Effect of Aspirin on Disability-free Survival in the Healthy Elderly

Abstract

Background: Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.

Methods: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end point was a composite of death, dementia, or persistent physical disability. Secondary end points reported in this article included the individual components of the primary end point and major hemorrhage.

Results: A total of 19,114 persons with a median age of 74 years were enrolled, of whom 9525 were randomly assigned to receive aspirin and 9589 to receive placebo. A total of 56.4% of the participants were women, 8.7% were nonwhite, and 11.0% reported previous regular aspirin use. The trial was terminated at a median of 4.7 years of follow-up after a determination was made that there would be no benefit with continued aspirin use with regard to the primary end point. The rate of the composite of death, dementia, or persistent physical disability was 21.5 events per 1000 person-years in the aspirin group and 21.2 per 1000 person-years in the placebo group (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; P=0.79). The rate of adherence to the assigned intervention was 62.1% in the aspirin group and 64.1% in the placebo group in the final year of trial participation. Differences between the aspirin group and the placebo group were not substantial with regard to the secondary individual end points of death from any cause (12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group), dementia, or persistent physical disability. The rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs. 2.8%; hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001).

Conclusions: Aspirin use in healthy elderly persons did not prolong disability-free survival over a period of 5 years but led to a higher rate of major hemorrhage than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).

Conflict of interest statement

Dr. Nelson reports receiving travel support from Bayer and fees for serving on an advisory board from Sanofi; Dr. Shah, receiving fees for serving as site subinvestigator for a clinical trial, paid to his institution, from Eli Lilly, Lundbeck, and Novartis Pharmaceuticals and fees for serving as site investigator for a clinical trial, paid to his institution, from Genentech, Merck, Navidea Biopharmaceuticals, and Takeda Development Center Americas; Dr. Tonkin, receiving grant support, lecture fees, and fees for serving on an advisory board from Bayer and lecture fees from Amgen and Pfizer; and Dr. Donnan, serving on advisory panels for AstraZeneca, Bayer, Boehringer Ingelheim, Merck Sharpe & Dohme, Pfizer, and Servier. No other potential conflict of interest relevant to this article was reported.

Figures

Figure 1.. Randomization, Intervention, and Follow-up.

The most common reasons for exclusion from the trial were a history of cardiovascular disease, an adherence rate of less than 80% during the 4-week placebo run-in period, a Modified Mini–Mental State Examination score of less than 78 (on a scale from 0 to 100, with higher scores indicating better function), a score of 4 or 5 for any one of the six basic activities of daily living (bathing, dressing, toileting, transferring, walking, and feeding) on the Katz Index of Independence in Activities of Daily Living (scores for each activity range from 1 [no difficulty] to 5 [unable to do]; a score of 4 indicates severe difficulty in performing the activity), a low hemoglobin level, high blood pressure, or the opinion of the general practitioner or primary care physician. Participants could have more than one reason for ineligibility. For participants who withdrew from the trial, all the information up to the point of withdrawal was included in the analyses. Vital status was obtained in all the participants who were lost to follow-up or withdrew consent.

Figure 2.. Cumulative Incidence of the Primary Composite End Point.

Shown is the cumulative incidence of the primary composite end point (death from any cause, dementia, or persistent physical disability) according to trial group. First events that counted toward the primary end point during the trial included 911 deaths, 549 cases of dementia, and 375 cases of persistent physical disability. The graph stops at year 6 because only a small number of participants (44 in the aspirin group and 43 in the placebo group) reached year 7. The inset shows the same data on an enlarged y axis.

Figure 3.. Cumulative Incidence of Death, Dementia, and Persistent Physical Disability.

Shown are the cumulative incidences of all events of death, dementia, and persistent physical disability that were observed during the trial. The 95% confidence intervals were not adjusted for multiple comparisons. Insets show the same data on an enlarged y axis.