Abstract
BackgroundBeneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Uncertainty remains about the appropriate dose of aspirin for adenoma prevention. The persistence of the protective effect of NSAIDs against recurrent adenomas after treatment cessation is yet to be established.MethodsOur objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA).ResultsIn patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80–160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70–0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44–0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300–325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68–1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59–0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33–0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal.ConclusionOur findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.
Highlights
Beneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; the results have not been conclusive
In summary, the available randomized trials suggest that aspirin and cyclooxygenase- 2 (COX-2) inhibitors reduce the risk of recurrence of colorectal adenomas in patients with a previous history of colorectal cancer or adenomas
The accumulated evidence for aspirin is associated with fewer risks of systematic errors as well as random errors
Summary
Beneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; the results have not been conclusive. Favourable effect of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase- 2 (COX-2) inhibitors, on recurrent colorectal adenomas have been reported in many observational studies and randomized controlled trials (RCTs) [4,5,6]. Published systematic reviews [5,6,7] and meta-analyses [8,9,10,11] based on the results from RCTs [12,13,14,15,16,17] propose that aspirin at any doses decreases the risk of recurrent colorectal adenomas. Previous two meta-analyses [8, 9], demonstrated a moderate beneficial effect of low-dose aspirin on preventing recurrent adenomas.
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