Source: Hepatology  |  Posted 9 years ago

Doctors must now view with caution earlier pooled estimates of the effects of patient and drug variables on risk of serious upper gastrointestinal complications from nonsteroidal anti-inflammatory drug use.

Contrary to earlier indications, these complications and use of nonsteroidal anti-inflammatory drugs (NSAIDs) are linked, a massive analysis has found.

Until now, meta-analyses in this area have focused on published English-language epidemiologic literature and/or only a portion of the relevant evidence; these are restrictions now known to be linked with bias in this type of analysis.

To determine the least biased estimates of risks of perforations, ulcers, and bleeds (PUB) linked with NSAID use, this meta-analysis synthesized published and unpublished evidence from all study designs and all languages between 1966 and 1998.

As well as using NSAID studies reporting primary data on GI complications, researchers hand-searched new drug application reviews from the United States Food and Drug Administration to identify unpublished studies with inclusion criteria identical to those used for published reports.

Selected studies had to assess use of oral NSAID use for more than four days in subjects more than 18 years of age and report on the clinically relevant upper GI outcomes of PUB. Most clinical trials were found to be of good quality, but observational studies had methodologic limitations.

The pooled odds ratio (OR) from 16 NSAID versus placebo clinical trials (4,431 patients) was found to be 5.36. Pooled relative risk of PUB from nine cohort studies (more than 750,000 person-years of exposure) was 2.7.
From 23 case control studies using age and sex matching (representing 25,732 patients) the pooled OR of PUB was 3.0.

Although data were insufficient to justify subgroup analyses stratified by age, comorbid conditions, drug or dose, they do support an association between NSAID use and serious upper GI complications, including estimates from different study designs.

Thus prior pooled estimates about the effect of patient and drug variables on increased risk must be viewed with caution, these authors conclude.