Effect of Aspirin on Cancer Incidence and Mortality in Older Adults

Abstract

Background: ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality.

Methods: 19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records.

Results: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64).

Conclusions: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group.

Figure 1.

Cumulative incidence of first incidence of solid tumor cancer, by stage and treatment group.

Figure 2.

Cumulative incidence of cancer-related death following a first presentation of localized or metastatic cancer. Panel (A) shows localized cancer, and panel (B) shows metastatic cancer. Time is from random assignment to the occurrence of death following the cancer event.

Figure 3.

Forest plots of solid tumor cancer incidence and mortality by subgroup. Solid tumor cancer incidence is shown (A) and mortality is shown (B). Subgroups are classed from baseline (enrollment) and include age in years, BMI (in kg/m²), prior cancer history, and family cancer history. For 'Other', within the ethnicity/race subgroup, all events occurred in the aspirin arm (ie, no events in the placebo arm), and thus, HR cannot be estimated. Not all participants were asked about cancer-related medical screening (questionnaire introduced late in recruitment, 2013). AUS = Australian; BMI = body mass index; CI = confidence interval; HR = hazard ratio; pts = participant; NA = not applicable.