Time dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta-analytic approach

Abstract

Objectives: To provide an updated document assessing the global, NSAID-specific, and time dependent risk of gastrointestinal (GI) complications through meta-analyses of high quality studies. Methods: An exhaustive systematic search was performed. Inclusion criteria were: RCT or controlled study, duration of 5 days at least, inactive control, assessment of minor or major NSAID adverse effects, publication range January 1985 to January 2003. The publications retrieved were assessed during a specifically dedicated WHO meeting including leading experts in all related fields. Statistics were performed conservatively. Meta-regression was performed by regressing NSAID adjusted estimates against study duration categories. Results: Among RCT data, indolic derivates provided a significantly higher risk of GI complications related to NSAID use than for non-users: RR = 2.25 (1.00; 5.08) than did other compounds: naproxen: RR = 1.83 (1.25; 2.68); diclofenac: RR = 1.73 (1.21; 2.46); piroxicam: RR = 1.66 (1.14; 2.44); tenoxicam: RR = 1.43 (0.40; 5.14); meloxicam: RR = 1.24 (0.98; 1.56), and ibuprofen: RR = 1.19 (0.93; 1.54). Indometacin users had a maximum relative risk for complication at 14 days. The other compounds presented a better profile, with a maximum risk at 50 days. Significant additional risk factors included age, dose, and underlying disease. The controlled cohort studies provided higher estimates: RR = 2.22 (1.7; 2.9). Publication bias testing was significant, towards a selective publication of deleterious effects of NSAIDs from small sized studies. Conclusion: This meta-analysis characterised the ''compound'' and ''time'' aspects of the GI toxicity of non-selective NSAIDs. The risk/benefit ratio of such compounds should thus be carefully and individually evaluated at the start of long term treatment. N on-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain, fever, and inflammation. The worldwide NSAID market for both occasional and chronic users has been conservatively estimated at over 60 million people, and some NSAIDs (aspirin, naproxen, ibuprofen, etc) are among the most popular over the counter drugs.1 2 Chronic NSAID treatment effectively reduces the symptoms of many painful arthritic syndromes, but induces adverse gastrointestinal (GI) complications, ranging from abdominal discomfort to life threatening GI ulceration, bleeding, and perforation. Indeed, through their non-specific inhibition of the two cyclo-oxygenase isoenzymes, both aspirin and conventional NSAIDs induce gastroduodenal damage, 5 6 and are now considered as a major cause of iatrogenic pathology. 7 The most common clinical manifestations of NSAID related GI damage to tissue are a combination of gastroduodenal erosions and ulcerations, often called NSAID induced gastropathy, 4 affecting 25-50% of chronic NSAID users. NSAID induced gastropathy may limit long term NSAID treatment and causes a significant financial burden to the healthcare system. 4 8 9In the late 1980s and 1990s, drug related adverse reactions ...

The selective and non-selective cyclooxygenase inhibitors valdecoxib and piroxicam induce the same postoperative analgesia and control of trismus and swelling after lower third molar removal

“…However, taking into account the short-term treatment with valdecoxib and piroxicam (4 days), both drugs were safe for our patients. Piroxicam requires more than 1 month to induce deleterious gastrointestinal side effects, with a maximum risk at 50 days (37).…”

Prevention of nonsteroidal anti-inflammatory drug-induced gastropathy

“…In 2004, the World Health Organization (WHO) conducted a meta-analysis of major trials and published a consensus statement in which the risk of GI complications ascribed to specifi c NSAIDs was, in descending order, indomethacin [relative risk (RR) 2.25], naproxen (RR 1.83), diclofenac (RR 1.73), piroxicam (RR 1.66), tenoxicam (RR 1.43), ibuprofen (RR 1.43), and meloxicam (RR 1.24). 35 Etodolac and salsalate, which are believed to cause less GI toxicity than any of the aforementioned NSAIDs, were unfortunately not included in this review. Pharmacokinetics may also infl uence the risk of bleeding, with short-acting NSAIDs thought to have less toxicity than long-acting agents.…”

Relative Value of the NSAIDs, Including COX-2 Inhibitors and Meloxicam

“…21 For NSAID users compared with nonusers, the relative risk of GI complications in the RCTs was 1.83 (1.25-2.68) for naproxen, 1.73 (1.21-2.46) for diclofenac, 1.24 (0.98-1.56) for meloxicam, and 1.19 (0.93-1.54) for ibuprofen.…”