Aspirin, cardiovascular events, and major bleeding in older adults: extended follow-up of the ASPREE trial
Rory Wolfe, Jonathan Broder, Zhen Zhou, Anne M. Murray, Joanne Ryan, Andrew T. Chan, Mark Nelson, Robyn L. Woods, Michael E. Ernst, Suzanne G. Orchard, Brenda Kirpach, Christopher M Reid, Raj C. Shah, Nigel Stocks, Karen L. Margolis, Franz–Josef Neumann, Michelle Wilson, Sharyn M. Fitzgerald, Suzanne E. Mahady, Erica M. Wood, Shara Ket, Charles B. Eaton, Peter J. Hand, Mobin Malik, Walter P. Abhayaratna, P. Venkataraman, Peter Chan, Geoffrey Cloud, Geoffrey A. Donnan, Jeff D. Williamson, Andrew Tonkin
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.