Another Negative Study of Aspirin for Primary Prevention

In two recent primary prevention studies — one conducted in nondiabetic patients with cardiovascular risk factors and the other in type 2 diabetic patients — aspirin raised risk for serious bleeding while conferring no or minimal cardiovascular (CV) benefit (NEJM JW Gen Med Oct 1 2018 and Lancet 2018 Aug 26; [e-pub]; NEJM JW Gen Med Oct 1 2018 and N Engl J Med 2018 Aug 26; [e-pub]). Now, in a third study (ASPREE) researchers have examined preventive aspirin use in “healthy elderly” community-dwelling people in the U.S. and Australia. The main enrollment criterion was age (≥70 for whites; ≥65 for blacks and Hispanics). People with known CV disease, substantial cognitive or physical disability, or high risk for bleeding were excluded, but most participants had one or more CV risk factors.

About 19,000 people (median age, 74) were randomized to receive aspirin (100 mg) or placebo daily. During median follow-up of 4.7 years, the following outcomes (published in three separate papers) were noted:

• Incidence of the primary endpoint (i.e., death, dementia, or persistent physical disability) was virtually identical (≈10%) in aspirin and placebo groups.

• All-cause mortality was slightly higher with aspirin than placebo (5.9% and 5.2%). The difference was entirely attributable to significantly more cancer deaths with aspirin (3.1% vs. 2.3%).

• There were no differences between groups in any composite or individual CV endpoint. No subgroup (including people with multiple risk factors) derived CV benefit from aspirin.

• Major hemorrhage occurred significantly more frequently with aspirin than with placebo (3.8% vs. 2.8%).