Risk of serious NSAID-related gastrointestinal events during long-term exposure: a systematic review.
OBJECTIVE
Exposure to non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of serious gastrointestinal (GI) events compared with non-exposure. We investigated whether that risk is sustained over time.


METHODS
Cochrane Controlled Trials Register (to 2002); MEDLINE, EMBASE, Derwent Drug File and Current Contents (1999-2002); manual searching of reviews (1999-2002).


METHODS
From 479 search results reviewed and 221 articles retrieved, seven studies of patients exposed to prescription non-selective NSAIDs for more than 6 months and reporting time-dependent serious GI event rates were selected for quantitative data synthesis. These were stratified into two groups by study design.


METHODS
Incidence of GI events and number of patients at specific time points were extracted.


RESULTS
Meta-regression analyses were performed. Change in risk was evaluated by testing whether the slope of the regression line declined over time. Four randomised controlled trials (RCTs) provided evaluable data from five NSAID arms (aspirin, naproxen, two ibuprofen arms, and diclofenac). When the RCT data were combined, a small significant decline in annualised risk was seen: - 0.005% (95% CI, - 0.008% to - 0.001%) per month. Sensitivity analyses were conducted because there was disparity within the RCT data. The pooled estimate from three cohort studies showed no significant decline in annualised risk over periods up to 2 years: - 0.003% (95% CI, - 0.008% to 0.003%) per month.


CONCLUSIONS
Small decreases in risk over time were observed; these were of negligible clinical importance. For patients who need long-term (> 6 months) treatment, precautionary measures should be considered to reduce the net probability of serious GI events over the anticipated treatment duration. The effect of intermittent versus regular daily therapy on long-term risk needs further investigation.
Schaffer
Delia
D
Pfizer Australia, Sydney, NSW, Australia. delia.schaffer@pfizer.com
Florin
Timothy
T
Eagle
Craig
C
Marschner
Ian
I
Singh
Gurkirpal
G
Grobler
Mendel
M
Fenn
Chris
C
Schou
Manjula
M
Curnow
Kathleen M
KM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D018570:Risk Assessment; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal