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Review
. 2004 Jul;63(7):759-66.
doi: 10.1136/ard.2003.015925.

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

F Richy  1 , O Bruyere, O Ethgen, V Rabenda, G Bouvenot, M Audran, G Herrero-Beaumont, A Moore, R Eliakim, M Haim, J-Y Reginster
Affiliations
Review

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

F Richy et al. Ann Rheum Dis. 2004 Jul.

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.

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Figures

Figure 1
Figure 1
Relative risk of GI complications depending on NSAID (RCT).
Figure 4
Figure 4
Relative risk of GI complications provided by longitudinal controlled cohort studies. PUB, perforation, ulcers, or bleeding.
Figure 2
Figure 2
Meta-regression of relative risk against study duration (non-indometacin compounds).
Figure 3
Figure 3
Meta-regression of relative risk against study duration (indometacin).
Figure 5
Figure 5
Funnel plot.
See this image and copyright information in PMC

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