Low-dose aspirin's effects on survival may come with caveats
A trial was stopped early after researchers determined that continued aspirin use appeared to yield no benefit.
Low-dose aspirin was not associated with prolonged survival but was associated with higher rates of major hemorrhages and cancer, according to new research.
In the Aspirin in Reducing Events in the Elderly (ASPREE) study, researchers randomly assigned 19,114 community-dwelling people in the U.S. and Australia who were ages 70 years and older and had no cardiovascular disease, dementia, or physical disability to receive 100 mg of aspirin (n=9,525) or placebo (n=9,589) daily for a five-year period. However, the trial was stopped at 4.7 years after researchers determined that continued aspirin use appeared to yield no benefit. Results of the study were published as three separate papers on Sept. 16 by the New England Journal of Medicine.
In the first study, aspirin in healthy elderly people was not associated with prolonged disability-free survival over a five-year period but was associated with higher rates of major hemorrhages compared to placebo. The primary end point was a composite of death, dementia, or persistent physical disability, and the secondary end point included individual components of the primary end point as well as major hemorrhage.
The rate of the composite end point was 21.5 events per 1,000 person-years in the aspirin group and 21.2 per 1,000 person-years in the placebo group (hazard ratio [HR], 1.01; 95% CI, 0.92 to 1.11; P=0.79). Differences between groups for the secondary end point were not substantial. The rate of death from any cause was 12.7 events per 1,000 person-years in the aspirin group and 11.1 events per 1,000 person-years in the placebo group. Patients in the aspirin group had a higher rate of major hemorrhage than those in the placebo group (3.8% vs. 2.8%; HR, 1.38; 95% CI, 1.18 to 1.62; P<0.001).
This trial focused on integrating the benefits and harms of aspirin as a preventive agent in an otherwise healthy elderly population, the authors wrote. “This trial did not directly address the question of whether healthy older persons who have been using aspirin for primary prevention should continue or discontinue its use,” they noted.
The second trial, which assessed the association between aspirin and cardiovascular events and bleeding, concluded that aspirin was linked to a significantly higher risk for major hemorrhage but not a lower risk of cardiovascular disease.
In this study, fatal coronary heart disease was defined as death from myocardial infarction, sudden cardiac death, or any death due to coronary heart disease. A secondary end point was major hemorrhage, defined as a composite of hemorrhagic stroke, symptomatic intracranial bleeding, or clinically significant extracranial bleeding that led to transfusion, hospitalization, prolongation of hospitalization, surgery, or death.
The rate of major adverse cardiovascular events was 7.8 per 1,000 person-years in the aspirin group and 8.8 per 1,000 person-years in the placebo group (HR, 0.89; 95% CI, 0.77 to 1.03). Rates of infarction, stroke, fatal cardiovascular disease, and hospitalization were similar between treatment and control groups, and rates of the secondary events likewise did not differ significantly (10.7 events per 1,000 person-years of follow-up vs. 11.3 events per 1,000 person years; HR, 0.95; 95% CI, 0.83 to 1.08).
The authors noted that interpretation of these results should consider the lower-than-expected rate of cardiovascular disease among the trial participants, adding “ … the use of low-dose aspirin resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo.”
The third study on all-cause mortality focused on the result from the first trial that a higher rate of death from any cause was reported among patients assigned to aspirin than among the placebo-control group.
There were 1,052 deaths (5.5%) during the study. As previously noted, there were 12.7 deaths per 1,000 person-years in the aspirin group and 11.1 per 1,000 person-years in the control group (HR, 1.14; 95% CI 1.01 to 1.29). Cancer was the major contributor to mortality, causing 1.6 excess deaths per 1,000 person-years and affecting 3.1% of the aspirin group and 2.3% of the placebo group (HR, 1.31; 95% CI, 1.10 to 1.56). The risk of cancer-related death was higher in the aspirin group than in the placebo group (6.7 events per 1,000 person-years vs. 5.1 events per 1,000 person-years). Nearly half of all deaths (49.6%) in the study were due to cancer, followed by 19.3% due to cardiovascular disease (including ischemic stroke) and 5.0% due to major hemorrhage (including hemorrhagic stroke).
The authors noted that other trials of aspirin for primary prevention did not note these potential effects on mortality. “In the context of previous studies, this result was unexpected and should be interpreted with caution,” the authors wrote.