Low-dose aspirin safely suppresses the recurrence of colorectal polyps larger than 5.0 mm in patients with familial adenomatous polyposis (FAP), according to a study in Lancet Gastroenterology & Hepatology.
The randomized, double-blind, placebo-controlled J-FAPP Study IV trial was conducted in 11 hospitals and outpatient clinics in Japan. Eligible patients were aged 16 to 70 years with more than 100 adenomatous polyps in the large intestine and no history of colectomy. All patients had undergone endoscopic removal of colorectal polyps that were at least 5.0 mm in diameter.
Participants were assigned to 1 of 4 groups: aspirin (100 mg per day) plus mesalazine (2 g per day); aspirin (100 mg per day) plus mesalazine placebo; aspirin placebo plus mesalazine (2 g per day); or aspirin placebo plus mesalazine placebo. Treatment was continued until 1 week before the colonoscopy at 8 months. The investigators balanced the groups for sex, age (<30 years vs ≥30 years), and smoking status.
A total of 104 patients underwent pre-intervention colonoscopy, and 26 patients were assigned to each of the 4 groups. After 2 patients in the aspirin plus placebo group were excluded, the remaining 102 participants completed the study and underwent a colonoscopy at 8 months.
In the intention-to-treat analysis, 15 (30%) patients who received aspirin (aspirin plus mesalazine group and aspirin plus placebo group) had colon polyps of at least 5.0 mm, compared with 26 (50%) patients who received either no aspirin or mesalazine plus placebo. The crude odds ratio (OR) was 0.43 (95% CI, 0.19-0.97) for any aspirin use, which indicated a protective effect of low-dose aspirin. The adjusted OR for age and sex was 0.37 (95% CI, 0.16-0.86).
For participants who received any mesalazine (mesalazine plus placebo or aspirin plus mesalazine) in the intention-to-treat analysis, 20 (38%) patients had colon polyps of at least 5.0 mm, compared with 21 (42%) patients who did not receive mesalazine (participants in the no mesalazine group and those in the aspirin plus placebo group). The crude OR was 0.87 (95% CI, 0.39-1.96), and the adjusted OR for age and sex was 0.87 (95% CI, 0.38-1.99). No interaction was observed between aspirin and mesalazine (P =.64).
Regarding adverse events, the most common were grades 1-2 upper gastrointestinal symptoms in 3 of 26 (12%) patients who received aspirin plus mesalazine, 1 of 24 (4%) patients who received aspirin plus mesalazine placebo, and 1 of 26 (4%) patients who received mesalazine plus aspirin placebo. In the mesalazine plus aspirin placebo group, 1 grade 4 event of liver dysfunction occurred but was not related to treatment.
Among several study limitations, aspirin was administered for only 8 months and the effect of other doses was not investigated. Additionally, all patients were Japanese, and ethnicity might be a key factor in colorectal adenoma and the weight-dependent effects of aspirin.
“Because colorectal polyps larger than 5.0 mm strongly correlate with the development of colorectal cancer, low-dose aspirin could be a useful chemopreventive drug for colorectal cancer prevention in patients with FAP,” stated the researchers.
Disclosures: Some of the authors reported affiliations with pharmaceutical and medical device companies. Please see the original reference for a full list of disclosures.
Ishikawa H, Mutoh M, Sato Y, et al. Chemoprevention with low-dose aspirin, mesalazine, or both in patients with familial adenomatous polyposis without previous colectomy (J-FAPP Study IV): a multicentre, double-blind, randomised, two-by-two factorial design trial. Lancet Gastroenterol Hepatol. Published online April 1, 2021. doi: 10.1016/S2468-1253(21)00018-2