Biomaterial Database

Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial. 2004

Michael E Farkouh, and Howard Kirshner, and Robert A Harrington, and Sean Ruland, and Freek W A Verheugt, and Thomas J Schnitzer, and Gerd R Burmester, and Eduardo Mysler, and Marc C Hochberg, and Michael Doherty, and Elena Ehrsam, and Xavier Gitton, and Gerhard Krammer, and Bernhard Mellein, and Alberto Gimona, and Patrice Matchaba, and Christopher J Hawkey, and James H Chesebro, and

Cardiovascular Clinical Research Center, New York University School of Medicine, 530 First Avenue, New York, NY 10016, USA. michael.farkouh@med.nyu.edu

BACKGROUND The potential for cyclo-oxygenase 2 (COX2)-selective inhibitors to increase the risk for myocardial infarction is controversial. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs, naproxen and ibuprofen. METHODS 18325 patients age 50 years or older with osteoarthritis were randomised to lumiracoxib 400 mg once daily (n=9156), naproxen 500 mg twice daily (4754), or ibuprofen 800 mg three times daily (4415) in two substudies of identical design. Randomisation was stratified for low-dose aspirin use and age. The primary cardiovascular endpoint was the Antiplatelet Trialists' Collaboration endpoint of non-fatal and silent myocardial infarction, stroke, or cardiovascular death. Analysis was by intention to treat. RESULTS 81 (0.44%) patients did not start treatment and 7120 (39%) did not complete the study. At 1-year follow-up, incidence of the primary endpoint was low, both with lumiracoxib (59 events [0.65%]) and the non-steroidal anti-inflammatory drugs (50 events [0.55%]; hazard ratio 1.14 [95% CI 0.78-1.66], p=0.5074). Incidence of myocardial infarction (clinical and silent) in the overall population in the individual substudies was 0.38% with lumiracoxib (18 events) versus 0.21% with naproxen (ten) and 0.11% with lumiracoxib (five) versus 0.16% with ibuprofen (seven). In the naproxen substudy, rates of myocardial infarction (clinical and silent) did not differ significantly compared with lumiracoxib in the population not taking low-dose aspirin (hazard ratio 2.37 [95% CI 0.74-7.55], p=0.1454), overall (1.77 [0.82-3.84], p=0.1471), and in patients taking aspirin (1.36 [0.47-3.93], p=0.5658). In the ibuprofen substudy, these rates did not differ between lumiracoxib and ibuprofen in the population not taking low-dose aspirin (0.75 [0.20-2.79], p=0.6669), overall (0.66 [0.21-2.09], p=0.4833), and in patients taking aspirin (0.47 [0.04-5.14], p=0.5328). CONCLUSIONS The primary endpoint, including incidence of myocardial infarction, did not differ between lumiracoxib and either ibuprofen or naproxen, irrespective of aspirin use. This finding suggests that lumiracoxib is an appropriate treatment for patients with osteoarthritis, who are often at high cardiovascular risk and taking low-dose aspirin.

UI	MeSH Term	Description	Entries
D007052	Ibuprofen	A non-steroidal anti-inflammatory agent with analgesic, antipyretic, and anti-inflammatory properties	Advil,Benzeneacetic Acid, alpha-methyl-4-(2-methylpropyl)- trimethylsilyl ester,Brufen,Ibumetin,Ibuprofen, (+-)-Isomer,Ibuprofen, (R)-Isomer,Ibuprofen, (S)-Isomer,Ibuprofen, Aluminum Salt,Ibuprofen, Calcium Salt,Ibuprofen, Copper (2+) Salt,Ibuprofen, Magnesium Salt,Ibuprofen, Potassium Salt,Ibuprofen, Sodium Salt,Ibuprofen, Zinc Salt,Ibuprofen-Zinc,Motrin,Nuprin,Rufen,Salprofen,Trauma-Dolgit Gel,alpha-Methyl-4-(2-methylpropyl)benzeneacetic Acid,Ibuprofen Zinc,Trauma Dolgit Gel
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009203	Myocardial Infarction	NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).	Cardiovascular Stroke,Heart Attack,Myocardial Infarct,Cardiovascular Strokes,Heart Attacks,Infarct, Myocardial,Infarction, Myocardial,Infarctions, Myocardial,Infarcts, Myocardial,Myocardial Infarctions,Myocardial Infarcts,Stroke, Cardiovascular,Strokes, Cardiovascular
D009288	Naproxen	An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout.	Aleve,Anaprox,Methoxypropiocin,Naprosin,Naprosyn,Naproxen Sodium,Proxen,Sodium Naproxenate,Synflex,Naproxenate, Sodium,Sodium, Naproxen
D009930	Organic Chemicals	A broad class of substances containing carbon and its derivatives. Many of these chemicals will frequently contain hydrogen with or without oxygen, nitrogen, sulfur, phosphorus, and other elements. They exist in either carbon chain or carbon ring form.	Organic Chemical,Chemical, Organic,Chemicals, Organic
D010003	Osteoarthritis	A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.	Arthritis, Degenerative,Osteoarthrosis,Osteoarthrosis Deformans,Arthroses,Arthrosis,Arthritides, Degenerative,Degenerative Arthritides,Degenerative Arthritis,Osteoarthritides,Osteoarthroses
D010975	Platelet Aggregation Inhibitors	Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.	Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D004008	Diclofenac	A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.	Diclophenac,Dichlofenal,Diclofenac Potassium,Diclofenac Sodium,Diclonate P,Dicrofenac,Feloran,GP-45,840,Novapirina,Orthofen,Orthophen,Ortofen,SR-38,Sodium Diclofenac,Voltaren,Voltarol,Diclofenac, Sodium,GP 45,840,GP45,840,SR 38,SR38
D004311	Double-Blind Method	A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment.	Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked