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Daily Aspirin Does Not Lower Colorectal Cancer Risk When Started After Age 70

JHOP - June 2021 Vol 11, No 3 - From the Literature
COMMENTARIES by Robert J. Ignoffo, PharmD, FHOPA, FASHP, FCSHP
Clinical Professor Emeritus, University of California, San Francisco; Professor Emeritus, Touro University–California, Mare Island, Vallejo, CA
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BACKGROUND: Regular aspirin use is considered the best chemoprevention strategy to reduce colorectal cancer (CRC) risk in middle-aged adults.1-3 This supported the US Preventive Services Task Force’s (USPSTF) recommendation of daily aspirin for CRC prophylaxis in adults aged 50 to 59 years and certain cardiovascular risk factors.4 The USPSTF, however, also recommends aspirin use in people aged ≥70 years, but the evidence for this is inconsistent. Recent data from the ASPREE clinical trial of healthy adults aged ≥70 years showed that daily low-dose aspirin did not reduce CRC risk,5 suggesting that at some point, aspirin may no longer provide protection against CRC, but no evidence indicated what that age was. This led researchers to examine the association of aspirin use and CRC risk in adults aged ≥70 years.

METHODS: This new prospective cohort study by Guo and colleagues was based on a pooled analysis of data from 2 large US cohort studies—the Nurses’ Health Study (1980-2014) and the Health Professionals Follow-up Study (1986-2014). These 2 studies included 94,540 adults who used aspirin for >30 years, providing a unique opportunity to examine aspirin use across mid- and late adulthood and the risk for CRC. The study’s primary end point was the link between incident CRC and use of aspirin in people aged ≥70 years.

RESULTS: Among the participants (mean age, 76.4 years for women, 77.7 years for men), 1413 incident cases of CRC were found during >996,463 person-years of follow-up. After adjusting for other risk factors, regular users of aspirin had a significantly lower risk of CRC at age ≥70 years versus nonregular users (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.72-0.90), but only among those who initiated regular aspirin use before age 70 years (HR, 0.80; 95% CI, 0.67-0.95). By contrast, people who started regular aspirin use only at age ≥70 years did not have reduced CRC risk with aspirin use (HR, 0.92; 95% CI, 0.96-1.11).

“Taken together with the results of the ASPREE trial, these findings suggest that initiation of aspirin use at an older age for the sole purpose of primary prevention of CRC should be discouraged,” concluded the researchers. “However, our findings appear to support recommendations to continue aspirin use if initiated at a younger age. Further studies to elucidate biologic mechanisms of aspirin according to age are warranted.”

  1. Drew DA, Cao Y, Chan AT. Aspirin and colorectal cancer: the promise of precision chemoprevention. Nat Rev Cancer. 2016;16(3):173-186.
  2. Chapelle N, Martel M, Toes-Zoutendijk E, et al. Recent advances in clinical practice: colorectal cancer chemoprevention in the average-risk population. Gut. 2020;69(12):2244-2255.
  3. Drew DA, Chan AT. Aspirin in the prevention of colorectal neoplasia. Annu Rev Med. 2020;72.
  4. Bibbins-Domingo K; U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016;164(12):836-845.
  5. McNeil JJ, Nelson MR, Woods RL, et al; for the ASPREE Investigator Group. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med. 2018;379(16):1519-1528.

Source: Guo CG, Ma W, Drew DA, et al. Aspirin use and risk of colorectal cancer among older adults. JAMA Oncol. 2021;7:428-435.

Commentary by Robert J. Ignoffo

Additional results from this study by Guo and colleagues are also noteworthy, including that when low-dose aspirin was taken for 5 years or more before age 70 years, aspirin was protective of CRC (pooled HR, 0.76; 95% CI, 0.59-0.98). By contrast, if aspirin was used for less than 5 years before age 70 years, no benefit was observed in preventing CRC (pooled HR, 1.00; 95% CI, 0.77-1.30).

A major point that was not mentioned in the discussion of the current study is related to the gastrointestinal adverse events associated with aspirin. In the ASPREE trial of primary prevention of cardiovascular disease, which included 19,114 persons aged ≥70 years, low-dose aspirin therapy increased upper gastrointestinal bleeding (HR, 1.87; 95% CI, 1.32-2.66), without leading to significant cardiovascular benefit.1

The current study by Guo and colleagues discussed here is an important retrospective analysis about the role of aspirin in preventing CRC in the elderly. Based on these results, it is reasonable to recommend that persons older than age 70 years do not gain benefit in using aspirin for the prevention of CRC or cardiovascular events.

  1. McNeil JJ, Nelson MR, Woods RL, et al; for the ASPREE investigator group. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med. 2018;379:1519-1528.
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