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

Abstract

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.

FINDINGS:

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).

INTERPRETATION:

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.

• Authors: Michael E Farkouh, Howard Kirshner, Robert A Harrington, Sean Ruland, Freek W A Verheugt, Thomas J Schnitzer, Gerd R Burmester, Eduardo Mysler, Marc C Hochberg, Michael Doherty, Elena Ehrsam, Xavier Gitton, Gerhard Krammer, Bernhard Mellein, Alberto Gimona, Patrice Matchaba, Christopher J Hawkey, James H Chesebro, TARGET Study Group
• Journal: Lancet (London, England) (Lancet) 2004 Aug 21-27 Vol. 364 Issue 9435 Pg. 675-84 ISSN: 1474-547X [Electronic] England
• PMID: 15325832 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase Inhibitors
• Organic Chemicals
• Platelet Aggregation Inhibitors
• Diclofenac
• Naproxen
• Aspirin
• lumiracoxib
• Ibuprofen

Topics

• Aged
• Anti-Inflammatory Agents, Non-Steroidal (adverse effects, therapeutic use)
• Aspirin (administration & dosage, adverse effects)
• Cyclooxygenase Inhibitors (adverse effects, therapeutic use)
• Diclofenac (analogs & derivatives)
• Double-Blind Method
• Female
• Humans
• Ibuprofen (adverse effects, therapeutic use)
• Male
• Middle Aged
• Myocardial Infarction (chemically induced)
• Naproxen (adverse effects, therapeutic use)
• Organic Chemicals (adverse effects, therapeutic use)
• Osteoarthritis (drug therapy)
• Platelet Aggregation Inhibitors (administration & dosage, adverse effects)
• Risk Factors
• Stroke (chemically induced)