Abstract
Since the discovery of COX-2, a second subtype of cyclooxygenase, selective inhibitors or "coxibs" were developed with the idea that this isoform was inducible at the site of inflammation whereas COX-1 was expressed constitutively in several tissues including gastric epithelium. This new class of non steroidal anti-inflammatory agents was though to be safer for ulcerations of the gastroinstestinal mucosa observed with non selective COX-2 inhibitors. Nevertheless, at the end of September 2004, Merck & Co announced the voluntary withdrawal of rofecoxib (Vioxx) worldwide because of an increased risk of cardiovascular events. This decision raised serious concerns about safety of selective COX-2 inhibitors which are actively marketed today, and the ones currently under development. The mechanism of this cardiovascular toxicity could lie in the inhibition of COX-2 itself, and thus be a class effect. On the other hand, these cardiovascular side effects could be limited on rofecoxib and be dependent on its chemical and/or pharmacological own properties. This hypothesis is undermined by the unexpected findings of one colon cancer study which has shown that celecoxib might also increase the chance of heart attack and stroke in some patients. In this review, we compared the different coxibs marketed to date on the basis of their clinical, pharmacological and chemical properties with the aim of providing some clues in the understanding of their potential or revealed "cardiovascular effects".
Keywords: NSAIDs, prostacyclin, COX-2 inhibitors, thrombosis, valdecoxib
Current Pharmaceutical Design
Title: Coxibs and Cardiovascular Side-Effects: From Light to Shadow
Volume: 12 Issue: 8
Author(s): Jean-Michel Dogne, Julien Hanson, Claudiu Supuran and Domenico Pratico
Affiliation:
Keywords: NSAIDs, prostacyclin, COX-2 inhibitors, thrombosis, valdecoxib
Abstract: Since the discovery of COX-2, a second subtype of cyclooxygenase, selective inhibitors or "coxibs" were developed with the idea that this isoform was inducible at the site of inflammation whereas COX-1 was expressed constitutively in several tissues including gastric epithelium. This new class of non steroidal anti-inflammatory agents was though to be safer for ulcerations of the gastroinstestinal mucosa observed with non selective COX-2 inhibitors. Nevertheless, at the end of September 2004, Merck & Co announced the voluntary withdrawal of rofecoxib (Vioxx) worldwide because of an increased risk of cardiovascular events. This decision raised serious concerns about safety of selective COX-2 inhibitors which are actively marketed today, and the ones currently under development. The mechanism of this cardiovascular toxicity could lie in the inhibition of COX-2 itself, and thus be a class effect. On the other hand, these cardiovascular side effects could be limited on rofecoxib and be dependent on its chemical and/or pharmacological own properties. This hypothesis is undermined by the unexpected findings of one colon cancer study which has shown that celecoxib might also increase the chance of heart attack and stroke in some patients. In this review, we compared the different coxibs marketed to date on the basis of their clinical, pharmacological and chemical properties with the aim of providing some clues in the understanding of their potential or revealed "cardiovascular effects".
Export Options
About this article
Cite this article as:
Dogne Jean-Michel, Hanson Julien, Supuran Claudiu and Pratico Domenico, Coxibs and Cardiovascular Side-Effects: From Light to Shadow, Current Pharmaceutical Design 2006; 12 (8) . https://dx.doi.org/10.2174/138161206776055949
DOI https://dx.doi.org/10.2174/138161206776055949 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Therapeutic Application of Melatonin in the Treatment of Melanoma: A Review
Current Cancer Therapy Reviews Overexpression of Bromodomain and Extraterminal Domain is Associated with Progression, Metastasis and Unfavorable Outcomes: Highlighting Prognostic and Therapeutic Value of the BET Protein Family in Gastric Cancer
Anti-Cancer Agents in Medicinal Chemistry Recent Patents on Oral Combination Drug Delivery and Formulations
Recent Patents on Drug Delivery & Formulation Hsa_Circ_0000021 Sponges miR-3940-3p/KPNA2 Expression to Promote Cervical Cancer Progression
Current Molecular Pharmacology Cytotoxic Nucleoside Analogues: Different Strategies to Improve their Clinical Efficacy
Current Medicinal Chemistry Editorial [Hot Topic: Targeted Cancer Therapies: Current Status and Future Directions (Guest Editors: Ioannis Starakis)]
Current Medicinal Chemistry Ion-Responsive Drug Delivery Systems
Current Drug Targets The Chemoprotective Potentials of Alpha-lipoic Acid against Cisplatin-induced Ototoxicity: A Systematic Review
Current Medicinal Chemistry MicroRNA and Bone Tumor: To Up Date
Current Signal Transduction Therapy Immunotoxins Constructed with Ribosome-Inactivating Proteins and their Enhancers: A Lethal Cocktail with Tumor Specific Efficacy
Current Pharmaceutical Design The Antitumor Effects of Icaritin Against Breast Cancer is Related to Estrogen Receptors
Current Molecular Medicine The Applications of Next-generation Sequencing (NGS) in Drug Development for Cancer Therapy
Current Analytical Chemistry The Possible Existence of a Gut-Bone Axis Suggested by Studies of Genetically Manipulated Mouse Models?
Current Pharmaceutical Design Functional Nanoplatforms for Enhancement of Chemotherapeutic Index
Anti-Cancer Agents in Medicinal Chemistry MicroRNA-Mediated Cancer Metastasis Regulation via Heterotypic Signals in the Microenvironment
Current Pharmaceutical Biotechnology Contrast Enhanced Ultrasonography for Focal Liver Lesions Characterization: Clinical Perspective
Current Medical Imaging Counter-Regulatory Role of Bile Acid Activated Receptors in Immunity and Inflammation
Current Molecular Medicine Evolutioninthe Pharmacogenetics and Pharmacogenomics of Inflammatory Bowel Disease - Order Slowly Rises from the Chaos
Current Pharmacogenomics Mucoadhesive Nanoparticulate System for Oral Drug Delivery: A Review
Current Drug Therapy Gold Complexes for Therapeutic Purposes: an Updated Patent Review (2010-2015)
Current Medicinal Chemistry