Subgroup analysis of the ASPirin in Reducing Events in the Elderly randomized clinical trial suggests aspirin did not improve outcomes in older adults with chronic kidney disease

Abstract

The role of aspirin for primary prevention in older adults with chronic kidney disease (CKD) is unclear. Therefore, post hoc analysis of the randomized controlled trial ASPirin in Reducing Events in the Elderly (ASPREE) was undertaken comparing 100 mg of enteric-coated aspirin daily against matching placebo. Participants were community dwelling adults aged 70 years and older in Australia, 65 years and older in the United States, all free of a history of dementia or cardiovascular disease and of any disease expected to lead to death within five years. CKD was defined as present at baseline if either eGFR under 60mL/min/1.73m² or urine albumin to creatinine ratio 3 mg/mmol or more. In 4758 participants with and 13004 without CKD, the rates of a composite endpoint (dementia, persistent physical disability or death), major adverse cardiovascular events and clinically significant bleeding in the CKD participants were almost double those without CKD. Aspirin's effects as estimated by hazard ratios were generally similar between CKD and non-CKD groups for dementia, persistent physical disability or death, major adverse cardiovascular events and clinically significant bleeding. Thus, in our analysis aspirin did not improve outcomes in older people while increasing the risk of bleeding, with mostly consistent effects in participants with and without CKD.

Keywords: aspirin; bleeding; cardiovascular events; chronic kidney disease; elderly; randomized clinical trial.

Figure 1. Inclusion of participants in analysis and chronic kidney disease (CKD) status.

*A total of 983 missing urine albumin:creatinine ratio (UACR); an additional 362 missing estimated glomerular filtration rate (eGFR); 104 missing both.

Figure 2

Cumulative incidence in the aspirin and placebo groups of (a) dementia, persistent physical disability or death; (b) major adverse cardiovascular events (MACE: coronary heart disease death, nonfatal myocardial infarction, or nonfatal ischemic stroke), and (c) clinically significant bleeding. CKD, chronic kidney disease.

Figure 3

Cumulative incidence in the aspirin and placebo groups of (a) myocardial infarction, (b) ischemic stroke, (c) all-cause mortality, and (d) cardiovascular mortality. CKD, chronic kidney disease.