Cardiovascular safety of lumiracoxib: a meta-analysis of all randomized controlled trials > or =1 week and up to 1 year in duration of patients with osteoarthritis and rheumatoid arthritis.

Abstract

BACKGROUND:

The cardiovascular (CV) safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 inhibitors has been the subject of considerable debate.

OBJECTIVE:

The objective of this study was to determine the risk of CV events with lumiracoxib by meta-analysis of all completed, randomized controlled trials (RCTs) of > or =1 week and up to 1 year in duration of patients with osteoarthritis and rheumatoid arthritis.

METHODS:

The Novartis Lumiracoxib Clinical Trial Database, which includes all clinical studies conducted to date with lumiracoxib, was reviewed. Data were extracted from RCTs of > or =1 week and up to 1 year in duration, the maximum study duration; 34,668 patients were included in standard and cumulative meta-analyses. Twenty-two RCTs of lumiracoxib 100 to 1200 mg daily were identified; 22,781 patients were included in 1-year trials. Mean age of the patients was 61.5 years and 74% were female. More than 50% of the patients in these studies had hypertension at baseline and 6% had diabetes. Parameters analyzed were the Antiplatelet Trialists' Collaboration (APTC) composite CV end point of myocardial infarction (MI), stroke (ischemic and hemorrhagic), and CV death; MI alone; and stroke alone. Twenty-one of the 22 RCTs have been published.

RESULTS:

For all 3 parameters, relative risk (RR) was calculated versus non-naproxen NSAIDs, naproxen, and placebo. The results were as follows: for the APTC end point versus non-naproxen NSAIDs: RR 0.83, 95% CI, 0.46-1.51; versus naproxen: RR 1.49, 95% CI, 0.94-2.36; versus placebo: RR 1.08, 95% CI, 0.41-2.86; for MI alone versus non-naproxen NSAIDs: RR 0.80, 95% CI, 0.28-2.25; versus naproxen: RR 1.69, 95% CI, 0.82-3.48; versus placebo: RR 1.27, 95% CI, 0.25-6.56; and for stroke alone versus non-naproxen NSAIDs: RR 0.91, 95% CI, 0.35-2.35; versus naproxen: RR 1.42, 95% CI, 0.70-2.91; versus placebo: RR 0.59, 95% CI, 0.13-2.74. Cumulative meta-analyses of lumiracoxib versus all comparators (placebo, diclofenac, ibuprofen, celecoxib, rofecoxib, and naproxen) did not find any significant differences in APTC, MI alone, or stroke alone.

CONCLUSION:

This meta-analysis of 34,668 patients receiving > or =1 week and up to 1 year of treatment found no evidence that lumiracoxib was associated with a significant increase in CV risk compared with naproxen, placebo, or all comparators (placebo, diclofenac, ibuprofen, celecoxib, rofecoxib, and naproxen).

• Authors: Patrice Matchaba, Xavier Gitton, Gerhard Krammer, Elena Ehrsam, Victor Schorr Sloan, Melvin Olson, Bernhard Mellein, Godehard Hoexter, John Orloff, Jean-Jacques Garaud
• Journal: Clinical therapeutics (Clin Ther) Vol. 27 Issue 8 Pg. 1196-214 (Aug 2005) ISSN: 0149-2918 [Print] United States
• PMID: 16199245 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase 2 Inhibitors
• Organic Chemicals
• Diclofenac
• lumiracoxib

Topics

• Anti-Inflammatory Agents, Non-Steroidal (adverse effects, therapeutic use)
• Arthritis, Rheumatoid (drug therapy)
• Cardiovascular Diseases (chemically induced)
• Cyclooxygenase 2 Inhibitors (adverse effects, therapeutic use)
• Databases, Factual
• Diclofenac (analogs & derivatives)
• Female
• Humans
• Male
• Middle Aged
• Organic Chemicals (adverse effects, therapeutic use)
• Osteoarthritis (drug therapy)
• Randomized Controlled Trials as Topic (statistics & numerical data)