Cox-2: where are we in 2003? - Cardiovascular risk and Cox-2 inhibitors.
TLDR
The widespread use of these agents mandates prospective, randomized evaluation of the cardiovascular safety of COX-2 inhibitors, and available clinical data and basic biological studies raise significant concern about the potential prothrombotic effect of this class of drugs.Abstract:
Selective cyclooxygenase-2 (COX-2) inhibitors were developed to reduce the gastrointestinal toxicity of conventional nonsteroidal anti-inflammatory agents. However, COX-2 inhibitors decrease prostacyclin production and may disrupt the normal homeostatic balance, leading to a prothrombotic state and offsetting the potential gastrointestinal benefits. Available clinical data and basic biological studies raise significant concern about the potential prothrombotic effect of this class of drugs. Two recent studies with a newer, more selective COX-2 inhibitor have added to the already existing concern about the cardiovascular safety of these agents. The widespread use of these agents mandates prospective, randomized evaluation of the cardiovascular safety of COX-2 inhibitors.read more
Citations
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COX-2: A Molecular Target for Colorectal Cancer Prevention
Joanne Brown,Raymond N. DuBois +1 more
TL;DR: Observational and randomized controlled studies have demonstrated protective effects of nonsteroidal anti-inflammatory drugs (NSAIDs; the inhibitors of COX activity) for colorectal cancers (CRCs), and COX-2, the inducible isoform of cyclooxygenase, is overexpressed in early and advanced CRC tissues, which portends a poor prognosis.
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Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison
Christopher P. Cannon,Sean P. Curtis,Garret A. FitzGerald,Henry Krum,Amarjot Kaur,James A. Bolognese,Alise S. Reicin,Claire Bombardier,Michael E. Weinblatt,Désirée van der Heijde,Erland Erdmann,Loren Laine +11 more
TL;DR: Rates of thrombotic cardiovascular events in patients with arthritis on etoricoxib are similar to those in patients on diclofenac with long-term use of these drugs.
Journal ArticleDOI
Up-regulation of microsomal prostaglandin E synthase 1 in osteoarthritic human cartilage: critical roles of the ERK-1/2 and p38 signaling pathways.
Kayo Masuko-Hongo,Francis Berenbaum,Lydie Humbert,Colette Salvat,Mary B. Goldring,Sylvie Thirion +5 more
TL;DR: This study is the first to show that mPGES-1 is stimulated in human chondrocytes by the proinflammatory cytokine IL-1beta via activation of both ERK-1/2 and p38 MAPK in an isoform-specific manner.
Journal ArticleDOI
Preventing the Development of Chronic Pain After Orthopaedic Surgery with Preventive Multimodal Analgesic Techniques
TL;DR: Effective multimodal analgesic techniques include the use of nonsteroidal anti-inflammatory drugs, local anesthetics, alpha-2 agonists, ketamine, alpha(2)-delta ligands, and opioids.
Journal ArticleDOI
High sensitivity C-reactive protein in systemic lupus erythematosus: relation to disease activity, clinical presentation and implications for cardiovascular risk
Elena V. Barnes,Sonali Narain,Arlene Naranjo,Jonathan J. Shuster,Mark S. Segal,Eric S. Sobel,A E Armstrong,B E Santiago,Westley H. Reeves,Hanno B. Richards +9 more
TL;DR: Measurement of hs-CRP, though not valuable as marker of disease activity in SLE may be of some use in the assessment of cardiovascular risk, and it is speculated that antimalarials may help to reduce cardiovascular risk in patients with SLE.
References
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Journal ArticleDOI
Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis
Claire Bombardier,Loren Laine,Alise S. Reicin,Deborah R. Shapiro,Ruben Burgos-Vargas,Barry R. Davis,Richard O. Day,Marcos Bosi Ferraz,Christopher J. Hawkey,Marc C. Hochberg,Tore K Kvien,Thomas J. Schnitzer +11 more
TL;DR: In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.
Journal ArticleDOI
Gastrointestinal Toxicity With Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis: The CLASS Study: A Randomized Controlled Trial
Fred E. Silverstein,Gerald A. Faich,Jay L. Goldstein,Lee S. Simon,Theodore Pincus,Andrew Whelton,Robert W. Makuch,Glenn M. Eisen,Naurang M. Agrawal,William F. Stenson,Aimee M. Burr,William W. Zhao,Jeffrey D. Kent,James B. Lefkowith,Kenneth M. Verburg,G. Steven Geis +15 more
TL;DR: In this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages.
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TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue
TL;DR: The expression of the TIS10 gene appears to be highly cell type-restricted in cultured cell lines; of 12 cell lines tested under superinducing conditions, only the rodent embryonic Swiss 3T3 and Rat1 cell lines expressed TIS12 gene.
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Risk of cardiovascular events associated with selective COX-2 inhibitors.
TL;DR: The results from VIGOR showed that the relative risk of developing a confirmed adjudicated thrombotic cardiovascular event with rofecoxib treatment compared with naproxen was higher than that in the placebo group of a recent meta-analysis of 23 407 patients in primary prevention trials.
Journal ArticleDOI
Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2.
B. F. McAdam,Francesca Catella-Lawson,I. A. Mardini,Shiv Kapoor,John A. Lawson,Garret A. FitzGerald +5 more
TL;DR: In this paper, the effects of celecoxib on indices of COX-1-dependent platelet thromboxane (Tx) A2 and on systemic biosynthesis of prostacyclin in vivo were examined.