Regular aspirin use at or after age 70 was associated with significantly reduced risk of colorectal cancer (CRC), but only in those who were already taking aspirin before turning 70, according to pooled data from two large cohorts of U.S. health professionals.
After adjustment for other risk factors, regular use was associated with a hazard ratio (HR) of 0.80 (95% CI 0.72-0.90) compared with non-regular use, reported Andrew T. Chan, MD, MPH, of Harvard Medical School and Massachusetts General Hospital in Boston.
As shown in their study online in JAMA Oncology, this inverse association was evident, however, only among individuals who initiated aspirin use before age 70 (HR 0.80, 95% CI 0.67-0.95). Commencing use at or after 70 had no significant association with a lower risk of CRC (HR 0.92, 95% CI 0.76-1.11).
The findings support recommendations to continue prophylactic aspirin use after age 70 if commenced before but not afterwards, the team said. “Taken together with the results of the ASPREE [Aspirin in Reducing Events in the Elderly] 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.”
The randomized controlled ASPREE trial found that after 4.7 years of follow-up, healthy older people taking aspirin had higher all-cause mortality compared with those on placebo, an increase largely attributable to death from cancer. The results also showed that low-dose aspirin boosted the risk of serious gastrointestinal bleeds in elderly individuals by 60% overall and by 87% for upper GI bleeds.
The new study included 94,540 participants — 67,233 women from the Nurses’ Health Study (NHS 1980-2014) and 27,313 men from the Health Professionals’ Follow-up Study (HPFS 1986-2014) who had reached the age of 70. Both cohorts were more than 90% white, and mean ages were 76.4 (NHS) and 77.7 (HPFS).
Over a total of 996,463 person-years of follow-up, there were 1,431 incident cases of CRC, the researchers reported. Compared with non-users of aspirin, participants in both cohorts who regularly used aspirin at or after age 70 were more likely to be older; to be current or past smokers; to have previously had a colonoscopy; and to have hypertension, diabetes, or hyperlipidemia.
The team noted that the results were consistent after adjustment for use of cholesterol-lowering drugs, hyperlipidemia, hypertension, and cardiovascular disease. In users who had started taking aspirin before age 70, the inverse association also held after further adjustment for duration of aspirin use before age 70 (pooled HR 0.81, 95% CI 0.70-0.95).
Asked for his perspective, Brooks D. Cash, MD, chief of the Division of Gastroenterology, Hepatology, and Nutrition at the University of Texas Health Science Center at Houston, who was not involved with the research, said the benefit of aspirin for decreasing CRC has been shown in other studies to be consistently modest and appears to accrue with prolonged use, and this analysis appears to confirm these observations.
He noted that the risk of adverse effects, even with low-dose aspirin, such as peptic ulcer disease and gastrointestinal bleeding, are magnified in patients over age 65. In addition to other limitations, the overwhelming majority of participants were Caucasian, “so any conclusions from this study should not be overstated as inclusive of all ethnicities,” Cash told MedPage Today. “Several non-Caucasian ethnicities have been shown to have an increased risk of CRC, and we do not know the effects of regular aspirin use in these different patient groups.”
He added that the findings should not be interpreted as supporting chemoprevention with aspirin for CRC “as a solely sufficient strategy to meaningfully reduce the incidence and mortality attributable to CRC.”
Rather, aspirin chemoprevention, given that it appears to convey a small benefit when initiated at a younger age, should be combined with healthy dietary habits, maintenance of ideal body weight, avoidance or cessation of tobacco use, and regular application of evidence-based CRC screening examinations such as fecal occult blood testing or colonoscopy, Cash said. “The age at which to stop aspirin for chemoprevention of CRC also remains unknown, and, based on current knowledge, this decision should be individualized.”
Regarding the age differences, Chan and co-authors noted that substantial evidence suggests that a benefit of aspirin for CRC requires at least 5 to 10 years of use, and the benefit data have mostly been based on studies of middle-aged adults.
The U.S. Preventive Services Task Force currently recommends low-dose aspirin prophylaxis for CRC in individuals with a 10-year cardiovascular risk of greater than 10%. In the absence of evidence supporting a recommendation for those in the over-70 age category, Chan and co-authors therefore undertook the two-cohort study.
In addition, they explained, there is a biologically plausible basis for the lack of outcome of aspirin on CRC when initiated at an older age. Growing evidence suggests that cancers arising in older adults may have a differential mechanistic basis compared with those in younger individuals, the team noted. For example, aging is associated with alterations in DNA methylation, which may affect cancer susceptibility.
In addition, CRC in older people arises more commonly on the right side of the colon, and the tumors have a higher prevalence of specific molecular changes such as BRAF and other variations.
“Further studies to elucidate the biologic mechanisms of aspirin according to age are warranted,” Chan and co-authors wrote.
Study limitations, the team said, included that it was not as definitive as a randomized controlled trial would be; that it was a post-hoc analysis and therefore not specifically powered to evaluate the association of CRC with aspirin initiated in older age; that even such a large study had limited ability to examine the association in specific subgroups, particularly according to different ages at initiation; and that the data from the two cohorts were based on self-reported questionnaires even though completed by trained healthcare professionals.
The study was supported by the Nurses’ Health Study and the Health Professionals Follow-up Study, Cancer Research UK, and the National Institutes of Health, and also received support from the Bau Tsu Zung Bau Kwan Yeu Hing Research and Clinical Fellowship, the Douglas Gray Woodruff Chair Fund, the Guo Shu Shi Fund, the Anonymous Family Fund for Innovations in Colorectal Cancer, the Project P Fund, the George Stone Family Foundation, and Massachusetts General Hospital.
Chan reported grants from the National Institutes of Health, the National Cancer Institute, Stand Up to Cancer, and the Crohn’s and Colitis Foundation, as well as personal fees from Bayer, Pfizer, and Boehringer Ingelheim outside of the study; several co-authors also reported various disclosures.
Cash disclosed no conflicts of interest relevant to his comments.