A randomised, placebo-controlled 2 × 2 factorial trial of EPA free fatty acid (FFA) 2 g daily (E; either as the FFA or triglyceride [TG]) and/or aspirin 300 mg daily (A) in ‘high risk’ patients (≥3 adenomas if one≥10 mm, or ≥5 small adenomas) identified at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). The primary endpoint was the adenoma detection rate (ADRa; the% with any adenoma) at one year surveillance colonoscopy. Secondary endpoints included mean number of adenomas per patient (MAP), ‘advanced’ ADRa, adenoma location (right/left) and type (conventional/serrated). Analysis was on an intention-to-treat basis using an ‘at the margins’ approach, adjusted for BCSP site and repeat endoscopy at baseline.Methods
We recruited 709 participants (80% male, mean[SD] 65 years, 82% BMI >25 Kg/m2). The four treatment groups (E+A n=177; E n=178; A n=176; placebo n=176) were well-matched at baseline. There were no differences in EPA levels or tolerability between FFA and TG users. Overall, ADRa was 62%, with no evidence of any effect for EPA (risk ratio 0.98 [95% CI 0.87–1.12]) or aspirin (0.99 [0.87–1.12]). Aspirin use was associated with reduced total MAP (incidence rate ratio 0.78 [95%CI 0.68–0.90]), with evidence of an effect on serrated (0.46 [0.25–0.87]) and right-sided (0.73 [0.61–0.88]) lesions. Evidence that EPA reduced MAP was restricted to conventional (0.86 [0.74–0.99]), left-sided (0.75 [0.60–0.94]) adenomas, but not total MAP (0.91 [0.79–1.05]). EPA and aspirin treatment were well tolerated with an excess of mild-moderate GI adverse events (AEs), especially in the E arm. There were 6 bleeding AEs across the treatment arms.Methods
Neither EPA nor aspirin treatment was associated with reduction in the ADRa in ‘high risk’ patients. Secondary analyses revealed no evidence that EPA was effective in reducing the total number of adenomas, but there was some evidence for efficacy of aspirin. Both agents displayed effects on MAP, which were adenoma type- and site-specific, compatible with known anti-(proximal) CRC activity of aspirin. Best use of EPA and aspirin may need a precision medicine approach to adenoma recurrence. ISRCTN05926847 – This project was funded by the EME Programme, an MRC and NIHR partnership. The views expressed in this publication are those of the author(s) and not necessarily those of the MRC, NHS, NIHR or the DoH.