Aspirin and NSAIDs in preventing colorectal adenoma

A meta-analysis in 2014 in the Annals of Oncology (1a) added to the evidence base for a reduction in cancer risk with aspirin use (1):

They found that protection against cancer starts to become apparent after taking low-dose aspirin for 3 years, and a protective effect against cancer mortality is seen after 5 years

Calculated that if an adult aged 50 to 65 were to take aspirin for 10 years

• would be a 7% (women) to 9% (men) relative risk reduction in the number of cancer, myocardial infarction or cerebrovascular accident events over a 15-year period
• the effect was most pronounced in colorectal cancer, where it reduced incidence by 35% and mortality by 40%
• in oesophageal cancer, incidence was reduced by 30% and mortality by 50%, and in gastric cancer these decreased by 30% and 35%, respectively
• also found strong evidence of a smaller effect on some other cancers
  • aspirin reduced the incidence of lung cancer by around 5% and mortality by 15%, in prostate cancer incidence fell by 10% and mortality by 15%, and in breast cancer incidence reduced by 10% and mortality by 5%
• risks of bleeding are predictably increased

Absolute reductions are obviously sex and age dependent, but they calculate that if 1,000 people aged 60 took the drug for 10 years, a further decade later (i.e. by the time they were aged 80) there would be:

• 16 fewer deaths from cancer (NNT 63 over 10 years), 1 less death from heart attack, 2 extra deaths from bleeding (NNH 500 over 10 years)

Conclusion:

• analysis of benefits and harms in the general population suggests net benefit for cancer prevention and reduced mortality, for a minimum of 5 years of aspirin prophylaxis between the ages of 50 and 65 with larger benefits for up to 10 years of use. In particular, 'there is now overwhelming evidence for a reduction in colorectal cancer incidence and mortality from regular aspirin use'...authors claim their findings have public health potential; they estimate that if everyone over 50 took low-dose aspirin for 10 years, 122,000 deaths would be prevented over 2 decades. Helicobacter pylori (present in 20% of people aged over 60) doubles the risk of bleeding due to aspirin, and the authors propose further research to look at the effectiveness of checking for HP before starting low-dose aspirin

Aspirin and colon cancer

There is evidence relating to the effectiveness of aspirin as a chemoprophylaxis in people with a history of previous colorectal adenomas (2) and people with a history of previous colorectal cancer (3).

• in persons at risk (recent history of histologically documented adenomas)

• in patients with previous colorectal cancer

Notes:

• a review (4) based on data from three pooled randomized controlled trials provided evidence that aspirin and NSAIDs significantly reduces the recurrence of sporadic adenomatous polyps after one to three years
  • there is evidence from short-term studies to support regression, but not elimination or prevention of colorectal adenomas in familial adenomatous polyposis
• a systematic review (5) concluded that aspirin appears to be effective at reducing the incidence of colonic adenoma and colorectal cancer, especially if used in high doses for more than 10 years. The review included observational studies and randomized controlled trials - however the randomized controlled trials failed to show a protective effect
• a review of randomised and observational studies concluded that use of 300 mg or more of aspirin a day for about 5 years is effective in primary prevention of colorectal cancer in randomised controlled trials, with a latency of about 10 years, which is consistent with findings from observational studies (6)
• a Chinese cohort study (n=49,679) found low-dose aspirin reduced risks of colorectal cancer and gastric cancer but increased the risk of gastrointestinal bleeding. Use of proton pump inhibitors or histamine H2-receptor antagonists eliminated the increased bleeding risk (7)
• researchers used several population-based registries to identify individuals aged ≥ 50 years living in Norway between 2014 and 2018, excluding those with a prior history of invasive cancer or who had lived in Norway for less than 6 months before study commencement (8)
  • follow-up began 6 months after entering the cohort and continued until CRC diagnosis, another cancer diagnosis, death, emigration, or the end of follow-up on December 31, 2018
  • 2,186,390 individuals included, 38,577 (1.8%) were diagnosed with CRC after a median follow-up of 10.9 years
    • low-dose aspirin was used at least once by 579,196 (26.5%) individuals
    • compared with never-use, current aspirin use was associated with a lower CRC risk (hazard ratio [HR], 0.87), an association that was more pronounced for metastatic CRC (HR, 0.79) than for regionally advanced (HR, 0.89) and localized disease (HR, 0.93)
    • duration of current aspirin use was also associated with the degree of CRC risk, at HRs of 0.91 for < 3 years, 0.85 for ≥ 3 and < 5 years, and 0.84 for ≥ 5 years
    • estimated that aspirin use averted 1073 cases of CRC over the study period
• study evidence suggests that regular aspirin use may have an active role in enhancing immunosurveillance against CRC (9)
• aspirin use and reduction in CRC risk in relation to additional risk factors (10)
  • cohort study of 107 655 men and women receiving aspirin and followed up for more than 3 decades
    • showed that the absolute reduction in CRC risk was more pronounced among those with an unhealthier lifestyle (ie, higher body mass index, greater amount of smoking, higher alcohol intake, less physical activity, and poorer diet quality) compared with those with a healthier lifestyle
    • in contrast, the relative reduction in CRC risk associated with aspirin use was similar

• findings of the study suggest that lifestyle risk factors may be useful to identify individuals who may have a more favorable risk-benefit profile for cancer prevention with aspirin

Reference:

1. Torjesen I. Daily aspirin reduces risk of developing and dying from cancer, researchers find. BMJ 2014 Aug 5;349:g5037.
2. Baron JA et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348:891-9.
3. Sandler RS et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003; 348: 883-90.
4. Asanon T, McLeod R. Non steroidal anti-inflammatory drugs (NSAID) and Aspirin for preventing colorectal adenomas and carcinomas. Cochrane Database Syst REv 2004; (2):CD004079
5. Dube C et al. The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force.Ann Intern Med. 2007 Mar 6;146(5):365-75.
6. Flossmann E et al. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies.Lancet. 2007 May 12;369(9573):1603-13.
7. Shami JJP, Zhao J, Pathadka S, et al. Safety and effectiveness of low-dose aspirin for the prevention of gastrointestinal cancer in adults without atherosclerotic cardiovascular disease: a population-based cohort study. BMJ Open 2022;12:e050510. doi: 10.1136/bmjopen-2021-050510.
8. Nafisi S et al. Low-dose aspirin and prevention of colorectal cancer: evidence from a nationwide registry-based cohort in Norway. The American Journal of Gastroenterology ():10.14309/ajg.0000000000002695, February 01, 2024. DOI: 10.14309/ajg.0000000000002695
9. Simoni OD, Scarpa M, Castagliuolo I, et al. IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer. Cancer. 2024; 130(13): 2272-2286. doi:10.1002/cncr.35297 (https://doi.org/10.1002/cncr.35297)
10. Sikavi DR, Wang K, Ma W, et al. Aspirin Use and Incidence of Colorectal Cancer According to Lifestyle Risk. JAMA Oncol. Published online August 01, 2024. doi:10.1001/jamaoncol.2024.2503