAD (Ikonomidis et al., 1999) and acute MI (Solheim et al., 2003). Patients recovering from ACS had lower levels of IL-6 at one month when treated with rofecoxib, a COX-2 inhibitor, plus aspirin (Monakier et al., 2004). However, the level of sIL-6R did not significantly change in the rofecoxib group in patients with CAD (Title et al., 2003).
Beyond thrombosis: The versatile platelet in critical illness
2011, ChestCitation Excerpt :In patients with chronic, stable angina, for instance, aspirin significantly lowered CRP and inflammatory cytokine levels.59 Conversely, in other patients with chronic ischemic heart disease, recent myocardial infarction, and acute coronary syndromes, aspirin failed to reliably reduce CRP.60,61 In peripheral arterial disease as well, markers of platelet-mediated inflammation were not significantly decreased with aspirin therapy.62
Cyclooxygenase products and atherosclerosis
2008, Drug Discovery Today: Therapeutic StrategiesCitation Excerpt :If COX-2 plays a critical role in mediating PGI2 production by arterial endothelial cells in vivo, one would anticipate that treatment with COX-2 inhibitors might result in impaired endothelium-dependent vasodilation. By contrast, five studies in humans have found no impact of COX-2 inhibition on endothelium-dependent vasodilation [47–51], whereas two studies actually found that treatment with COX-2 inhibitors improved endothelium-dependent vasodilation [52,53]. In summary, the studies investigating COX-2 inhibition and endothelial function in humans in vivo have found either no impact or a beneficial effect.
Divergent effects of rofecoxib on endothelial function and inflammation in acute coronary syndromes
2006, International Journal of Cardiology