Table 1 Characteristics of RCTs and summary of effects of aspirin on the incidence of recurrent colorectal adenomas

Baron 2003 (Aspirin/Folate Polyp Prevention Study (AFPPS)) [12]

United States

≈3 years (3 years after the baseline examination)

Age - range, 21–81 years; % male: 64; subjects with history of adenomas; and documented clean colon post-polypectomy

Aspirin 81 mg/day (n = 169); aspirin 325 mg/day (n = 167); aspirin 81 mg/day and folic acid 1 mg/day (n = 175); aspirin 325 mg/day and folic acid 1 mg/day (n = 171); folic acid 1 mg/day (n = 170); placebo (n = 169).

Primary outcome: recurrent colorectal adenomas

Secondary outcomes: numbers of colorectal adenomas and advanced adenomas (defined as those with tubule-villous adenomas (25 to 75% villous features), villous adenomas (more than 75% villous), large adenomas (at least 1 cm in diameter), severe dysplasia, or invasive cancer)

3% excluded from analysis as no follow-up colonoscopy

Aspirin any dose- 91.7 (18.8); aspirin 81 mg- 91.9 (18.8); aspirin 325 mg- 91.6 (18.7); placebo- 90.3 (20.5)

Unadjusted relative Risk (95% CI):

Aspirin any dose versus placebo

Any adenoma: 0.88 (0.77–1.02)

Advanced adenoma: 0.71 (0.50–1.00)

Aspirin 81 mg versus placebo

Any adenoma: 0.81 (0.69–0.96)

Advanced adenoma: 0.59 (0.38–0.92)

Aspirin 325 mg versus placebo

Any adenoma: 0.96 (0.81–1.13)

Advanced adenoma: 0.83 (0.55–1.23)

Sandler 2003 (The colorectal adenoma preventions study [Cancer and Leukemia Group B (CALGB) 9270] [15]

United States

≈3 years (Participants with early-stage disease at 4 years and all other participants at 3 years after the baseline examination)

Ages – range, 30–80 years; % male: 52; subjects with of histologically documented colon or rectal cancer with a low risk of recurrent disease; and documented clean colon post-polypectomy

Aspirin 325 mg/day (n = 317); placebo (n = 318)

Primary outcome: incidence of adenoma.

Secondary outcomes: the size of the largest adenoma; the time to the detection of a first adenoma, and the proportion of patients with advanced adenomas (defined as those that were at least 1 cm in diameter or had villous components)

19% excluded from analysis as no follow-up colonoscopy

Aspirin- 79.4 (26.8); placebo- 74.9 (28.5)

Adjusted relative risk (95% CI)

Aspirin 325 mg versus placebo

Any adenoma: 0.65 (0.46–0.91)

Advanced adenoma: Not reported in the study.

Risk ratio reported by Cole et al. [8] -0.77 (0.29–2.05)

Logan 2008, (United Kingdom Colorectal Adenoma Prevention (ukCAP) trial) [14]

United Kingdom and Denmark

3 years (3 years after the baseline examination)

Age – mean,58 years; range, 28–75 years; % male: 56; subjects with history of colorectal adenoma 0.5 cm or greater; and documented clean colon post-polypectomy

Aspirin 300 mg/day (n = 236); folic acid 0.5 mg/day (n = 234); aspirin 300 mg/day and folic acid 0.5 mg/day (n = 236); placebo (n = 233)

Primary outcome: recurrent colorectal adenomas

Secondary outcomes: number of adenomas detected and incidence of advanced colorectal neoplasia (advanced colorectal neoplasia defined as adenomas that were either 1 cm or larger in diameter, villous or tubule-villous, or showed severe dysplasia or invasive cancer)

10% excluded from analysis as no follow-up colonoscopy

Aspirin- 77.1 (35.2); placebo- 80.9 (31.6)

Relative Risk (95% CI) - Aspirin 300 mg versus placebo

Any adenoma: 0.79 (0.63–0.99)

Advanced adenoma: 0.63 (0.43–0.91)

Benamouzig 2012 (Association pour la Prevention par l’ Aspirine du Cancer Colorectal (APACC) Study-4 year results) [17]

France

4 years (4 years after the baseline examination)

Age – range, 18–75 years; % male: 70; subjects with history of at least 3 adenomas irrespective of size, or at least one measuring 6 mm in diameter or more; and documented clean colon post-polypectomy

Aspirin 160 mg/day (n = 73); aspirin 300 mg/day (n = 67); placebo (n = 132)

(Aspirin ≈ lysine acetylsalicylate)

Primary outcomes: recurrent colorectal adenomas, and the adenomatous polyp burden

Secondary outcomes: mean numbers of recurrent adenomas and numbers of recurrent advanced adenomas (defined as those with a maximum diameter of at least 10 mm, at least 25% villous elements or evidence of high-grade dysplasia)

32% excluded from analysis as no follow-up colonoscopy at year 4

Aspirin – 88 (26);

placebo- 88 (26)

Aspirin any dose versus placebo (Relative risk, not reported)

Any adenoma: Aspirin at any dose-42/102 (41%); Aspirin 160 mg-15/55 (27%); Aspirin 300 mg – 27/47 (57%); Placebo-33/83 (40%); non-significant.

Advanced adenoma: Aspirin at any dose-10/182 (10%); Aspirin 160 mg-6/55 (11%); Aspirin 300 mg – 4/47 (8.5%); Placebo-7/83 (7%); non-significant.

Ishikawa 2014 [16]

Japan

2 years (2 years after the baseline examination)

Age - range, 40–70 years; % male: 79; subjects with history of colorectal adenomas and/or adenocarcinomas with invasions confined to the mucosa; and documented clean colon post-polypectomy

Aspirin (enteric-coated) 100 mg/day (n = 191); placebo (n = 198).

Primary outcome: incidence of adenoma or adenocarcinoma recurrence (advanced adenomas defined as high-grade dysplasias)

Secondary outcomes: recurring tumor number, size and histology as well as the effects of lifestyle, such as smoking and alcohol drinking, and the frequency of adverse effects

not available

(Stated “no significant difference between the two groups in compliance rates”)

Adjusted odds ratio (OR)

Aspirin 100 mg versus placebo

Any adenoma (reported as colorectal tumour): 0.60 (95% CI 0.36 to 0.98)

Advanced adenoma: Adjusted OR not reported. [Reported incidence of high grade dysplasia: Aspirin-1/152 (0.7%); Placebo-2/159 (1.3%)]