A team of researchers has suggested that low-dose aspirin was not associated with a reduced incidence of cancer in older adults, but was associated with an increased risk of dying of cancer, according to a cohort study of participants from the randomised ASPREE trial.
Among more than 19 000 adults with a mean age of 75, cancer incidence during 10 years of follow-up was almost identical in patients who used aspirin and those who did not (HR 0.98, 95% CI 0.92-1.05), reports MedPage Today.
The risk of dying of cancer was 15% higher in patients who took low-dose aspirin.
An analysis of 14 907 surviving participants who continued follow-up in the extension phase of the randomised ASPREE trial showed no difference in cancer incidence or cancer mortality, reported Suzanne Orchard, PhD, of Monash University in Melbourne, Australia, and colleagues in JAMA Oncology.
Despite the size of the study and the extended duration of follow-up, the results do not rule out the possibility of a benefit from low-dose aspirin, said Orchard.
“It is hard to say anything definitive, especially since there are not that many studies conducted in older persons," she told MedPage Today. “The earlier studies have found that cancer incidence benefits can take up to 10 to 15 years to manifest, and so longer follow-up of the current ASPREE cohort is warranted, to see if the associations between aspirin and cancer incidence and mortality change over time.
“We would like to see whether aspirin can impact specific subgroups differently, and earlier work in our group has indicated this may be the case,” she noted.
“Studies exploring the mechanism of action in older people would also be valuable – for example, those with certain gene variants. There have been some reports of individuals with PI3K gene variations responding differently to aspirin. So, genetic profiling of the cancers from those in the aspirin arm versus the placebo arm may shed some light on the mechanism.”
The data did show a reduced incidence of melanoma in the aspirin arm, and an increased incidence of brain cancer, two findings that require further investigation, Orchard said.
Early randomised clinical trials of aspirin and cancer, mostly involving middle-age adults, showed a reduced risk of cancer and lower cancer-related mortality, particularly for colorectal cancer (CRC).
The Women’s Health Study provided additional evidence of a favourable effect of aspirin on CRC.
More recent studies showed that starting aspirin at an older age had no effect on cancer outcomes or increased rates of malignancy. However, follow-up in these studies was too brief for a preventive effect on cancer to emerge, the authors noted in their introduction.
The ASPREE trial comprised a randomised phase with a median follow-up of 4.7 years and a five-year extension phase (ASPREE-XT) to examine long-term impact of prior randomisation to aspirin or placebo.
Conducted in Australia and the US, the trial enrolled patients aged 70 and older (65 or older for black and Latino patients in the US) who were randomised to low-dose aspirin (100 mg/day) or placebo. Eligible patients were free of cardiovascular disease, dementia and independence-limiting physical disability.
The randomised phase enrolled patients from 2010-2014 with follow-up to 2017. ASPREE-XT followed study participants from 2018-2024.
For the overall population, 3 448 cancers and 1 173 cancer-related deaths occurred during 10 years of follow-up (median 8.6 years).
New cancers were almost evenly distributed between the two arms, 1 701 in the aspirin group and 1 747 in the placebo group.
Incidence of localised, metastatic, and haematologic malignancies was also similar between the two groups.
The aspirin arm had 623 deaths versus 550 in the placebo arm, resulting in a hazard ratio of 1.15 (95% CI 1.03-1.29).
During ASPREE-XT, 689 cancers occurred in the patients originally randomised to aspirin versus 762 in the placebo group, a non-significant 9% difference (95% CI 0.82-1.01). Each group had 188 cancer-related deaths (HR 1.02, 95% CI 0.83-1.25).
The incidence and mortality for colorectal cancer, a topic of multiple studies of cancer prevention with aspirin, were almost identical in the overall and ASPREE-XT analyses.
Over the entire duration of follow-up, fewer cases of melanoma occurred in the aspirin arm (159 vs 209, HR 0.77, 95% CI 0.62-0.94). The difference persisted in the analysis limited to ASPREE-XT participants (71 vs 101, HR 0.71, 95% CI 0.53-0.96).
During the randomised phase of the investigation, significantly more patients in the aspirin group developed brain cancer, though absolute numbers were small (HR 1.96, 95% CI 1.05-3.65).
Additionally, the aspirin group had a higher mortality for combined rare cancers (HR 2.09, 95% CI 1.21-3.61).
“The results are difficult to be certain of due to low sample sizes,” said Orchard.
See more from MedicalBrief archives:
Brain bleed risk upped by daily aspirin – second ASPREE trial analysis
Aspirin reduces cardiovascular events in elderly with raised Lp(a) – ASPREE analysis
Aspirin reduces cardiovascular events in elderly with raised Lp(a) – ASPREE analysis