Aspirin, cardiovascular events, and major bleeding in older adults: extended follow-up of the ASPREE trial

Abstract

Background and aims: Guidelines recommend against routine initiation of low-dose aspirin in older adults for primary prevention of atherosclerotic cardiovascular disease events. This study aimed to estimate long-term and post-trial effects of aspirin on major adverse cardiovascular events (MACE) and major haemorrhage using extended follow-up of participants from the ASPREE trial.

Methods: In-trial (2010-17) and post-trial (2017-22) data were analysed. At enrolment, participants were aged ≥70 years (≥65 years for US minorities) without prior cardiovascular events, dementia, or independence-limiting physical disability. Randomization was to daily low-dose aspirin or matching placebo for the 4.7 years of the trial.

Results: Of the 19 114 participants randomized (9525 aspirin, 9589 placebo), 15 668 without in-trial MACE consented to post-trial follow-up. No long-term benefit of randomization to aspirin was observed for MACE for the entire in-trial and post-trial period [hazard ratio (HR) 1.04, 95% confidence interval (CI) .94, 1.15]. However, during the post-trial period (median 4.3 years), there was a higher rate of MACE (HR 1.17, 95% CI 1.01, 1.36) in those randomized to aspirin compared with placebo. Over the entire period, a higher rate of major haemorrhage was observed in the randomized aspirin group compared with placebo (HR 1.24, 95% CI 1.10, 1.39).

Conclusions: The present study provides novel evidence concerning long-term MACE and haemorrhage following aspirin use in initially healthy older adults. The finding of no long-term MACE benefit needs to be considered in clinical decision-making if aspirin is being considered for use in this context.

Keywords: Aspirin; Clinical trial; Coronary artery disease; Haemorrhage; Major adverse cardiovascular events; Observational follow-up; Stroke.

Structured Graphical Abstract

Effects of aspirin on cardiovascular events and major haemorrhage in ASPREE extended follow-up. CVD, cardiovascular disease; MACE, major adverse cardiovascular events; ASPREE, ASPirin in Reducing Events in the Elderly.

Figure 1

Aspirin exposure pre-, in-, and post-trial by country and randomised arm in ASPREE. The annual visits are presented relative to the end of the trial with participants censored at the time of a major adverse cardiovascular event. Aspirin exposure was defined as 15% or more adherence to study aspirin pills (for those randomized to aspirin only), or reporting aspirin use on two or more days per week in questionnaires, or recording aspirin in concomitant medications list

Figure 2

Forest plot of hazard ratios estimating long-term effects of aspirin on major adverse cardiovascular events during the entire period of the in-trial and post-trial. Characteristics were ascertained at trial baseline

Figure 3

Cumulative incidence of major adverse cardiovascular events. Participants were randomized at various dates during the ASPREE clinical trial (March 2010–December 2014). Consequently, 13 June 2017 does not represent the same time point since randomization for each participant, ranging from 2.5 to 7.3 years

Figure 4

Cumulative incidence of major haemorrhage. Participants were randomized at various dates during the ASPREE clinical trial (March 2010–December 2014). Consequently, 13 June 2017 does not represent the same time point since randomization for each participant, ranging from 2.5 to 7.3 years