Cited by 168Inflammatory mediators and NSAID effectsAntiplatelet Therapy and Cardiovascular DiseasesEicosanoids and Hypertension Pharmacology

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COX-2 selectivity alone does not define the cardiovascular risks associated with non-steroidal anti-inflammatory drugs

Warner, Timothy D, Mitchell, Jane A·2008·The Lancet

DOI 10.1016/s0140-6736(08)60137-3

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CYCLOOXYGENASES 1 AND 2
Vane, J. R., Bakhle, Y. S., & Botting, R. M. (1998) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.38.1.97 · Cited by 2,763
Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: A full in vitro analysis
Warner, T. D., Giuliano, F., Vojnovic, I., Bukasa, A., Mitchell, J. A., & Vane, J. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7563 · Cited by 1,521
Self-citation
Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials
Kearney, P. M., Baigent, C., Godwin, J., Halls, H. J., Emberson, J., & Patrono, C. (2006) · BMJ · doi:10.1136/bmj.332.7553.1302 · Cited by 1,440
Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities
Großer, T. (2005) · Journal of Clinical Investigation · doi:10.1172/jci27291 · Cited by 1,031
Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress.
Topper, J., Cai, J., Falb, D., & Gimbrone, M. (1996) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.93.19.10417 · Cited by 922
Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study
Graham, D. J., Campen, D. H., Hui, R. L., Spence, M. M., Cheetham, C., Levy, G. D., Shoor, S., & Ray, W. A. (2005) · The Lancet · doi:10.1016/s0140-6736(05)17864-7 · Cited by 913
Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis
Henry, D. A., Lim, L. L.-Y., Rodriguez, L. A. G., Perez‐Gutthann, S., Carson, J. L., Griffin, M. R., Savage, R. L., Logan, R., Moride, Y., Hawkey, C. J., et al. (1996) · BMJ · doi:10.1136/bmj.312.7046.1563 · Cited by 827
Use of Nonsteroidal Antiinflammatory Drugs: An Update for Clinicians: A Scientific Statement From the American Heart Association
Antman, E. M., Bennett, J. S., Daugherty, A., Furberg, C., Roberts, H., & Taubert, K. A. (2007) · Circulation · doi:10.1161/circulationaha.106.181424 · Cited by 804
Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial
Farkouh, M. E., Kirshner, H. S., Harrington, R. A., Ruland, S. D., Verheugt, F. W. A., Schnitzer, T. J., Burmester, G. R., Mysler, E., Hochberg, M. C., Doherty, M., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16894-3 · Cited by 490
Effects of Nonsteroidal Antiinflammatory Drugs on Platelet Function and Systemic Hemostasis
Schafer, A. I. (1995) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1995.tb04050.x · Cited by 370

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Hermanson, D. J., Gamble‐George, J., Marnett, L. J., & Patel, S. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.04.006 · Cited by 121
“Cardiovascular side effects are exhibited by most NSAIDs, regardless of their selectivity for COX-2, due to a reduction in vascular PGI2 biosynthesis [114, 115].”
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“However, COX2 selectivity varies among c2s-NSAIDs, being greater for lumiracoxib, rofecoxib, etoricoxib, and valdecoxib and comparatively lower for celecoxib.(37) In addition, other potential mechanisms might influence the CV risk of an NSAID.”
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“Consequently, the anti-platelet effect of NSAIDs depends largely on dose and half-life of each individual compound [63].”
Background
NSAIDs-dependent adaption of the mitochondria-proteasome system in immortalized human cardiomyocytes
Brandolini, L., Antonosante, A., Giorgio, C., Bagnasco, M., d’Angelo, M., Castelli, V., Benedetti, E., Cimini, A., & Allegretti, M. (2020) · Scientific Reports · doi:10.1038/s41598-020-75394-x · Cited by 32
Naproxcinod, a new cyclooxygenase-inhibiting nitric oxide donator (CINOD)
Geusens, P. (2009) · Expert Opinion on Biological Therapy · doi:10.1517/14712590902926071 · Cited by 30
“Non-selective NSAIDs inhibit COX-1 and COX-2 and increase the relative risk of perforation, clinically manifest ulcer and bleeding (PUBs) and perforation, 1.”
BackgroundInfluential
Colonic anastomoses and non-steroidal anti-inflammatory drugs
Slim, K., Joris, J. L., & Beloeil, H. (2016) · Journal of Visceral Surgery · doi:10.1016/j.jviscsurg.2016.06.011 · Cited by 28
“[6] Warner TD, Mitchell JA.”
BackgroundInfluential
New Insights into Structural Determinants for Prostanoid Thromboxane A2 Receptor- and Prostacyclin Receptor-G Protein Coupling
Chakraborty, R., Pydi, S. P., Gleim, S., Bhullar, R. P., Hwa, J., Dakshinamurti, S., & Chelikani, P. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00725-12 · Cited by 30
“, ibuprofen) (6, 7) highlight the importance of understanding the G protein specificity of these opposing receptors.”
Background
Can drug removals involving cyclooxygenase-2 inhibitors be avoided? A plea for human pharmacology
Hinz, B., & Brune, K. (2008) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.06.004 · Cited by 26
The Global Burden of Resistant Hypertension and Potential Treatment Options
Buso, G., Rosei, C. A., Lemoli, M., Corvini, F., & Muiesan, M. L. (2024) · European Cardiology Review · doi:10.15420/ecr.2023.51 · Cited by 30
Pharmacological Management of Acute Endodontic Pain
khan, A. W. A., & Diogenes, A. R. (2021) · Drugs · doi:10.1007/s40265-021-01564-4 · Cited by 27
Evaluation of NT-proBNP and High Sensitivity C-Reactive Protein for Predicting Cardiovascular Risk in Patients with Arthritis Taking Longterm Nonsteroidal Antiinflammatory Drugs
Ruff, C. T., Morrow, D. A., Jarolim, P., REN, F., Contant, C. F., Kaur, A., Curtis, S., Laine, L., Cannon, C. P., & Brune, K. (2011) · The Journal of Rheumatology · doi:10.3899/jrheum.100880 · Cited by 23
Balancing Risks and Benefits of Cyclooxygenase-2 Selective Nonsteroidal Anti-Inflammatory Drugs
Scheiman, J. M. (2009) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2009.03.006 · Cited by 22
“Although there are theoretical reasons why COX-2 selective agents may be prothrombotic, such as decreased production of the vasodilator prostacyclin (which also inhibits platelet activation)with concomitantunimpeded COX-1–mediated production of platelet thromboxane A2, the mechanistic relationship to CV events remains…”
Background
Relative Cardiovascular and Gastrointestinal Safety of Non-selective Non-steroidal Anti-inflammatory Drugs Versus Cyclo-oxygenase-2 Inhibitors
Patrício, J. P. H., Barbosa, J., Ramos, R. M. M., Antunes, N. F. P., & de Melo, P. C. S. (2013) · Clinical Drug Investigation · doi:10.1007/s40261-013-0052-6 · Cited by 23
Hypertension Update and Cardiovascular Risk Reduction in Physically Active Individuals and Athletes
Oliveira, L., & Lawless, C. E. (2010) · The Physician and Sportsmedicine · doi:10.3810/psm.2010.04.1757 · Cited by 21
Room for improvement: unmet needs in postoperative pain management
Pogatzki-Zahn, E. M., Schnabel, A., & Zahn, P. K. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.12.30 · Cited by 20
Resistant hypertension: A stepwise approach
Yahr, J., Thomas, G., Calle, J., & Taliercio, J. J. (2023) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.90a.22046 · Cited by 23
Human whole blood assay for rapid and routine testing of non-steroidal anti-inflammatory drugs (NSAIDs) on cyclo-oxygenase-2 activity
Laufer, S., Greim, C., Luik, S., Ayoub, S. S., & Dehner, F. (2008) · Inflammopharmacology · doi:10.1007/s10787-008-8007-x · Cited by 20
Evidence that diclofenac and celecoxib are thyroid hormone receptor beta antagonists
Zloh, M., Diaz, N. P., Tang, L., Patel, P., & Mackenzie, L. S. (2016) · Life Sciences · doi:10.1016/j.lfs.2016.01.013 · Cited by 20
“Clinical trials revealed the side effects of both pan- and COX-1 sparing NSAIDs led to gastrointestinal damage and cardiovascular complications including myocardial infarction [2,3].”
Background
Cardiovascular risk associated with nonsteroidal anti-inflammatory drugs
Hermann, M. (2009) · Current Rheumatology Reports · doi:10.1007/s11926-009-0005-5 · Cited by 19
Nitric Oxide Release Is Not Required to Decrease the Ulcerogenic Profile of Nonsteroidal Anti-inflammatory Drugs
Jain, S., Tran, S., Gendy, M. A. M. E., Kashfi, K., Jurasz, P., & Velázquez‐Martínez, C. A. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200973j · Cited by 19
Rates of Nonsteroidal Anti-Inflammatory Drug Use in Patients with Established Cardiovascular Disease: A Retrospective, Cross-Sectional Study from NHANES 2009–2010
Castelli, G., Petrone, A. B., Xiang, J., Shrader, C. D., & King, D. E. (2017) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-016-0212-1 · Cited by 18
“One potential mechanism might be NSAID-induced increased blood pressure in both normotensive and hypertensive patients [16, 17].”
Background
Was the thrombotic risk of rofecoxib predictible from the French Pharmacovigilance Database before 30 September 2004?
Sommet, A., Grolleau, S., Bagheri, H., Lapeyre‐Mestre, M., & Montastruc, J. (2008) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-008-0497-3 · Cited by 18
“Recently, Warmer and Mitchell [ 33 ] suggested that the COX-2 selectivity alone could not explain the cardiovascular risk.”
Background
Nonsteroidal Anti-Inflammatory Drugs and Their Effects in the Elderly
Park, K. E., Qin, Y., & Bavry, A. A. (2012) · Aging Health · doi:10.2217/ahe.12.6 · Cited by 17
Nonsteroidal Anti-Inflammatory Drugs and Cardiovascular Risk
Minuz, P. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.08.042 · Cited by 17
“This finding suggests that the degree of COX inhibition by therapeutic levels of NSAIDs should be considered the major determinant of cardiovascular risk (6,12, 14 ).”
Konzepte zur perioperativen Schmerztherapie
Reichl, S., & Pogatzki-Zahn, E. M. (2009) · Der Anaesthesist · doi:10.1007/s00101-009-1589-x · Cited by 15
Risk Factors for Asymptomatic Echocardiographic Abnormalities that Predict Symptomatic Heart Failure
Coller, J. M., Gong, F. F., McGrady, M., Shiel, L. M., Liew, D., Stewart, S., Owen, A. J., Krum, H., Reid, C. M., Prior, D., et al. (2021) · ESC Heart Failure · doi:10.1002/ehf2.13695 · Cited by 15
“the increased CVD risk and doubling of HF risk by NSAID therapy.(42,43) NSAID therapy increases BP(44); however, the specific association of NSAID therapy with structural abnormality”
Background
Pharmacological assessment of ibuprofen arginate on platelet aggregation and colon cancer cell killing
Ahmetaj‐Shala, B., Tesfai, A., Constantinou, C., Leszczynski, R., Chan, M. V., Gashaw, H. H., Galaris, G., Mazi, S. I., Warner, T., Kirkby, N. S., et al. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.01.161 · Cited by 15
Self-citation
Current considerations for the management of musculoskeletal pain in A sian countries: a special focus on cyclooxygenase‐2 inhibitors and non‐steroid anti‐inflammation drugs
Chaudakshetrin, P., Penserga, E. G., Lee, D. J., Chen, S., Gill, R. S., Hamid, A., Kumthornthip, W., Liu, Y., Meliala, L., Misbach, H. J., et al. (2012) · International Journal of Rheumatic Diseases · doi:10.1111/j.1756-185x.2012.01769.x · Cited by 14
Increased Risk for Complications After Colorectal Surgery With Selective Cyclo-oxygenase 2 Inhibitor Etoricoxib
Zittel, T., Razavi, D., Papp, A., & Lundberg, K. (2013) · Diseases of the Colon & Rectum · doi:10.1097/dcr.0b013e318285bb5a · Cited by 13
“06 CRP, mg/L Preop 12 (6; 18) 11 (7; 15) 0.”
Ibuprofen arginate retains eNOS substrate activity and reverses endothelial dysfunction: implications for the COX‐2/ADMA axis
Kirkby, N. S., Tesfai, A., Ahmetaj‐Shala, B., Gashaw, H. H., Sampaio, W. O., Etelvino, G. M., Leão, N. M., Santos, R. A. S., & Mitchell, J. A. (2016) · The FASEB Journal · doi:10.1096/fj.201600647r · Cited by 14
Self-citation
The Use of NSAIDs in the Postoperative Period: Advantage and Disadvantages
(2015) · Journal of Anesthesia & Critical Care Open Access · doi:10.15406/jaccoa.2015.03.00107 · Cited by 14
In vitro pharmacological evaluation of multitarget agents for thromboxane prostanoid receptor antagonism and COX-2 inhibition
Hoxha, M., Buccellati, C., Capra, V., Garella, D., Cena, C., Rolando, B., Fruttero, R., Carnevali, S., Sala, A., Rovati, G. E., et al. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.11.012 · Cited by 14
Analgesic targets: today and tomorrow
Rodger, I. (2009) · InflammoPharmacology · doi:10.1007/s10787-009-0006-z · Cited by 12
Immunomodulatory Potential of Diuretics
Bryniarski, P., Nazimek, K., & Marcinkiewicz, J. (2021) · Biology · doi:10.3390/biology10121315 · Cited by 12
Nonopioid Analgesics
Williams, B. S. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-40196-8.00051-6 · Cited by 12
Piroxicam and meloxicam ameliorate hepatic oxidative stress and protein carbonylation in Kupffer and sinusoidal endothelial cells promoted by ischemia-reperfusion injury
Montalvo-Jave, E. E., Ortega-Salgado, J. A., Castell, A., Carrasco‐Daza, D., Jay, D., Gleason, R., Muñóz, E., Montalvo-Arenas, C., Hernández-Muñoz, R. E., & Piña, E. (2011) · Transplant International · doi:10.1111/j.1432-2277.2010.01214.x · Cited by 10
Nonsteroidal Anti-Inflammatory Drugs: Exploiting Bivalent COXIB/ TP Antagonists for the Control of Cardiovascular Risk
Carnevali, S., Buccellati, C., Bolego, C., Bertinaria, M., Rovati, G. E., & Sala, A. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666170602083428 · Cited by 10
“Indeed, retrospective analysis showed that CV risk is linked not only to COXIBs but also to first generation antiinflammatory tNSAIDS [44, 77-82], and, in addition, tNSAIDs have also been observed to interfere with the cardio-protective effect of low-dose aspirin, somehow jeopardizing the benefit of their association…”
Background
Naproxen Twice Daily Versus as Needed (PRN) Dosing: Efficacy and Tolerability for Treatment of Acute Ankle Sprain, a Randomized Clinical Trial
Hajimaghsoudi, M., Jalili, M., Mokhtari, M., Nejati, A., Mesbahi, J., & Paydary, K. (2013) · Asian Journal of Sports Medicine · doi:10.5812/asjsm.11411 · Cited by 9
“They concluded that “Use of low risk drugs in low dosage as first line treatment would substantially reduce the morbidity and mortality due to serious gastrointestinal toxicity from these drugs”([19]).”
Background
Effects of cox inhibitors on bone and tendon healing
Dimmen, S. (2011) · Acta Orthopaedica · doi:10.3109/17453674.2011.555370 · Cited by 9
Factors Affecting Quality of Life and Satisfaction in Patients with Arthritis after Change to a Fixed-Dose Naproxen/Esomeprazole Combination Drug
Park, D.-H., & Kwon, Y.-U. (2020) · Clinics in Orthopedic Surgery · doi:10.4055/cios.2020.12.1.86 · Cited by 9
Neue Substanzen und Applikationsformen für die postoperative Schmerztherapie
Pogatzki-Zahn, E. M., & Zahn, P. K. (2008) · Der Schmerz · doi:10.1007/s00482-008-0665-5 · Cited by 9
Potential role of NSAIDs loaded nano-formulations to treat inflammatory diseases
Zahoor, I., Bala, R., Wani, S. N., Chauhan, S., Madaan, R., Kumar, R., Hakeem, K. R., & Malik, I. A. (2025) · Inflammopharmacology · doi:10.1007/s10787-025-01644-x · Cited by 8
“Consequently, the encapsulation of NSAIDs does not alter their COX-1/COX-2 selectivity however, it modifies the in vivo biodistribution of the encapsulated drug, preventing its accumulation in tissues susceptible to NSAID-related adverse effects (Warner and Mitchell 2008).”

Authors: Warner, T. D., & Mitchell, J. A.
Affiliations: Queen Mary University of London (GB)
Royal Brompton Hospital (GB)
Corresponding author: Warner, Timothy D
ORCID: Warner, Timothy D
Mitchell, Jane A
Venue: The Lancet
Publisher: Elsevier BV
Published: 2008-01
Volume: 371
Issue: 9608
Pages: 270-273
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(08)60137-3
OpenAlex: W2164162242
Cited by: 166
References: 22
Citations by year: 2026: 1 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 4 · 2018: 10 · 2017: 8 · 2016: 8 · 2015: 7 · 2014: 12 · 2013: 9 · 2012: 16
FWCI: 13.60
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Topics: Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords: COX-2 selectivity, nonsteroidal anti-inflammatory drugs, cardiovascular risk, thrombosis risk, gastrointestinal risk, cyclooxygenase inhibition, cyclooxygenase-1, cyclooxygenase-2, etoricoxib, rofecoxib, celecoxib, lumiracoxib, drug safety, cardiovascular adverse events, gastrointestinal adverse effects, American Heart Association guidelines
MeSH terms: Anti-Inflammatory Agents, Non-Steroidal, Dose-Response Relationship, Drug, Gastrointestinal Diseases, Humans, Myocardial Infarction, Risk Factors, Thrombosis, Cyclooxygenase 2 Inhibitors

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COX-2 selectivity alone does not define the cardiovascular risks associated with non-steroidal anti-inflammatory drugs

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