No Modulation of the Effect of Aspirin by Body Weight in Healthy Older Men and Women
Authors: Robyn L. Woods, Galina Polekhina, Rory Wolfe, Mark R. Nelson, Michael E. Ernst, Christopher M. Reid, Raj C. Shah, Jessica E. Lockery, Suzanne G. Orchard, Anne M. Murray, John J. McNeil
Journal: Circulation (2020)

aging ◼ aspirin ◼ body weight A recent meta-analysis 1 of individual patient data from several randomized, controlled trials evaluating aspirin for the prevention of primary or secondary cardiovascular events found that the protective effect of low-dose aspirin (≤100 mg) was limited to individuals weighing <70 kg, driven by lean body mass (LBM) but not body mass index (BMI). 1Given the limited number of people ≥70 years of age who were included in the meta-analysis 1 and calls for validation of these findings, 2,3 we investigated whether body habitus modulated the efficacy of aspirin in a post hoc analysis of the ASPREE trial (Aspirin in Reducing Events in the Elderly). 4SPREE randomized 19 114 older participants to daily 100-mg enteric-coated aspirin (9525) or matched placebo (9589) and followed them up for a median of 4.7 years for disability-free survival and other clinical outcomes. 4Trial participants were community-dwelling Australian (16 703) and US (2411) men and women who were ≥70 years of age at enrollment or ≥65 years of age for US blacks and Hispanics.Individuals were required to be free of any chronic illnesses likely to limit survival to <5 years and free of documented cardiovascular or cerebrovascular disease or high risk of bleeding. 4Anthropometric data, including body weight, height (deriving BMI as weight/height 2 and LBM from sex-specific weight and height 1 ), and waist circumference, were obtained for each participant.ASPREE had multiple Institutional Ethics Review Committee approvals in Australia and the United States.All ASPREE participants provided informed consent.ASPREE was registered at ClinicalTrials.gov(https://www.clinicaltrials.gov;NCT01038583).Major adverse cardiovascular events 4 included coronary heart disease fatalities; other coronary, rapid cardiac, and sudden cardiac but excluding cardiac failure deaths; nonfatal myocardial infarction; and fatal and nonfatal ischemic stroke.Major hemorrhage end points 4 included hemorrhagic stroke, subarachnoid hemorrhagic stroke, and nonstroke clinically significant bleeding: intracranial, gastrointestinal, or other sites.End points were adjudicated by blinded clinical experts.End points were analyzed with Cox proportional hazard models by treatment (aspirin versus placebo) and body size groups in all participants and by sex.Of the ASPREE participants weighing <70 kg, 1054 were men and 5374 were women, leaving 7258 men and 5375 women ≥70 kg.Anthropometric measures at baseline were included in these models either as (1) dichotomized variables with cutoffs for body weight (70 kg; for direct comparison with meta-analysis findings 1 ), BMI (25 kg/m 2 ) to identify overweight and above, 4 waist circumference separated at 88 cm for women and 102 cm for men according to high disease risk, 5 and LBM 1 at 45 kg for women and 55 kg for men or (2) continuous variables with an assumption of linear relationship with log hazard.The proportional hazards assumption was satisfied on checking of Schoenfeld residuals.These were post hoc exploratory analyses, and P values were not adjusted for multiple comparisons.